<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01694108</url>
  </required_header>
  <id_info>
    <org_study_id>EudraCT2010-021979-85</org_study_id>
    <nct_id>NCT01694108</nct_id>
  </id_info>
  <brief_title>Bacille Calmette Guérin Immunisation at Birth and Childhood Morbidity in Danish Children.</brief_title>
  <official_title>Bacille Calmette Guérin Immunisation at Birth and Childhood Morbidity in Danish Children. A Prospective, Randomised, Clinical Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lone Graff Stensballe</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hvidovre University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Kolding Sygehus</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Danish National Research Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Research Center for Vitamins and Vaccines (CVIVA)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Rigshospitalet, Denmark</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In high-income societies the use of health care and medication is steadily increasing.&#xD;
      Children have high morbidity, many visits at the general practitioner, an increasing number&#xD;
      of hospitalisations, and an increasing use of medication. And, when children are ill, someone&#xD;
      has to stay home to care for them. An un-explained global increase in the incidence of the&#xD;
      allergic diseases eczema, wheezing, asthma and allergies means that 25% of high-income&#xD;
      populations are affected. Cheap preventive measures are highly warranted. Recent studies have&#xD;
      shown a positive, non-specific effect of early Bacille Calmette Guérin (BCG) immunisation on&#xD;
      neonatal mortality in low-income countries and suggested a positive, non-specific effect on&#xD;
      allergic disease in high-income countries. &quot;Non-specific&quot; means that the vaccine effect goes&#xD;
      beyond prevention of the targeted disease, i.e. the BCG vaccine benefits the health status of&#xD;
      the immunised individual in ways unrelated to protection against tuberculosis (TB). For&#xD;
      instance, in a recent randomised trial in West Africa the investigators showed that the BCG&#xD;
      vaccine at birth was safe in low birth weight (LBW) infants and significantly reduced&#xD;
      neonatal mortality in these children, with a significant long-lasting effect on infant&#xD;
      mortality in the smallest newborns with a birth weight &lt;1.5 kg. There is an urgent need to&#xD;
      explore the huge potential of the BCG's beneficial immune-stimulatory effects among children&#xD;
      in high-income populations.&#xD;
&#xD;
      Therefore, the investigators will carry out a large prospective randomised clinical trial in&#xD;
      Denmark primarily designed to test the hypothesis that infants who get the BCG vaccine at&#xD;
      birth experience 20% fewer hospitalisations during early childhood.&#xD;
&#xD;
      Secondary outcomes&#xD;
&#xD;
        1. To test the hypothesis that infants who get the BCG vaccine at birth are prescribed less&#xD;
           antibiotics during early childhood than non-BCG-immunised infants.&#xD;
&#xD;
        2. To test the hypothesis that Danish infants who get the BCG vaccine at birth develop less&#xD;
           eczema, asthmatic bronchitis/wheeze and food allergy at 3 and 12 months of age:&#xD;
           self-reported, diagnosed by a physician, or found at clinical examination; and are&#xD;
           prescribed less anti-eczema/asthma/allergy medication during early childhood than&#xD;
           non-BCG-immunised infants.&#xD;
&#xD;
        3. To test the hypothesis that infants who receive the BCG at birth respond in paraclinical&#xD;
           measures: Specific IgE, thymic gland size, leucocyte count and differentiation, monocyte&#xD;
           memory, cytokine profiles, and antibody titres following immunisation against&#xD;
           diphtheria, tetanus, pertussis, pneumococcus, hemophilus.&#xD;
&#xD;
        4. To test the hypothesis that infants who get the BCG vaccine at birth respond in growth&#xD;
           measures: weight, length and head circumference.&#xD;
&#xD;
        5. To test the hypothesis that infants who get the BCG vaccine at birth respond with&#xD;
           decreased morbidity: common cold, pneumonia, febrile episodes, diarrhoea and vomiting,&#xD;
           acute otitis media, febrile convulsions.&#xD;
&#xD;
        6. To test the hypothesis that premature infants with gestational age less than 37 weeks&#xD;
           who get the BCG vaccine at birth have unaffected psychomotor development measures: Ages&#xD;
           and Stages scores.&#xD;
&#xD;
        7. To test the hypothesis that infants who get the BCG vaccine at birth has unaffected&#xD;
           coverage with the subsequent vaccinations in the Child Vaccination Programme.&#xD;
&#xD;
        8. To test the above mentioned hypotheses specifically in the strata of premature and&#xD;
           low-birth-weight Danish infants.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">January 2015</completion_date>
  <primary_completion_date type="Actual">January 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>All-cause Hospitalisations</measure>
    <time_frame>0-15 months of age</time_frame>
    <description>To test that infants who get the BCG vaccine at birth experience 20% fewer hospitalisations in early childhood than non-BCG-immunised infants.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Antibiotics</measure>
    <time_frame>0-15 months of age</time_frame>
    <description>To test that infants who get the BCG vaccine at birth are prescribed less antibiotics during early childhood than non-BCG-immunised infants. Use of antibiotics was defined as one or more precriptions of systemic antibiotics (ATC groups J01, J02, J05, all subgroups inclusive).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Atopic Dermatitis</measure>
    <time_frame>13 months of age</time_frame>
    <description>To test if BCG vaccination within 7 days after birth influence the risk of atopic dermatitis defined by clinical examination at 13 months of age using &quot;scoring atopic dermatitis (SCORAD)&quot; or by parental report of physician diagnosed atopic dermatitis in the telephone interview at 13 months of age.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Specific IgE</measure>
    <time_frame>13 months of age</time_frame>
    <description>Number of participants with specific IgE (Phadiatop Infant) above the clinical cut-of level of 0.35.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Standardized Weight at 13 Months</measure>
    <time_frame>13 months of age</time_frame>
    <description>To test that infants who get the BCG vaccine at birth respond in weight.The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Psychomotor Development in Premature Infants</measure>
    <time_frame>13 months of age</time_frame>
    <description>To test that premature infants with gestational age less than 37 weeks who get the BCG vaccine at birth have unaffected psychomotor development measures: ASQ: Ages and stages questionnaire - a parent reported questionnaire that measures child psychomotor development. Total range of ASQ score: 0 to 300 points. Higher scores indicate higher level of psychomotor development.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DTaP-IPV-Hib Vaccination Coverage at 12 Months of Age</measure>
    <time_frame>13 months of age</time_frame>
    <description>To test that infants who get the BCG vaccine at birth has unaffected coverage with the subsequent 3rd diphtheria, tetanus, acellular pertussis, polio, Haemophilus influenzae type b (DTaP-IPV-Hib) vaccination scheduled to 12 months of age according to the Danish child vaccination programme. Since we did not expect all children to get their immunizations exactly at 12 months of age, the children were followed up until 13-months of age.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Standardized Weight, Length and Head Circumference of Premature Children at 13 Months</measure>
    <time_frame>13 months of age</time_frame>
    <description>The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Episodic Viral Wheeze</measure>
    <time_frame>13 months</time_frame>
    <description>Number of participants diagnosed with episodic viral wheeze by a physician and treated with anti-asthmatic medicine according to the telephone interview.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Food Allergy</measure>
    <time_frame>13 months</time_frame>
    <description>Number of participants with food allergy diagnosed by a physician and mentioned in the telephone interview at 13 months of age</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length at 13 Months of Age</measure>
    <time_frame>13months</time_frame>
    <description>To test if infants who get the BCG vaccine at birth respond in length. The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Standardized Head Circumference at 13 Months of Age</measure>
    <time_frame>13 months</time_frame>
    <description>To test if infants who get the BCG vaccine at birth respond in head circumference. The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Thymic Gland Size at 3 Months of Age</measure>
    <time_frame>3 months of age</time_frame>
    <description>To test that infants who receive the BCG at birth respond in thymic gland size defined by ultra sound examination. First, the thymus gland was identified in a horizontal scanning plane and the largest transverse diameter of the thymus was obtained. Second, in a sagittal scanning plane, the area of the largest lobe was assessed. Both measurements were obtained twice, and in case of more than 15% difference, both measurements were repeated. The mean of the two measurements were multiplied and defined as the thymic index.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Leucocyte Count 4 Days After Randomisation/Vaccination</measure>
    <time_frame>4 days after randomisation/vaccination within 7 days after birth</time_frame>
    <description>To test if infants who receive the BCG at birth respond in leucocyte count (white blood cell count) measured as geometric mean (GM) cell concentrations (GM*10^9 cells/L).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Monocyte Count 4 Days After Randomisation/Vaccination</measure>
    <time_frame>4 days after randomisation/vaccination within 7 days after birth</time_frame>
    <description>To test if infants who receive the BCG at birth respond in monocyte count measured as geometric mean (GM) cell concentrations (GM*10^9 cells/L).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interferon Gamma Response</measure>
    <time_frame>13 months of age</time_frame>
    <description>To test that infants who receive the BCG at birth respond in interferon-gamma response upon stimulation with BCG. The interferon gamma response was defined as a value above the cut-off value of 107 pg/ml.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Antibody Concentration (AC) Against Tetanus of &gt; 0.1 IU/mL</measure>
    <time_frame>13 months of age</time_frame>
    <description>To test the tetenus antibody response in BCG-vaccinated vs. non-BCG vaccinated children following routine immunisation against tetanus at 3, 5 and 12 months of age in blood samples obtained 13 months of age.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Events of Common Cold</measure>
    <time_frame>13 months of age</time_frame>
    <description>To test that Danish infants who get the BCG vaccine at birth experience less events of common cold until 13 months of age than non-BCG-immunised infants.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Events of Pneumonia</measure>
    <time_frame>13 months of age</time_frame>
    <description>To test that Danish infants who get the BCG vaccine at birth get less pneumonia at 13 months of age than non-BCG-immunised infants.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Events of Febrile Episodes</measure>
    <time_frame>13 months of age</time_frame>
    <description>To test that Danish infants who get the BCG vaccine at birth get less febrile episodes at 13 months of age than non-BCG-immunised infants.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Events With Diarrhoea and Vomiting</measure>
    <time_frame>13 months of age</time_frame>
    <description>To test that Danish infants who get the BCG vaccine at birth develop less episodes with diarrhoea and vomiting at 13 months of age than non-BCG-immunised infants.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Events of Acute Otitis Media</measure>
    <time_frame>13 months of age</time_frame>
    <description>To test that Danish infants who get the BCG vaccine at birth develop less acute otitis media at 13 months of age than non-BCG-immunised infants.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Events of Febrile Convulsions</measure>
    <time_frame>13 months of age</time_frame>
    <description>To test that Danish infants who get the BCG vaccine at birth develop less febrile convulsions at 13 months of age than non-BCG-immunised infants.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Decisional Conflict Scale Score</measure>
    <time_frame>The decisional conflict score was measured before randomisation</time_frame>
    <description>After parents having made the decision about whether to accept vaccination of their newborn through participation in The Danish Calmette Study, O'Connor's Decisional Conflict Scale was used to identify decisional conflicts. The score ranges from 0 (no decisional conflict) til 100 (maximum decisional conflict). Scores lower than 25 are associated with implementing decisions; scores exceeding 37.5 are associated with decision delay or feeling unsure about implementation; so a low score reflects a low level of doubt about the decision about participation/decline participation in the trial, and a high score reflects a high level of doubt.</description>
  </other_outcome>
  <other_outcome>
    <measure>Quality of Communication and Information</measure>
    <time_frame>2 days after the information was given</time_frame>
    <description>To test that the use of telephone and internet was acceptable in the study population using the Quality of Informed Consent (QuIC) questionnaire. The questionnaire was divided into six categories; five on study comprehension and one on satisfaction with the information process. The items in the first five categories could be answered with &quot;yes&quot;, &quot;no&quot; or &quot;do not know&quot;. The last category was rated on a 7-point Likert scale, with 1 being &quot;very dissatisfied&quot; and 7 being &quot;very satisfied&quot;. The primary outcome was the sum of the score for comprehension items and satisfaction items. Comprehension items were scored 1 point for each correct answer and 0 points for each incorrect answer. Satisfaction items were scored as rated on the 7-point Likert scale. Total score ranged from 7 to 69 points, comprehension score from 0 to 20 points and satisfaction score from 7 to 49 points. The higher score, the better comprehension and satisfaction.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">4262</enrollment>
  <condition>Prospective</condition>
  <condition>Single-blind</condition>
  <condition>Clinical</condition>
  <condition>Trial</condition>
  <condition>Intervention</condition>
  <arm_group>
    <arm_group_label>BCG-vaccine (SSI)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Children born to mothers, who have accepted to participate, will be randomised to either intervention group or to the control group at birth. Block-randomisation stratified by hospital, gender and gestational age (≥37 weeks of gestation vs. &lt; 37 weeks of gestation) will be performed electronically just before vaccination by the overall study electronic case report system (e-crf).&#xD;
Children randomised to the BCG vaccination group will receive an intradermal BCG vaccine (Statens Serum Institute &quot;CG vaccine&quot; in the standard dose 0.05 ml in the upper, lateral part of the arm of the child by a specially trained midwife or a study physician.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No Intervention</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Control children will be treated as usual, since no suitable placebo exists.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>BCG-vaccine (SSI)</intervention_name>
    <arm_group_label>BCG-vaccine (SSI)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All parents planning to give birth at Rigshospitalet, Hvidovre Hospital and Kolding&#xD;
             Hospital will receive at letter during 2nd/3rd trimester of pregnancy with information&#xD;
             on the study and be offered inclusion in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Infants born before gestational age 32 weeks and/or birth weight &lt; 1000g, infants with&#xD;
             known congenital disease, anomaly or malformation, immune deficiency and HIV, will be&#xD;
             excluded. Non-Danish speaking parents will be excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>7 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lone G Stensballe, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rigshospitalet. The Danish National Hospital in Denmark.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <state>Copenhagen Ø</state>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hvidovre Hospital</name>
      <address>
        <city>Copenhagen</city>
        <zip>2650</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kolding Sygehus</name>
      <address>
        <city>Kolding</city>
        <zip>6000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <link>
    <url>http://Calmette-studiet.dk</url>
    <description>Study home page</description>
  </link>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>September 22, 2012</study_first_submitted>
  <study_first_submitted_qc>September 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2012</study_first_posted>
  <results_first_submitted>December 3, 2015</results_first_submitted>
  <results_first_submitted_qc>December 3, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 8, 2016</results_first_posted>
  <last_update_submitted>April 26, 2017</last_update_submitted>
  <last_update_submitted_qc>April 26, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 24, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Rigshospitalet, Denmark</investigator_affiliation>
    <investigator_full_name>Lone Graff Stensballe</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>BCG Vaccine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>BCG-vaccine</title>
        </group>
        <group group_id="P2">
          <title>Control Children (no Intervention)</title>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2129"/>
                <participants group_id="P2" count="2133"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2129">100% follow-up</participants>
                <participants group_id="P2" count="2133">100% follow-up</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Baseline characteristics by allocation among the 4184 mothers in The Danish Calmette Study</population>
      <group_list>
        <group group_id="B1">
          <title>BCG-vaccine</title>
          <description>SSI strain 1331 standard dose</description>
        </group>
        <group group_id="B2">
          <title>Control Children</title>
          <description>No intervention</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="2095"/>
            <count group_id="B2" value="2089"/>
            <count group_id="B3" value="4184"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>Maternal age</description>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32.0" spread="4.6"/>
                    <measurement group_id="B2" value="31.9" spread="4.4"/>
                    <measurement group_id="B3" value="31.95" spread="4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <description>Gender of the child. In multiple births: gender of the first born child.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1003"/>
                    <measurement group_id="B2" value="985"/>
                    <measurement group_id="B3" value="1988"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1092"/>
                    <measurement group_id="B2" value="1104"/>
                    <measurement group_id="B3" value="2196"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <description>All three study sites are situated in Denmark.</description>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Denmark</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2095"/>
                    <measurement group_id="B2" value="2089"/>
                    <measurement group_id="B3" value="4184"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Premature birth</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61"/>
                    <measurement group_id="B2" value="60"/>
                    <measurement group_id="B3" value="121"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>All-cause Hospitalisations</title>
        <description>To test that infants who get the BCG vaccine at birth experience 20% fewer hospitalisations in early childhood than non-BCG-immunised infants.</description>
        <time_frame>0-15 months of age</time_frame>
        <population>Intention-to-treat</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
          </group>
          <group group_id="O2">
            <title>Control Children (no Intervention)</title>
          </group>
        </group_list>
        <measure>
          <title>All-cause Hospitalisations</title>
          <description>To test that infants who get the BCG vaccine at birth experience 20% fewer hospitalisations in early childhood than non-BCG-immunised infants.</description>
          <population>Intention-to-treat</population>
          <units>Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2129"/>
                <count group_id="O2" value="2133"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="637"/>
                    <measurement group_id="O2" value="633"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Antibiotics</title>
        <description>To test that infants who get the BCG vaccine at birth are prescribed less antibiotics during early childhood than non-BCG-immunised infants. Use of antibiotics was defined as one or more precriptions of systemic antibiotics (ATC groups J01, J02, J05, all subgroups inclusive).</description>
        <time_frame>0-15 months of age</time_frame>
        <population>Intention-to-treat</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SSI strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Antibiotics</title>
          <description>To test that infants who get the BCG vaccine at birth are prescribed less antibiotics during early childhood than non-BCG-immunised infants. Use of antibiotics was defined as one or more precriptions of systemic antibiotics (ATC groups J01, J02, J05, all subgroups inclusive).</description>
          <population>Intention-to-treat</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2129"/>
                <count group_id="O2" value="2133"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="934"/>
                    <measurement group_id="O2" value="931"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Atopic Dermatitis</title>
        <description>To test if BCG vaccination within 7 days after birth influence the risk of atopic dermatitis defined by clinical examination at 13 months of age using &quot;scoring atopic dermatitis (SCORAD)&quot; or by parental report of physician diagnosed atopic dermatitis in the telephone interview at 13 months of age.</description>
        <time_frame>13 months of age</time_frame>
        <population>This analysis includes children with follow-up data from clinical examination or telephone interview. As opposed to the register-based primary outcome, adherence to telephone-interview and clinical examination was slightly lower than 100%.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SS! strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Atopic Dermatitis</title>
          <description>To test if BCG vaccination within 7 days after birth influence the risk of atopic dermatitis defined by clinical examination at 13 months of age using &quot;scoring atopic dermatitis (SCORAD)&quot; or by parental report of physician diagnosed atopic dermatitis in the telephone interview at 13 months of age.</description>
          <population>This analysis includes children with follow-up data from clinical examination or telephone interview. As opposed to the register-based primary outcome, adherence to telephone-interview and clinical examination was slightly lower than 100%.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2052"/>
                <count group_id="O2" value="1952"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="466"/>
                    <measurement group_id="O2" value="495"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Specific IgE</title>
        <description>Number of participants with specific IgE (Phadiatop Infant) above the clinical cut-of level of 0.35.</description>
        <time_frame>13 months of age</time_frame>
        <population>This analysis includes children who participated with blood samples for this sub-study regarding specific IgE.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SSI strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Specific IgE</title>
          <description>Number of participants with specific IgE (Phadiatop Infant) above the clinical cut-of level of 0.35.</description>
          <population>This analysis includes children who participated with blood samples for this sub-study regarding specific IgE.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="743"/>
                <count group_id="O2" value="627"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55"/>
                    <measurement group_id="O2" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Standardized Weight at 13 Months</title>
        <description>To test that infants who get the BCG vaccine at birth respond in weight.The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.</description>
        <time_frame>13 months of age</time_frame>
        <population>This analysis only includes children with available follow-up data from telephone interviews or clinical examinations. As opposed to the primary outcome, follow-up was lower than 100%.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SS! strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Standardized Weight at 13 Months</title>
          <description>To test that infants who get the BCG vaccine at birth respond in weight.The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.</description>
          <population>This analysis only includes children with available follow-up data from telephone interviews or clinical examinations. As opposed to the primary outcome, follow-up was lower than 100%.</population>
          <units>Weight z-score at 13 months</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2052"/>
                <count group_id="O2" value="1950"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.58" spread="0.90"/>
                    <measurement group_id="O2" value="0.61" spread="0.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Psychomotor Development in Premature Infants</title>
        <description>To test that premature infants with gestational age less than 37 weeks who get the BCG vaccine at birth have unaffected psychomotor development measures: ASQ: Ages and stages questionnaire - a parent reported questionnaire that measures child psychomotor development. Total range of ASQ score: 0 to 300 points. Higher scores indicate higher level of psychomotor development.</description>
        <time_frame>13 months of age</time_frame>
        <population>This analysis only includes children from a particular subgroup (premature children, N = 144), who had with available follow-up data. As opposed to the primary outcome, follow-up was lower than 100%.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SS! strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Psychomotor Development in Premature Infants</title>
          <description>To test that premature infants with gestational age less than 37 weeks who get the BCG vaccine at birth have unaffected psychomotor development measures: ASQ: Ages and stages questionnaire - a parent reported questionnaire that measures child psychomotor development. Total range of ASQ score: 0 to 300 points. Higher scores indicate higher level of psychomotor development.</description>
          <population>This analysis only includes children from a particular subgroup (premature children, N = 144), who had with available follow-up data. As opposed to the primary outcome, follow-up was lower than 100%.</population>
          <units>Score on ASQ scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="59"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="141.8" spread="53"/>
                    <measurement group_id="O2" value="153.5" spread="53.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>DTaP-IPV-Hib Vaccination Coverage at 12 Months of Age</title>
        <description>To test that infants who get the BCG vaccine at birth has unaffected coverage with the subsequent 3rd diphtheria, tetanus, acellular pertussis, polio, Haemophilus influenzae type b (DTaP-IPV-Hib) vaccination scheduled to 12 months of age according to the Danish child vaccination programme. Since we did not expect all children to get their immunizations exactly at 12 months of age, the children were followed up until 13-months of age.</description>
        <time_frame>13 months of age</time_frame>
        <population>Per-protocol analysis excluding 11 children randomised to BCG who did not receive the vaccine, and 36 children randomised to control who received the BCG vaccine.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SSI strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>DTaP-IPV-Hib Vaccination Coverage at 12 Months of Age</title>
          <description>To test that infants who get the BCG vaccine at birth has unaffected coverage with the subsequent 3rd diphtheria, tetanus, acellular pertussis, polio, Haemophilus influenzae type b (DTaP-IPV-Hib) vaccination scheduled to 12 months of age according to the Danish child vaccination programme. Since we did not expect all children to get their immunizations exactly at 12 months of age, the children were followed up until 13-months of age.</description>
          <population>Per-protocol analysis excluding 11 children randomised to BCG who did not receive the vaccine, and 36 children randomised to control who received the BCG vaccine.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2018"/>
                <count group_id="O2" value="2097"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1175"/>
                    <measurement group_id="O2" value="1207"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Standardized Weight, Length and Head Circumference of Premature Children at 13 Months</title>
        <description>The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.</description>
        <time_frame>13 months of age</time_frame>
        <population>Premature children born with gestational age 32-36 weeks. This analysis only includes children from a particular subgroup (premature children, N = 144), who had with available follow-up data. As opposed to the primary outcome, follow-up was lower than 100%.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SSI strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Standardized Weight, Length and Head Circumference of Premature Children at 13 Months</title>
          <description>The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.</description>
          <population>Premature children born with gestational age 32-36 weeks. This analysis only includes children from a particular subgroup (premature children, N = 144), who had with available follow-up data. As opposed to the primary outcome, follow-up was lower than 100%.</population>
          <units>z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="63"/>
                <count group_id="O2" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Weight</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.33" spread="0.95"/>
                    <measurement group_id="O2" value="0.34" spread="1.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Length</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.10" spread="0.97"/>
                    <measurement group_id="O2" value="0.02" spread="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Head circumference</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.51" spread="0.97"/>
                    <measurement group_id="O2" value="0.57" spread="0.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Episodic Viral Wheeze</title>
        <description>Number of participants diagnosed with episodic viral wheeze by a physician and treated with anti-asthmatic medicine according to the telephone interview.</description>
        <time_frame>13 months</time_frame>
        <population>This analysis only includes children with available follow-up telephone interview data. As opposed to the primary outcome, follow-up was lower than 100%.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SS! strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Episodic Viral Wheeze</title>
          <description>Number of participants diagnosed with episodic viral wheeze by a physician and treated with anti-asthmatic medicine according to the telephone interview.</description>
          <population>This analysis only includes children with available follow-up telephone interview data. As opposed to the primary outcome, follow-up was lower than 100%.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2108"/>
                <count group_id="O2" value="2081"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="211"/>
                    <measurement group_id="O2" value="195"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Food Allergy</title>
        <description>Number of participants with food allergy diagnosed by a physician and mentioned in the telephone interview at 13 months of age</description>
        <time_frame>13 months</time_frame>
        <population>This analysis only includes children with available follow-up telephone interview data. As opposed to the primary outcome, follow-up was lower than 100%.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SSI strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Food Allergy</title>
          <description>Number of participants with food allergy diagnosed by a physician and mentioned in the telephone interview at 13 months of age</description>
          <population>This analysis only includes children with available follow-up telephone interview data. As opposed to the primary outcome, follow-up was lower than 100%.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2107"/>
                <count group_id="O2" value="2076"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Length at 13 Months of Age</title>
        <description>To test if infants who get the BCG vaccine at birth respond in length. The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.</description>
        <time_frame>13months</time_frame>
        <population>This analysis only includes children with available follow-up data. As opposed to the primary outcome, follow-up for this outcome was lower than 100%.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SS! strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Length at 13 Months of Age</title>
          <description>To test if infants who get the BCG vaccine at birth respond in length. The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.</description>
          <population>This analysis only includes children with available follow-up data. As opposed to the primary outcome, follow-up for this outcome was lower than 100%.</population>
          <units>Length z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2050"/>
                <count group_id="O2" value="1947"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.54" spread="0.99"/>
                    <measurement group_id="O2" value="0.55" spread="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Standardized Head Circumference at 13 Months of Age</title>
        <description>To test if infants who get the BCG vaccine at birth respond in head circumference. The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.</description>
        <time_frame>13 months</time_frame>
        <population>This analysis only includes children with available follow-up data. As opposed to the primary outcome, follow-up for this outcome was lower than 100%.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SS! strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Standardized Head Circumference at 13 Months of Age</title>
          <description>To test if infants who get the BCG vaccine at birth respond in head circumference. The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.</description>
          <population>This analysis only includes children with available follow-up data. As opposed to the primary outcome, follow-up for this outcome was lower than 100%.</population>
          <units>Head circumference z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2052"/>
                <count group_id="O2" value="1952"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.78" spread="0.93"/>
                    <measurement group_id="O2" value="0.76" spread="0.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Thymic Gland Size at 3 Months of Age</title>
        <description>To test that infants who receive the BCG at birth respond in thymic gland size defined by ultra sound examination. First, the thymus gland was identified in a horizontal scanning plane and the largest transverse diameter of the thymus was obtained. Second, in a sagittal scanning plane, the area of the largest lobe was assessed. Both measurements were obtained twice, and in case of more than 15% difference, both measurements were repeated. The mean of the two measurements were multiplied and defined as the thymic index.</description>
        <time_frame>3 months of age</time_frame>
        <population>This outcome was a sub-study to The Danish Calmette Study with 301 (BCG 153, Control 148) participating children.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SSI strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Thymic Gland Size at 3 Months of Age</title>
          <description>To test that infants who receive the BCG at birth respond in thymic gland size defined by ultra sound examination. First, the thymus gland was identified in a horizontal scanning plane and the largest transverse diameter of the thymus was obtained. Second, in a sagittal scanning plane, the area of the largest lobe was assessed. Both measurements were obtained twice, and in case of more than 15% difference, both measurements were repeated. The mean of the two measurements were multiplied and defined as the thymic index.</description>
          <population>This outcome was a sub-study to The Danish Calmette Study with 301 (BCG 153, Control 148) participating children.</population>
          <units>Thymic index</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="153"/>
                <count group_id="O2" value="148"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.10" lower_limit="31.22" upper_limit="34.81"/>
                    <measurement group_id="O2" value="34.24" lower_limit="32.42" upper_limit="36.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Leucocyte Count 4 Days After Randomisation/Vaccination</title>
        <description>To test if infants who receive the BCG at birth respond in leucocyte count (white blood cell count) measured as geometric mean (GM) cell concentrations (GM*10^9 cells/L).</description>
        <time_frame>4 days after randomisation/vaccination within 7 days after birth</time_frame>
        <population>This was a sub study among 153 children with blood-samples at 4 days after randomisation/vaccination.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SSI strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Leucocyte Count 4 Days After Randomisation/Vaccination</title>
          <description>To test if infants who receive the BCG at birth respond in leucocyte count (white blood cell count) measured as geometric mean (GM) cell concentrations (GM*10^9 cells/L).</description>
          <population>This was a sub study among 153 children with blood-samples at 4 days after randomisation/vaccination.</population>
          <units>cell concentrations (GM*10^9 cells/L)</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="75"/>
                <count group_id="O2" value="78"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.59" lower_limit="10.06" upper_limit="11.15"/>
                    <measurement group_id="O2" value="10.70" lower_limit="10.24" upper_limit="11.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Monocyte Count 4 Days After Randomisation/Vaccination</title>
        <description>To test if infants who receive the BCG at birth respond in monocyte count measured as geometric mean (GM) cell concentrations (GM*10^9 cells/L).</description>
        <time_frame>4 days after randomisation/vaccination within 7 days after birth</time_frame>
        <population>This was a sub study among 153 children with blood-samples at 4 days after randomisation/vaccination.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SSI strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Monocyte Count 4 Days After Randomisation/Vaccination</title>
          <description>To test if infants who receive the BCG at birth respond in monocyte count measured as geometric mean (GM) cell concentrations (GM*10^9 cells/L).</description>
          <population>This was a sub study among 153 children with blood-samples at 4 days after randomisation/vaccination.</population>
          <units>Cell concentrations (GM*10^9 cells/L)</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="75"/>
                <count group_id="O2" value="78"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.58" lower_limit="1.47" upper_limit="1.70"/>
                    <measurement group_id="O2" value="1.71" lower_limit="1.60" upper_limit="1.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Interferon Gamma Response</title>
        <description>To test that infants who receive the BCG at birth respond in interferon-gamma response upon stimulation with BCG. The interferon gamma response was defined as a value above the cut-off value of 107 pg/ml.</description>
        <time_frame>13 months of age</time_frame>
        <population>This is a sub study using bloodsamples. Only a small sub population from the overall trial participated.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SSI strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Interferon Gamma Response</title>
          <description>To test that infants who receive the BCG at birth respond in interferon-gamma response upon stimulation with BCG. The interferon gamma response was defined as a value above the cut-off value of 107 pg/ml.</description>
          <population>This is a sub study using bloodsamples. Only a small sub population from the overall trial participated.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="75"/>
                <count group_id="O2" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Antibody Concentration (AC) Against Tetanus of &gt; 0.1 IU/mL</title>
        <description>To test the tetenus antibody response in BCG-vaccinated vs. non-BCG vaccinated children following routine immunisation against tetanus at 3, 5 and 12 months of age in blood samples obtained 13 months of age.</description>
        <time_frame>13 months of age</time_frame>
        <population>This outcome was a sub-study with 158 participants. Antibody concentration (AC) of &gt; 0.1 IU/mL was considered protective</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SSI strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Antibody Concentration (AC) Against Tetanus of &gt; 0.1 IU/mL</title>
          <description>To test the tetenus antibody response in BCG-vaccinated vs. non-BCG vaccinated children following routine immunisation against tetanus at 3, 5 and 12 months of age in blood samples obtained 13 months of age.</description>
          <population>This outcome was a sub-study with 158 participants. Antibody concentration (AC) of &gt; 0.1 IU/mL was considered protective</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="78"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80"/>
                    <measurement group_id="O2" value="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Events of Common Cold</title>
        <description>To test that Danish infants who get the BCG vaccine at birth experience less events of common cold until 13 months of age than non-BCG-immunised infants.</description>
        <time_frame>13 months of age</time_frame>
        <population>This analysis only includes children with available follow-up data. As opposed to the primary outcome, follow-up for this outcome was lower than 100%.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SS! strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Events of Common Cold</title>
          <description>To test that Danish infants who get the BCG vaccine at birth experience less events of common cold until 13 months of age than non-BCG-immunised infants.</description>
          <population>This analysis only includes children with available follow-up data. As opposed to the primary outcome, follow-up for this outcome was lower than 100%.</population>
          <units>Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2096"/>
                <count group_id="O2" value="2071"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3990"/>
                    <measurement group_id="O2" value="3928"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Events of Pneumonia</title>
        <description>To test that Danish infants who get the BCG vaccine at birth get less pneumonia at 13 months of age than non-BCG-immunised infants.</description>
        <time_frame>13 months of age</time_frame>
        <population>This analysis only includes children with available follow-up data. As opposed to the primary outcome, follow-up for this outcome was lower than 100%.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SSI strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Events of Pneumonia</title>
          <description>To test that Danish infants who get the BCG vaccine at birth get less pneumonia at 13 months of age than non-BCG-immunised infants.</description>
          <population>This analysis only includes children with available follow-up data. As opposed to the primary outcome, follow-up for this outcome was lower than 100%.</population>
          <units>Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2100"/>
                <count group_id="O2" value="2070"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="207"/>
                    <measurement group_id="O2" value="162"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Events of Febrile Episodes</title>
        <description>To test that Danish infants who get the BCG vaccine at birth get less febrile episodes at 13 months of age than non-BCG-immunised infants.</description>
        <time_frame>13 months of age</time_frame>
        <population>This analysis only includes children with available follow-up data. As opposed to the primary outcome, follow-up for this outcome was lower than 100%.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SSI strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Events of Febrile Episodes</title>
          <description>To test that Danish infants who get the BCG vaccine at birth get less febrile episodes at 13 months of age than non-BCG-immunised infants.</description>
          <population>This analysis only includes children with available follow-up data. As opposed to the primary outcome, follow-up for this outcome was lower than 100%.</population>
          <units>Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2098"/>
                <count group_id="O2" value="2069"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1385"/>
                    <measurement group_id="O2" value="1302"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Events With Diarrhoea and Vomiting</title>
        <description>To test that Danish infants who get the BCG vaccine at birth develop less episodes with diarrhoea and vomiting at 13 months of age than non-BCG-immunised infants.</description>
        <time_frame>13 months of age</time_frame>
        <population>This analysis only includes children with available follow-up data. As opposed to the primary outcome, follow-up for this outcome was lower than 100%.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SS! strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Events With Diarrhoea and Vomiting</title>
          <description>To test that Danish infants who get the BCG vaccine at birth develop less episodes with diarrhoea and vomiting at 13 months of age than non-BCG-immunised infants.</description>
          <population>This analysis only includes children with available follow-up data. As opposed to the primary outcome, follow-up for this outcome was lower than 100%.</population>
          <units>Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2103"/>
                <count group_id="O2" value="2071"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="870"/>
                    <measurement group_id="O2" value="845"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Events of Acute Otitis Media</title>
        <description>To test that Danish infants who get the BCG vaccine at birth develop less acute otitis media at 13 months of age than non-BCG-immunised infants.</description>
        <time_frame>13 months of age</time_frame>
        <population>This analysis only includes children with available follow-up data. As opposed to the primary outcome, follow-up for this outcome was lower than 100%.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SSI strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Events of Acute Otitis Media</title>
          <description>To test that Danish infants who get the BCG vaccine at birth develop less acute otitis media at 13 months of age than non-BCG-immunised infants.</description>
          <population>This analysis only includes children with available follow-up data. As opposed to the primary outcome, follow-up for this outcome was lower than 100%.</population>
          <units>Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2098"/>
                <count group_id="O2" value="2072"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="595"/>
                    <measurement group_id="O2" value="591"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Events of Febrile Convulsions</title>
        <description>To test that Danish infants who get the BCG vaccine at birth develop less febrile convulsions at 13 months of age than non-BCG-immunised infants.</description>
        <time_frame>13 months of age</time_frame>
        <population>This analysis only includes children with available follow-up data. As opposed to the primary outcome, follow-up for this outcome was lower than 100%.</population>
        <group_list>
          <group group_id="O1">
            <title>BCG-vaccine</title>
            <description>SSI strain 1331 standard dose</description>
          </group>
          <group group_id="O2">
            <title>Control Children</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Events of Febrile Convulsions</title>
          <description>To test that Danish infants who get the BCG vaccine at birth develop less febrile convulsions at 13 months of age than non-BCG-immunised infants.</description>
          <population>This analysis only includes children with available follow-up data. As opposed to the primary outcome, follow-up for this outcome was lower than 100%.</population>
          <units>Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2103"/>
                <count group_id="O2" value="2070"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44"/>
                    <measurement group_id="O2" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Decisional Conflict Scale Score</title>
        <description>After parents having made the decision about whether to accept vaccination of their newborn through participation in The Danish Calmette Study, O'Connor's Decisional Conflict Scale was used to identify decisional conflicts. The score ranges from 0 (no decisional conflict) til 100 (maximum decisional conflict). Scores lower than 25 are associated with implementing decisions; scores exceeding 37.5 are associated with decision delay or feeling unsure about implementation; so a low score reflects a low level of doubt about the decision about participation/decline participation in the trial, and a high score reflects a high level of doubt.</description>
        <time_frame>The decisional conflict score was measured before randomisation</time_frame>
        <population>This outcome was a sub-study to The Danish Calmette Study with 667 participating mothers and 320 declining mothers.</population>
        <group_list>
          <group group_id="O1">
            <title>Participating Mothers</title>
            <description>Mothers who decided to let their child participate in the study</description>
          </group>
          <group group_id="O2">
            <title>Declining Mothers</title>
            <description>Mothers who decided not to let their child participate in the study</description>
          </group>
        </group_list>
        <measure>
          <title>Decisional Conflict Scale Score</title>
          <description>After parents having made the decision about whether to accept vaccination of their newborn through participation in The Danish Calmette Study, O'Connor's Decisional Conflict Scale was used to identify decisional conflicts. The score ranges from 0 (no decisional conflict) til 100 (maximum decisional conflict). Scores lower than 25 are associated with implementing decisions; scores exceeding 37.5 are associated with decision delay or feeling unsure about implementation; so a low score reflects a low level of doubt about the decision about participation/decline participation in the trial, and a high score reflects a high level of doubt.</description>
          <population>This outcome was a sub-study to The Danish Calmette Study with 667 participating mothers and 320 declining mothers.</population>
          <units>decisional conflict score</units>
          <param>Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="667"/>
                <count group_id="O2" value="320"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.8" lower_limit="0" upper_limit="53.1"/>
                    <measurement group_id="O2" value="17.2" lower_limit="0" upper_limit="67.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <method_desc>Mann-Whitney-test comparing the decisional conflict scores of participating mothers vs. declining mothers.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Quality of Communication and Information</title>
        <description>To test that the use of telephone and internet was acceptable in the study population using the Quality of Informed Consent (QuIC) questionnaire. The questionnaire was divided into six categories; five on study comprehension and one on satisfaction with the information process. The items in the first five categories could be answered with &quot;yes&quot;, &quot;no&quot; or &quot;do not know&quot;. The last category was rated on a 7-point Likert scale, with 1 being &quot;very dissatisfied&quot; and 7 being &quot;very satisfied&quot;. The primary outcome was the sum of the score for comprehension items and satisfaction items. Comprehension items were scored 1 point for each correct answer and 0 points for each incorrect answer. Satisfaction items were scored as rated on the 7-point Likert scale. Total score ranged from 7 to 69 points, comprehension score from 0 to 20 points and satisfaction score from 7 to 49 points. The higher score, the better comprehension and satisfaction.</description>
        <time_frame>2 days after the information was given</time_frame>
        <population>This is a small, separate sub-study. 59 + 59 participants had sufficient follow-up data to participate in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Telephone</title>
            <description>Randomized to receive information about the study by telephone</description>
          </group>
          <group group_id="O2">
            <title>Face-to-face</title>
            <description>Randomized to receive information about the study by standard face-to-face consultation.</description>
          </group>
        </group_list>
        <measure>
          <title>Quality of Communication and Information</title>
          <description>To test that the use of telephone and internet was acceptable in the study population using the Quality of Informed Consent (QuIC) questionnaire. The questionnaire was divided into six categories; five on study comprehension and one on satisfaction with the information process. The items in the first five categories could be answered with &quot;yes&quot;, &quot;no&quot; or &quot;do not know&quot;. The last category was rated on a 7-point Likert scale, with 1 being &quot;very dissatisfied&quot; and 7 being &quot;very satisfied&quot;. The primary outcome was the sum of the score for comprehension items and satisfaction items. Comprehension items were scored 1 point for each correct answer and 0 points for each incorrect answer. Satisfaction items were scored as rated on the 7-point Likert scale. Total score ranged from 7 to 69 points, comprehension score from 0 to 20 points and satisfaction score from 7 to 49 points. The higher score, the better comprehension and satisfaction.</description>
          <population>This is a small, separate sub-study. 59 + 59 participants had sufficient follow-up data to participate in the analysis.</population>
          <units>Score on QuIC scale</units>
          <param>Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="59"/>
                <count group_id="O2" value="59"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.40" lower_limit="58" upper_limit="65"/>
                    <measurement group_id="O2" value="64.42" lower_limit="63" upper_limit="67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>BCG-vaccine</title>
        </group>
        <group group_id="E2">
          <title>Control Children (no Intervention)</title>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="65" subjects_at_risk="2129"/>
                <counts group_id="E2" subjects_affected="45" subjects_at_risk="2133"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Dead</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="2129"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2133"/>
              </event>
              <event>
                <sub_title>Other than dead</sub_title>
                <description>Registered as: life-threatening events, hospitalizations, events causing disability. No life-threatening events, or events causing disability were however registered.</description>
                <counts group_id="E1" events="62" subjects_affected="62" subjects_at_risk="2129"/>
                <counts group_id="E2" events="44" subjects_affected="44" subjects_at_risk="2133"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="233" subjects_at_risk="2129"/>
                <counts group_id="E2" subjects_affected="123" subjects_at_risk="2133"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Other than BCG-vaccine related</sub_title>
                <counts group_id="E1" events="2129" subjects_affected="21" subjects_at_risk="2129"/>
                <counts group_id="E2" events="2133" subjects_affected="123" subjects_at_risk="2133"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>BCG-vaccine related event</sub_title>
                <counts group_id="E1" events="212" subjects_affected="212" subjects_at_risk="2129"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2133"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The allocation was planned to be stratified by sex, study site, and prematurity, however, due to a programming error the allocation was stratified only by prematurity.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Lone Graff Stensballe, Research leader, Pediatrician, PhD</name_or_title>
      <organization>Rigshospitalet</organization>
      <phone>+0045 35459727</phone>
      <email>lone.graff.stensballe@regionh.dk</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01694108
org study id: EudraCT2010-021979-85
nct id: NCT01694108
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
In high-income societies the use of health care and medication is steadily increasing.
      Children have high morbidity, many visits at the general practitioner, an increasing number
      of hospitalisations, and an increasing use of medication. And, when children are ill, someone
      has to stay home to care for them. An un-explained global increase in the incidence of the
      allergic diseases eczema, wheezing, asthma and allergies means that 25% of high-income
      populations are affected. Cheap preventive measures are highly warranted. Recent studies have
      shown a positive, non-specific effect of early Bacille Calmette Guérin (BCG) immunisation on
      neonatal mortality in low-income countries and suggested a positive, non-specific effect on
      allergic disease in high-income countries. "Non-specific" means that the vaccine effect goes
      beyond prevention of the targeted disease, i.e. the BCG vaccine benefits the health status of
      the immunised individual in ways unrelated to protection against tuberculosis (TB). For
      instance, in a recent randomised trial in West Africa the investigators showed that the BCG
      vaccine at birth was safe in low birth weight (LBW) infants and significantly reduced
      neonatal mortality in these children, with a significant long-lasting effect on infant
      mortality in the smallest newborns with a birth weight <1.5 kg. There is an urgent need to
      explore the huge potential of the BCG's beneficial immune-stimulatory effects among children
      in high-income populations.

      Therefore, the investigators will carry out a large prospective randomised clinical trial in
      Denmark primarily designed to test the hypothesis that infants who get the BCG vaccine at
      birth experience 20% fewer hospitalisations during early childhood.

      Secondary outcomes

        1. To test the hypothesis that infants who get the BCG vaccine at birth are prescribed less
           antibiotics during early childhood than non-BCG-immunised infants.

        2. To test the hypothesis that Danish infants who get the BCG vaccine at birth develop less
           eczema, asthmatic bronchitis/wheeze and food allergy at 3 and 12 months of age:
           self-reported, diagnosed by a physician, or found at clinical examination; and are
           prescribed less anti-eczema/asthma/allergy medication during early childhood than
           non-BCG-immunised infants.

        3. To test the hypothesis that infants who receive the BCG at birth respond in paraclinical
           measures: Specific IgE, thymic gland size, leucocyte count and differentiation, monocyte
           memory, cytokine profiles, and antibody titres following immunisation against
           diphtheria, tetanus, pertussis, pneumococcus, hemophilus.

        4. To test the hypothesis that infants who get the BCG vaccine at birth respond in growth
           measures: weight, length and head circumference.

        5. To test the hypothesis that infants who get the BCG vaccine at birth respond with
           decreased morbidity: common cold, pneumonia, febrile episodes, diarrhoea and vomiting,
           acute otitis media, febrile convulsions.

        6. To test the hypothesis that premature infants with gestational age less than 37 weeks
           who get the BCG vaccine at birth have unaffected psychomotor development measures: Ages
           and Stages scores.

        7. To test the hypothesis that infants who get the BCG vaccine at birth has unaffected
           coverage with the subsequent vaccinations in the Child Vaccination Programme.

        8. To test the above mentioned hypotheses specifically in the strata of premature and
           low-birth-weight Danish infants.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Prevention
masking: Single (Outcomes Assessor)
measure: All-cause Hospitalisations
time frame: 0-15 months of age
description: To test that infants who get the BCG vaccine at birth experience 20% fewer hospitalisations in early childhood than non-BCG-immunised infants.
measure: Antibiotics
time frame: 0-15 months of age
description: To test that infants who get the BCG vaccine at birth are prescribed less antibiotics during early childhood than non-BCG-immunised infants. Use of antibiotics was defined as one or more precriptions of systemic antibiotics (ATC groups J01, J02, J05, all subgroups inclusive).
measure: Atopic Dermatitis
time frame: 13 months of age
description: To test if BCG vaccination within 7 days after birth influence the risk of atopic dermatitis defined by clinical examination at 13 months of age using "scoring atopic dermatitis (SCORAD)" or by parental report of physician diagnosed atopic dermatitis in the telephone interview at 13 months of age.
measure: Specific IgE
time frame: 13 months of age
description: Number of participants with specific IgE (Phadiatop Infant) above the clinical cut-of level of 0.35.
measure: Standardized Weight at 13 Months
time frame: 13 months of age
description: To test that infants who get the BCG vaccine at birth respond in weight.The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.
measure: Psychomotor Development in Premature Infants
time frame: 13 months of age
description: To test that premature infants with gestational age less than 37 weeks who get the BCG vaccine at birth have unaffected psychomotor development measures: ASQ: Ages and stages questionnaire - a parent reported questionnaire that measures child psychomotor development. Total range of ASQ score: 0 to 300 points. Higher scores indicate higher level of psychomotor development.
measure: DTaP-IPV-Hib Vaccination Coverage at 12 Months of Age
time frame: 13 months of age
description: To test that infants who get the BCG vaccine at birth has unaffected coverage with the subsequent 3rd diphtheria, tetanus, acellular pertussis, polio, Haemophilus influenzae type b (DTaP-IPV-Hib) vaccination scheduled to 12 months of age according to the Danish child vaccination programme. Since we did not expect all children to get their immunizations exactly at 12 months of age, the children were followed up until 13-months of age.
measure: Standardized Weight, Length and Head Circumference of Premature Children at 13 Months
time frame: 13 months of age
description: The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.
measure: Episodic Viral Wheeze
time frame: 13 months
description: Number of participants diagnosed with episodic viral wheeze by a physician and treated with anti-asthmatic medicine according to the telephone interview.
measure: Food Allergy
time frame: 13 months
description: Number of participants with food allergy diagnosed by a physician and mentioned in the telephone interview at 13 months of age
measure: Length at 13 Months of Age
time frame: 13months
description: To test if infants who get the BCG vaccine at birth respond in length. The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.
measure: Standardized Head Circumference at 13 Months of Age
time frame: 13 months
description: To test if infants who get the BCG vaccine at birth respond in head circumference. The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.
measure: Thymic Gland Size at 3 Months of Age
time frame: 3 months of age
description: To test that infants who receive the BCG at birth respond in thymic gland size defined by ultra sound examination. First, the thymus gland was identified in a horizontal scanning plane and the largest transverse diameter of the thymus was obtained. Second, in a sagittal scanning plane, the area of the largest lobe was assessed. Both measurements were obtained twice, and in case of more than 15% difference, both measurements were repeated. The mean of the two measurements were multiplied and defined as the thymic index.
measure: Leucocyte Count 4 Days After Randomisation/Vaccination
time frame: 4 days after randomisation/vaccination within 7 days after birth
description: To test if infants who receive the BCG at birth respond in leucocyte count (white blood cell count) measured as geometric mean (GM) cell concentrations (GM*10^9 cells/L).
measure: Monocyte Count 4 Days After Randomisation/Vaccination
time frame: 4 days after randomisation/vaccination within 7 days after birth
description: To test if infants who receive the BCG at birth respond in monocyte count measured as geometric mean (GM) cell concentrations (GM*10^9 cells/L).
measure: Interferon Gamma Response
time frame: 13 months of age
description: To test that infants who receive the BCG at birth respond in interferon-gamma response upon stimulation with BCG. The interferon gamma response was defined as a value above the cut-off value of 107 pg/ml.
measure: Number of Participants With Antibody Concentration (AC) Against Tetanus of > 0.1 IU/mL
time frame: 13 months of age
description: To test the tetenus antibody response in BCG-vaccinated vs. non-BCG vaccinated children following routine immunisation against tetanus at 3, 5 and 12 months of age in blood samples obtained 13 months of age.
measure: Number of Events of Common Cold
time frame: 13 months of age
description: To test that Danish infants who get the BCG vaccine at birth experience less events of common cold until 13 months of age than non-BCG-immunised infants.
measure: Number of Events of Pneumonia
time frame: 13 months of age
description: To test that Danish infants who get the BCG vaccine at birth get less pneumonia at 13 months of age than non-BCG-immunised infants.
measure: Number of Events of Febrile Episodes
time frame: 13 months of age
description: To test that Danish infants who get the BCG vaccine at birth get less febrile episodes at 13 months of age than non-BCG-immunised infants.
measure: Number of Events With Diarrhoea and Vomiting
time frame: 13 months of age
description: To test that Danish infants who get the BCG vaccine at birth develop less episodes with diarrhoea and vomiting at 13 months of age than non-BCG-immunised infants.
measure: Number of Events of Acute Otitis Media
time frame: 13 months of age
description: To test that Danish infants who get the BCG vaccine at birth develop less acute otitis media at 13 months of age than non-BCG-immunised infants.
measure: Number of Events of Febrile Convulsions
time frame: 13 months of age
description: To test that Danish infants who get the BCG vaccine at birth develop less febrile convulsions at 13 months of age than non-BCG-immunised infants.
measure: Decisional Conflict Scale Score
time frame: The decisional conflict score was measured before randomisation
description: After parents having made the decision about whether to accept vaccination of their newborn through participation in The Danish Calmette Study, O'Connor's Decisional Conflict Scale was used to identify decisional conflicts. The score ranges from 0 (no decisional conflict) til 100 (maximum decisional conflict). Scores lower than 25 are associated with implementing decisions; scores exceeding 37.5 are associated with decision delay or feeling unsure about implementation; so a low score reflects a low level of doubt about the decision about participation/decline participation in the trial, and a high score reflects a high level of doubt.
measure: Quality of Communication and Information
time frame: 2 days after the information was given
description: To test that the use of telephone and internet was acceptable in the study population using the Quality of Informed Consent (QuIC) questionnaire. The questionnaire was divided into six categories; five on study comprehension and one on satisfaction with the information process. The items in the first five categories could be answered with "yes", "no" or "do not know". The last category was rated on a 7-point Likert scale, with 1 being "very dissatisfied" and 7 being "very satisfied". The primary outcome was the sum of the score for comprehension items and satisfaction items. Comprehension items were scored 1 point for each correct answer and 0 points for each incorrect answer. Satisfaction items were scored as rated on the 7-point Likert scale. Total score ranged from 7 to 69 points, comprehension score from 0 to 20 points and satisfaction score from 7 to 49 points. The higher score, the better comprehension and satisfaction.
arm group label: BCG-vaccine (SSI)
arm group type: Experimental
description: Children born to mothers, who have accepted to participate, will be randomised to either intervention group or to the control group at birth. Block-randomisation stratified by hospital, gender and gestational age (≥37 weeks of gestation vs. < 37 weeks of gestation) will be performed electronically just before vaccination by the overall study electronic case report system (e-crf).
Children randomised to the BCG vaccination group will receive an intradermal BCG vaccine (Statens Serum Institute "CG vaccine" in the standard dose 0.05 ml in the upper, lateral part of the arm of the child by a specially trained midwife or a study physician.
arm group label: No Intervention
arm group type: No Intervention
description: Control children will be treated as usual, since no suitable placebo exists.
intervention type: Biological
intervention name: BCG-vaccine (SSI)
arm group label: BCG-vaccine (SSI)
criteria: 
gender: All
minimum age: N/A
maximum age: 7 Days
healthy volunteers: No
last name: Lone G Stensballe, MD, PhD
role: Principal Investigator
affiliation: Rigshospitalet. The Danish National Hospital in Denmark.
facility: 
facility: 
facility: 
country: Denmark
url: http://Calmette-studiet.dk
description: Study home page
responsible party type: Sponsor-Investigator
investigator affiliation: Rigshospitalet, Denmark
investigator full name: Lone Graff Stensballe
investigator title: MD, PhD
mesh term: BCG Vaccine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The allocation was planned to be stratified by sex, study site, and prematurity, however, due to a programming error the allocation was stratified only by prematurity.
point of contact: 