<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/NCT01702233</url>
  </required_header>
  <id_info>
    <org_study_id>TRARO</org_study_id>
    <secondary_id>2012-003393-12</secondary_id>
    <nct_id>NCT01702233</nct_id>
  </id_info>
  <brief_title>TRARO (Traumeel® S in Rotator Cuff Syndrome)-Study</brief_title>
  <acronym>TRARO</acronym>
  <official_title>Treatment of Rotator Cuff Syndrome and Bursitis: A Double Blind, Controlled Trial to Assess the Efficacy and Safety of Traumeel® S Injection Versus Corticosteroid Injections and Versus Placebo</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Biologische Heilmittel Heel GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Biologische Heilmittel Heel GmbH</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate functional, clinical, and subjective parameters in patients with rotator cuff&#xD;
      syndrome and bursitis treated with Traumeel® S injections versus corticosteroid injections&#xD;
      and versus placebo. 160 patients are planned to be randomised (i.e., 64 patients per active&#xD;
      treatment group and 32 patients in the placebo group) in 9 investigator sites in Germany,&#xD;
      Belgium and Spain.&#xD;
&#xD;
      Finally 176 patients have been randomized (73 Traumeel, 67 Fortecortin and 36 Placebo) and&#xD;
      175 of them received at least one dosage of treatment&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Duration of the study were 16 weeks. Duration of Treatments were 15 days, applying one&#xD;
      injection of 2 ml od study medication at days 1, 8, and 15. There was a follow up visit at&#xD;
      day 22 (Primary endpoint), a telephone visit at week 9 and a final visit at week 15.&#xD;
&#xD;
      Standard descriptive summary statistics were calculated for continuous variables (i.e.&#xD;
      arithmetic mean, standard deviation, minimum value, median, maximum value, number of&#xD;
      non-missing values). All statistical analyses in this study were of exploratory nature. The&#xD;
      summaries of the efficacy parameters, the statistical analyses of the primary efficacy&#xD;
      variable, and the statistical analyses of the secondary efficacy variables were performed on&#xD;
      the PP Set. These summaries and analyses were supported by corresponding summaries and&#xD;
      exploratory statistical analyses performed on the Full Analysis Set. Missing values for all&#xD;
      efficacy parameters were imputed by the last observation carried forward (LOCF) approach. The&#xD;
      Modified Per-Protocol (MPP) Set excluded from the PP Set also all patients having taken&#xD;
      unallowed concomitant medication after Visit 5 and was used as a secondary population for the&#xD;
      analysis of efficacy. All statistical tests were two-sided with a significance level of&#xD;
      (alpha) = 0.05, unless specified otherwise. The primary efficacy variable was the change from&#xD;
      baseline in VAS for abduction rotation pain at Visit 5 (Day 22) (Traumeel® S injections&#xD;
      versus corticoid injections) for active external rotation.&#xD;
&#xD;
      A one-sided test of non-inferiority of Traumeel® S with respect to dexamethasone at level&#xD;
      0.025 was computed using an analysis of covariance (ANCOVA) model with treatment group as&#xD;
      qualitative factor and the baseline value of the abduction rotation pain VAS for active&#xD;
      external rotation as a covariate. The test decision was based on a one-sided 97.5% confidence&#xD;
      interval for the corresponding treatment difference. The non-inferiority margin was set to 13&#xD;
      mm on a 0 - 100 mm VAS scale.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2013</start_date>
  <completion_date type="Actual">June 2014</completion_date>
  <primary_completion_date type="Actual">April 2014</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Abduction Rotation Pain VAS at Visit 5 (Day 22) (Traumeel® S Injections Versus Fortecortin) for Active External Rotation</measure>
    <time_frame>Baseline to Day 22</time_frame>
    <description>VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain). Change = (Day 22 score -- baseline score).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Abduction Rotation Pain VAS for Active External Rotation - Comparison With Placebo Visit 5 (Day 22)</measure>
    <time_frame>Baseline vs. Day 22</time_frame>
    <description>VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Abduction Rotation Pain VAS for Active External Rotation - Comparison With Placebo Visit 7 (Day 105)</measure>
    <time_frame>Baseline vs. Day 105</time_frame>
    <description>VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Abduction Rotation Pain VAS for Active External Rotation - Comparison With Fortecortin at Visit 7 (Day 105)</measure>
    <time_frame>Baseline vs. day 105</time_frame>
    <description>VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 5 (Day 22), Traumeel vs Placebo</measure>
    <time_frame>Baseline vs. Day 22</time_frame>
    <description>Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 7 (Day 105), Traumeel vs Placebo</measure>
    <time_frame>Baseline vs. day 105</time_frame>
    <description>Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 5 (Day 22) Traumeel vs Fortecortin</measure>
    <time_frame>Baseline vs. Day 22</time_frame>
    <description>Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 7 (Day 105), Traumeel vs Fortecortin</measure>
    <time_frame>Baseline vs. Day 105</time_frame>
    <description>Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Jobe Test at Visit 5 (Day 15) With Measurement of Pain</measure>
    <time_frame>Baseline vs. Day 22</time_frame>
    <description>This test looked for pain and weakness and was to be examined as active movement. Patients have to stand with shoulders in 90 degrees of abduction, 30 degrees of forward flexion and then internally rotating arm completely i.e., thumb pointing down. This was done to see if the patient was able to resist the clinician's attempts to depress the upper arm to look for muscle weakness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Jobe Test at Visit 5 (Day 22) With Measurement of Weakness</measure>
    <time_frame>Baseline vs. day 22</time_frame>
    <description>This test looked for pain and weakness and was to be examined as active movement. Patients have to stand with shoulders in 90 degrees of abduction, 30 degrees of forward flexion and then internally rotating arm completely i.e., thumb pointing down. This was done to see if the patient was able to resist the clinician's attempts to depress the upper arm to look for muscle weakness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Painful Arc Test at Visit 5 (Day 22)</measure>
    <time_frame>Baseline vs. day 22</time_frame>
    <description>The amount of pain that disappeared by further abduction in the range between 60° and 120° was to be measured, with measurement of pain being positive/negative. The idea behind the test is the subacromial space in abduction becomes smaller, whereby compression of the rotator cuff and the subacromial bursa occurs (impingement test).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in DASH at Visit 5 (Day 22)</measure>
    <time_frame>Baseline vs. Day 22</time_frame>
    <description>The score from the questions answered on the DASH (Disaability of the Arm, Shoulder and Hand) questionnaire were evaluated on both shoulders at screening and on the target shoulder at the later visits. Any changes between the score from baseline was used to evaluate efficacy.&#xD;
The score consists of a basic questionnaire of 30 questions regarding the daily activities with the answer options from &quot;no difficulty&quot; (value 1) to &quot;unable&quot; (value 5).&#xD;
The calculation is: ((sum of values of responses/number of responses)-1) X 25. Best possible result is 0, worst possible result is 100. The score may not be calculated if there are more than 3 missing answers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in DASH at Visit 7 (Day 105)</measure>
    <time_frame>Baseline vs. Day 105</time_frame>
    <description>The score from the questions answered on the DASH (Disaability of the Arm, Shoulder and Hand) questionnaire were evaluated on both shoulders at screening and on the The score consists of a basic questionnaire of 30 questions regarding the daily activities with the answer options from &quot;no difficulty&quot; (value 1) to &quot;unable&quot; (value 5).&#xD;
The calculation is: ((sum of values of responses/number of responses)-1) X 25. Best possible result is 0, worst possible result is 100. The score may not be calculated if there are more than 3 missing answers.target shoulder at the later visits. Any changes between the score from baseline was used to evaluate efficacy</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">175</enrollment>
  <condition>Rotator Cuff Syndrome</condition>
  <condition>Shoulder Bursitis</condition>
  <arm_group>
    <arm_group_label>Traumeel S inj.</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fortecortin/Dexamethasone 8 mg inj</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Fortecortin/Dexamethasone 8 mg/2 ml inj. subacromial 3 times at days 1, 8 and 15</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Saline inj.</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Saline inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Traumeel S inj</intervention_name>
    <description>Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
    <arm_group_label>Traumeel S inj.</arm_group_label>
    <other_name>Traumeel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fortecortin/Dexamethasone 8 mg/2 ml inj</intervention_name>
    <description>Fortecortin/Dexamethasone 8 mg/2 ml inj. subacromial 3 times at days 1, 8 and 15</description>
    <arm_group_label>Fortecortin/Dexamethasone 8 mg inj</arm_group_label>
    <other_name>Dexamethasone 8 mg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline inj</intervention_name>
    <description>Saline inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
    <arm_group_label>Saline inj.</arm_group_label>
    <other_name>Placebo inj</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female patients with acute episodes of chronic rotator cuff syndrome and/or&#xD;
             bursitis: tendinopathy of the supraspinatus tendon, bursitis, or partial degenerative&#xD;
             tears of the supraspinatus and/or infraspinatus tendon (differentiation by&#xD;
             ultrasonography)&#xD;
&#xD;
          2. Age 40 to 65 years, inclusive&#xD;
&#xD;
          3. Willing and able to understand and sign an approved informed consent form&#xD;
&#xD;
          4. Not pregnant (as proven by negative pregnancy test before first study drug&#xD;
             administration) or breast-feeding. Females of childbearing potential (including those&#xD;
             less than one year post-menopausal) must agree to maintain reliable birth control&#xD;
             throughout the study, i.e. an established use of oral, injected or implanted hormonal&#xD;
             contraception, female sterilization by hysterectomy, bilateral oophorectomy, or&#xD;
             bilateral tubal exeresis, intrauterine device ([IUD] or coil or barrier method (e.g.&#xD;
             diaphragm, cervical/vault cap) plus spermicidal cream/gel&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Calcifications in shoulder joint&#xD;
&#xD;
          2. Complete rotator cuff tears&#xD;
&#xD;
          3. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs). Previous treatment with&#xD;
             NSAIDs is allowed, with a wash-out period of 1 week; paracetamol can be taken until 48&#xD;
             hours before baseline visit&#xD;
&#xD;
          4. Corticoid therapy by mouth or by injection within the previous 3 months prior to&#xD;
             screening&#xD;
&#xD;
          5. Any contraindication for corticoid therapy&#xD;
&#xD;
          6. Physical Therapy, acupuncture, transcutaneous electrical nerve stimulation (TENS) and&#xD;
             shock-wave therapy (within 30 days prior to screening)&#xD;
&#xD;
          7. Treatment with anticoagulants (except low-dose aspirin)&#xD;
&#xD;
          8. Diabetic patients including borderline cases (glycosylated fraction of hemoglobin&#xD;
             [HbA1c] &gt; 7.0% at screening)&#xD;
&#xD;
          9. Clinically significant shoulder joint deformities&#xD;
&#xD;
         10. Major injury, including sports-related injury, to the shoulder within the past year&#xD;
&#xD;
         11. Significant osteoarthritis of the shoulder&#xD;
&#xD;
         12. Cervical spine disorder (that could confound the clinical assessment) that has been&#xD;
             symptomatic and required active treatment within the past three months before&#xD;
             screening&#xD;
&#xD;
         13. Any active musculoskeletal disease that could confound the diagnosis/evaluation of the&#xD;
             painful shoulder, any neurological aetiology of the pain, or any acute infection of&#xD;
             the shoulder joint&#xD;
&#xD;
         14. Any major surgery, arthroplasty, or arthroscopy in the signal shoulder within 6 months&#xD;
             of screening or planned surgery within the duration of the study&#xD;
&#xD;
         15. Prior history of any malignancy (with the exception of basal cell carcinoma) treated&#xD;
             less than 2 years ago&#xD;
&#xD;
         16. Patients with rheumatic polymyalgia&#xD;
&#xD;
         17. Known or suspected allergies against one or any particular ingredients of Traumeel® S&#xD;
             or of other study preparations&#xD;
&#xD;
         18. Presence of serious gastrointestinal, renal, hepatic, pulmonary, cardiovascular,&#xD;
             neurological disease or other known systemic disease (like leukemia, tuberculosis,&#xD;
             immune mediated diseases, multiple sclerosis, Acquired Immuno Deficiency Syndrome,&#xD;
             Human Immunodeficiency Virus-infections or other chronic virus-infections) that might&#xD;
             interfere with the outcome of the study or the patient's ability to comply with study&#xD;
             requirements.&#xD;
&#xD;
         19. Presence of infections and/or skin diseases in the area of the injection site&#xD;
             (including psoriasis)&#xD;
&#xD;
         20. Clinically significant abnormal laboratory values (as judged of the investigator) at&#xD;
             the screening visit&#xD;
&#xD;
         21. Consumption of any investigational product within one month prior to the screening&#xD;
             visit&#xD;
&#xD;
         22. Patients who are likely to be non-compliant or uncooperative during the study, as&#xD;
             judged by the investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Luc Vandenbossche, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Physical and Rehabilitation Medicine University Ghent, BE</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Luc Vandenbossche</name>
      <address>
        <city>Ghent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>January 2016</verification_date>
  <study_first_submitted>October 4, 2012</study_first_submitted>
  <study_first_submitted_qc>October 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2012</study_first_posted>
  <results_first_submitted>June 22, 2015</results_first_submitted>
  <results_first_submitted_qc>January 27, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">February 24, 2016</results_first_posted>
  <last_update_submitted>January 27, 2016</last_update_submitted>
  <last_update_submitted_qc>January 27, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 24, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bursitis</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Rotator Cuff Injuries</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Dexamethasone acetate</mesh_term>
    <mesh_term>BB 1101</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>176 patients have been randomized, 175 of them started treatment. 1 Patient in Treatment arm Traumeel S withdrew consent before first dose.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Traumeel S Inj.</title>
          <description>Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
        </group>
        <group group_id="P2">
          <title>Fortecortin/Dexamethasone 8 mg Inj</title>
          <description>Fortecortin/Dexamethasone 8 mg/2 ml inj. subacromial 3 times at days 1, 8 and 15</description>
        </group>
        <group group_id="P3">
          <title>Saline Inj.</title>
          <description>Saline inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="72"/>
                <participants group_id="P2" count="67"/>
                <participants group_id="P3" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Full Analysis Set (ITT)</title>
              <participants_list>
                <participants group_id="P1" count="66"/>
                <participants group_id="P2" count="63"/>
                <participants group_id="P3" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Per Protocol Set</title>
              <participants_list>
                <participants group_id="P1" count="58"/>
                <participants group_id="P2" count="58"/>
                <participants group_id="P3" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="66"/>
                <participants group_id="P2" count="64">One of these Patient completed the Trial but had no valid outcome measure after enrolment</participants>
                <participants group_id="P3" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Traumeel S Inj.</title>
          <description>Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
        </group>
        <group group_id="B2">
          <title>Fortecortin/Dexamethasone 8 mg Inj</title>
          <description>Fortecortin/Dexamethasone 8 mg/2 ml inj. subacromial 3 times at days 1, 8 and 15</description>
        </group>
        <group group_id="B3">
          <title>Saline Inj.</title>
          <description>Saline inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
        </group>
        <group group_id="B4">
          <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="72"/>
            <count group_id="B2" value="67"/>
            <count group_id="B3" value="36"/>
            <count group_id="B4" value="175"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="72"/>
                    <measurement group_id="B2" value="67"/>
                    <measurement group_id="B3" value="36"/>
                    <measurement group_id="B4" value="175"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51.00" spread="6.90"/>
                    <measurement group_id="B2" value="51.90" spread="7.02"/>
                    <measurement group_id="B3" value="51.80" spread="6.74"/>
                    <measurement group_id="B4" value="51.50" spread="6.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="77"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="20"/>
                    <measurement group_id="B4" value="98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="72"/>
                    <measurement group_id="B2" value="66"/>
                    <measurement group_id="B3" value="35"/>
                    <measurement group_id="B4" value="173"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Belgium</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Germany</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="52"/>
                    <measurement group_id="B2" value="51"/>
                    <measurement group_id="B3" value="25"/>
                    <measurement group_id="B4" value="128"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Screening Height</title>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="171.3" spread="10.24"/>
                    <measurement group_id="B2" value="170.6" spread="8.01"/>
                    <measurement group_id="B3" value="169.9" spread="11.32"/>
                    <measurement group_id="B4" value="170.8" spread="9.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Screening Weight</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="76.4" spread="16.57"/>
                    <measurement group_id="B2" value="79.2" spread="14.90"/>
                    <measurement group_id="B3" value="78.8" spread="16.90"/>
                    <measurement group_id="B4" value="78" spread="15.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25.92" spread="4.455"/>
                    <measurement group_id="B2" value="27.29" spread="5.455"/>
                    <measurement group_id="B3" value="27.14" spread="4.382"/>
                    <measurement group_id="B4" value="26.69" spread="4.866"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Abduction Rotation Pain VAS at Visit 5 (Day 22) (Traumeel® S Injections Versus Fortecortin) for Active External Rotation</title>
        <description>VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain). Change = (Day 22 score -- baseline score).</description>
        <time_frame>Baseline to Day 22</time_frame>
        <population>Per protocol population</population>
        <group_list>
          <group group_id="O1">
            <title>Traumeel S Inj.</title>
            <description>Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
          <group group_id="O2">
            <title>Fortecortin/Dexamethasone 8 mg Inj</title>
            <description>Fortecortin/Dexamethasone 8 mg/2 ml inj. subacromial 3 times at days 1, 8 and 15</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Abduction Rotation Pain VAS at Visit 5 (Day 22) (Traumeel® S Injections Versus Fortecortin) for Active External Rotation</title>
          <description>VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain). Change = (Day 22 score -- baseline score).</description>
          <population>Per protocol population</population>
          <units>units on a scale (mm)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="58"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-18.7" spread="21.49"/>
                    <measurement group_id="O2" value="-27.2" spread="23.44"/>
                  </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>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>All statistical analyses were of exploratory nature. A one-sided test of non-inferiority of Traumeel®S with respect to dexamethasone at level 0.025 was computed using an analysis of covariance (ANCOVA) model with treatment group as qualitative factor and the baseline value of the abduction rotation pain VAS for active external rotation as a covariate. The test decision was based on a one-sided 97.5% confidence interval . The non-inferiority margin was set to 13 mm on a 0-100 mm VAS scale.</non_inferiority_desc>
            <p_value>&lt;0.05</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>13</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>13</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>1-Sided</ci_n_sides>
            <ci_upper_limit>97.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Abduction Rotation Pain VAS for Active External Rotation - Comparison With Placebo Visit 5 (Day 22)</title>
        <description>VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain).</description>
        <time_frame>Baseline vs. Day 22</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Traumeel S Inj.</title>
            <description>Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
          <group group_id="O2">
            <title>Saline Inj</title>
            <description>Saline inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Abduction Rotation Pain VAS for Active External Rotation - Comparison With Placebo Visit 5 (Day 22)</title>
          <description>VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain).</description>
          <units>Change in mm baseline vs. day 22</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-18.7" spread="21.49"/>
                    <measurement group_id="O2" value="-17.1" spread="23.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Abduction Rotation Pain VAS for Active External Rotation - Comparison With Placebo Visit 7 (Day 105)</title>
        <description>VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain).</description>
        <time_frame>Baseline vs. Day 105</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Traumeel S Inj.</title>
            <description>Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
          <group group_id="O2">
            <title>Saline Inj</title>
            <description>Saline inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Abduction Rotation Pain VAS for Active External Rotation - Comparison With Placebo Visit 7 (Day 105)</title>
          <description>VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain).</description>
          <units>units on a scale, mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-32.2" spread="26.59"/>
                    <measurement group_id="O2" value="-30.1" spread="27.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Abduction Rotation Pain VAS for Active External Rotation - Comparison With Fortecortin at Visit 7 (Day 105)</title>
        <description>VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain).</description>
        <time_frame>Baseline vs. day 105</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Traumeel S Inj.</title>
            <description>Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
          <group group_id="O2">
            <title>Fortecortin/Dexamethasone 8 mg Inj</title>
            <description>Fortecortin/Dexamethasone 8 mg/2 ml inj. subacromial 3 times at days 1, 8 and 15</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Abduction Rotation Pain VAS for Active External Rotation - Comparison With Fortecortin at Visit 7 (Day 105)</title>
          <description>VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain).</description>
          <units>units on a scale, mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="58"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-32.2" spread="26.59"/>
                    <measurement group_id="O2" value="-33.3" spread="28.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 5 (Day 22), Traumeel vs Placebo</title>
        <description>Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees.</description>
        <time_frame>Baseline vs. Day 22</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Traumeel S Inj.</title>
            <description>Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
          <group group_id="O2">
            <title>Saline Inj</title>
            <description>Saline inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
        </group_list>
        <measure>
          <title>Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 5 (Day 22), Traumeel vs Placebo</title>
          <description>Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees.</description>
          <units>degrees</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.3" spread="15.73"/>
                    <measurement group_id="O2" value="13.5" spread="18.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 7 (Day 105), Traumeel vs Placebo</title>
        <description>Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees.</description>
        <time_frame>Baseline vs. day 105</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Traumeel S Inj.</title>
            <description>Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
          <group group_id="O2">
            <title>Saline Inj</title>
            <description>Saline inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
        </group_list>
        <measure>
          <title>Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 7 (Day 105), Traumeel vs Placebo</title>
          <description>Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees.</description>
          <units>degrees</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.9" spread="19.97"/>
                    <measurement group_id="O2" value="20.0" spread="20.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 5 (Day 22) Traumeel vs Fortecortin</title>
        <description>Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees.</description>
        <time_frame>Baseline vs. Day 22</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Traumeel S Inj.</title>
            <description>Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
          <group group_id="O2">
            <title>Fortecortin/Dexamethasone 8 mg Inj</title>
            <description>Fortecortin/Dexamethasone 8 mg/2 ml inj. subacromial 3 times at days 1, 8 and 15</description>
          </group>
        </group_list>
        <measure>
          <title>Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 5 (Day 22) Traumeel vs Fortecortin</title>
          <description>Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees.</description>
          <units>degrees</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="58"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.3" spread="15.73"/>
                    <measurement group_id="O2" value="17.2" spread="21.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 7 (Day 105), Traumeel vs Fortecortin</title>
        <description>Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees.</description>
        <time_frame>Baseline vs. Day 105</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Traumeel S Inj.</title>
            <description>Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
          <group group_id="O2">
            <title>Fortecortin/Dexamethasone 8 mg Inj</title>
            <description>Fortecortin/Dexamethasone 8 mg/2 ml inj. subacromial 3 times at days 1, 8 and 15</description>
          </group>
        </group_list>
        <measure>
          <title>Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 7 (Day 105), Traumeel vs Fortecortin</title>
          <description>Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees.</description>
          <units>degrees</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="58"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.9" spread="19.97"/>
                    <measurement group_id="O2" value="17.3" spread="20.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Jobe Test at Visit 5 (Day 15) With Measurement of Pain</title>
        <description>This test looked for pain and weakness and was to be examined as active movement. Patients have to stand with shoulders in 90 degrees of abduction, 30 degrees of forward flexion and then internally rotating arm completely i.e., thumb pointing down. This was done to see if the patient was able to resist the clinician's attempts to depress the upper arm to look for muscle weakness.</description>
        <time_frame>Baseline vs. Day 22</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Traumeel S Inj.</title>
            <description>Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
          <group group_id="O2">
            <title>Fortecortin/Dexamethasone 8 mg Inj</title>
            <description>Fortecortin/Dexamethasone 8 mg/2 ml inj. subacromial 3 times at days 1, 8 and 15</description>
          </group>
          <group group_id="O3">
            <title>Saline Inj.</title>
            <description>Saline inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
        </group_list>
        <measure>
          <title>Jobe Test at Visit 5 (Day 15) With Measurement of Pain</title>
          <description>This test looked for pain and weakness and was to be examined as active movement. Patients have to stand with shoulders in 90 degrees of abduction, 30 degrees of forward flexion and then internally rotating arm completely i.e., thumb pointing down. This was done to see if the patient was able to resist the clinician's attempts to depress the upper arm to look for muscle weakness.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="58"/>
                <count group_id="O3" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                    <measurement group_id="O2" value="27"/>
                    <measurement group_id="O3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Jobe Test at Visit 5 (Day 22) With Measurement of Weakness</title>
        <description>This test looked for pain and weakness and was to be examined as active movement. Patients have to stand with shoulders in 90 degrees of abduction, 30 degrees of forward flexion and then internally rotating arm completely i.e., thumb pointing down. This was done to see if the patient was able to resist the clinician's attempts to depress the upper arm to look for muscle weakness.</description>
        <time_frame>Baseline vs. day 22</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Traumeel S Inj.</title>
            <description>Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
          <group group_id="O2">
            <title>Fortecortin/Dexamethasone 8 mg Inj</title>
            <description>Fortecortin/Dexamethasone 8 mg/2 ml inj. subacromial 3 times at days 1, 8 and 15</description>
          </group>
          <group group_id="O3">
            <title>Saline Inj.</title>
            <description>Saline inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
        </group_list>
        <measure>
          <title>Jobe Test at Visit 5 (Day 22) With Measurement of Weakness</title>
          <description>This test looked for pain and weakness and was to be examined as active movement. Patients have to stand with shoulders in 90 degrees of abduction, 30 degrees of forward flexion and then internally rotating arm completely i.e., thumb pointing down. This was done to see if the patient was able to resist the clinician's attempts to depress the upper arm to look for muscle weakness.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="58"/>
                <count group_id="O3" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="19"/>
                    <measurement group_id="O3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Painful Arc Test at Visit 5 (Day 22)</title>
        <description>The amount of pain that disappeared by further abduction in the range between 60° and 120° was to be measured, with measurement of pain being positive/negative. The idea behind the test is the subacromial space in abduction becomes smaller, whereby compression of the rotator cuff and the subacromial bursa occurs (impingement test).</description>
        <time_frame>Baseline vs. day 22</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Traumeel S Inj.</title>
            <description>Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
          <group group_id="O2">
            <title>Fortecortin/Dexamethasone 8 mg Inj</title>
            <description>Fortecortin/Dexamethasone 8 mg/2 ml inj. subacromial 3 times at days 1, 8 and 15</description>
          </group>
          <group group_id="O3">
            <title>Saline Inj.</title>
            <description>Saline inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
        </group_list>
        <measure>
          <title>Painful Arc Test at Visit 5 (Day 22)</title>
          <description>The amount of pain that disappeared by further abduction in the range between 60° and 120° was to be measured, with measurement of pain being positive/negative. The idea behind the test is the subacromial space in abduction becomes smaller, whereby compression of the rotator cuff and the subacromial bursa occurs (impingement test).</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="58"/>
                <count group_id="O3" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                    <measurement group_id="O2" value="30"/>
                    <measurement group_id="O3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in DASH at Visit 5 (Day 22)</title>
        <description>The score from the questions answered on the DASH (Disaability of the Arm, Shoulder and Hand) questionnaire were evaluated on both shoulders at screening and on the target shoulder at the later visits. Any changes between the score from baseline was used to evaluate efficacy.&#xD;
The score consists of a basic questionnaire of 30 questions regarding the daily activities with the answer options from &quot;no difficulty&quot; (value 1) to &quot;unable&quot; (value 5).&#xD;
The calculation is: ((sum of values of responses/number of responses)-1) X 25. Best possible result is 0, worst possible result is 100. The score may not be calculated if there are more than 3 missing answers.</description>
        <time_frame>Baseline vs. Day 22</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Traumeel S Inj.</title>
            <description>Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
          <group group_id="O2">
            <title>Fortecortin/Dexamethasone 8 mg Inj</title>
            <description>Fortecortin/Dexamethasone 8 mg/2 ml inj. subacromial 3 times at days 1, 8 and 15</description>
          </group>
          <group group_id="O3">
            <title>Saline Inj.</title>
            <description>Saline inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in DASH at Visit 5 (Day 22)</title>
          <description>The score from the questions answered on the DASH (Disaability of the Arm, Shoulder and Hand) questionnaire were evaluated on both shoulders at screening and on the target shoulder at the later visits. Any changes between the score from baseline was used to evaluate efficacy.&#xD;
The score consists of a basic questionnaire of 30 questions regarding the daily activities with the answer options from &quot;no difficulty&quot; (value 1) to &quot;unable&quot; (value 5).&#xD;
The calculation is: ((sum of values of responses/number of responses)-1) X 25. Best possible result is 0, worst possible result is 100. The score may not be calculated if there are more than 3 missing answers.</description>
          <units>DASH 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="58"/>
                <count group_id="O2" value="58"/>
                <count group_id="O3" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.00" spread="13.648"/>
                    <measurement group_id="O2" value="-18.03" spread="19.230"/>
                    <measurement group_id="O3" value="-12.59" spread="17.698"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in DASH at Visit 7 (Day 105)</title>
        <description>The score from the questions answered on the DASH (Disaability of the Arm, Shoulder and Hand) questionnaire were evaluated on both shoulders at screening and on the The score consists of a basic questionnaire of 30 questions regarding the daily activities with the answer options from &quot;no difficulty&quot; (value 1) to &quot;unable&quot; (value 5).&#xD;
The calculation is: ((sum of values of responses/number of responses)-1) X 25. Best possible result is 0, worst possible result is 100. The score may not be calculated if there are more than 3 missing answers.target shoulder at the later visits. Any changes between the score from baseline was used to evaluate efficacy</description>
        <time_frame>Baseline vs. Day 105</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Traumeel S Inj.</title>
            <description>Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
          <group group_id="O2">
            <title>Fortecortin/Dexamethasone 8 mg Inj</title>
            <description>Fortecortin/Dexamethasone 8 mg/2 ml inj. subacromial 3 times at days 1, 8 and 15</description>
          </group>
          <group group_id="O3">
            <title>Saline Inj.</title>
            <description>Saline inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in DASH at Visit 7 (Day 105)</title>
          <description>The score from the questions answered on the DASH (Disaability of the Arm, Shoulder and Hand) questionnaire were evaluated on both shoulders at screening and on the The score consists of a basic questionnaire of 30 questions regarding the daily activities with the answer options from &quot;no difficulty&quot; (value 1) to &quot;unable&quot; (value 5).&#xD;
The calculation is: ((sum of values of responses/number of responses)-1) X 25. Best possible result is 0, worst possible result is 100. The score may not be calculated if there are more than 3 missing answers.target shoulder at the later visits. Any changes between the score from baseline was used to evaluate efficacy</description>
          <units>DASH 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="58"/>
                <count group_id="O2" value="58"/>
                <count group_id="O3" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-20.91" spread="19.747"/>
                    <measurement group_id="O2" value="-22.07" spread="27.697"/>
                    <measurement group_id="O3" value="-19.77" spread="20.802"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events have been collected for 15 months between 16.Apr.2013 (first Patient in) and 23.Jun.2014 (last Patient out).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Traumeel S Inj.</title>
          <description>Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
        </group>
        <group group_id="E2">
          <title>Fortecortin/Dexamethasone 8 mg Inj</title>
          <description>Fortecortin/Dexamethasone 8 mg/2 ml inj. subacromial 3 times at days 1, 8 and 15</description>
        </group>
        <group group_id="E3">
          <title>Saline Inj.</title>
          <description>Saline inj. 2 ml. subacromial 3 times at days 1, 8 and 15</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (16.0)</default_vocab>
        <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="0" subjects_at_risk="72"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Auricular fibrillation</sub_title>
                <description>The event was severe and led to discontinuation of study drug after the first injection.&#xD;
The patient had a medical history of a previous event of auricular fibrillation since 2002.&#xD;
Both investigator and Heel considered the SAE as &quot;unrelated&quot;.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="67"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (16.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="72"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="72"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="72"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="67"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="36"/>
              </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>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr Istvan Zatik</name_or_title>
      <organization>Biologische Heilmittel Heel</organization>
      <phone>+497221501(0) ext 3192</phone>
      <email>istvan.zatik@heel.com</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/NCT01702233
org study id: TRARO
secondary id: 2012-003393-12
nct id: NCT01702233
lead sponsor: 
has dmc: No
To evaluate functional, clinical, and subjective parameters in patients with rotator cuff
      syndrome and bursitis treated with Traumeel® S injections versus corticosteroid injections
      and versus placebo. 160 patients are planned to be randomised (i.e., 64 patients per active
      treatment group and 32 patients in the placebo group) in 9 investigator sites in Germany,
      Belgium and Spain.

      Finally 176 patients have been randomized (73 Traumeel, 67 Fortecortin and 36 Placebo) and
      175 of them received at least one dosage of treatment
Duration of the study were 16 weeks. Duration of Treatments were 15 days, applying one
      injection of 2 ml od study medication at days 1, 8, and 15. There was a follow up visit at
      day 22 (Primary endpoint), a telephone visit at week 9 and a final visit at week 15.

      Standard descriptive summary statistics were calculated for continuous variables (i.e.
      arithmetic mean, standard deviation, minimum value, median, maximum value, number of
      non-missing values). All statistical analyses in this study were of exploratory nature. The
      summaries of the efficacy parameters, the statistical analyses of the primary efficacy
      variable, and the statistical analyses of the secondary efficacy variables were performed on
      the PP Set. These summaries and analyses were supported by corresponding summaries and
      exploratory statistical analyses performed on the Full Analysis Set. Missing values for all
      efficacy parameters were imputed by the last observation carried forward (LOCF) approach. The
      Modified Per-Protocol (MPP) Set excluded from the PP Set also all patients having taken
      unallowed concomitant medication after Visit 5 and was used as a secondary population for the
      analysis of efficacy. All statistical tests were two-sided with a significance level of
      (alpha) = 0.05, unless specified otherwise. The primary efficacy variable was the change from
      baseline in VAS for abduction rotation pain at Visit 5 (Day 22) (Traumeel® S injections
      versus corticoid injections) for active external rotation.

      A one-sided test of non-inferiority of Traumeel® S with respect to dexamethasone at level
      0.025 was computed using an analysis of covariance (ANCOVA) model with treatment group as
      qualitative factor and the baseline value of the abduction rotation pain VAS for active
      external rotation as a covariate. The test decision was based on a one-sided 97.5% confidence
      interval for the corresponding treatment difference. The non-inferiority margin was set to 13
      mm on a 0 - 100 mm VAS scale.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change From Baseline in Abduction Rotation Pain VAS at Visit 5 (Day 22) (Traumeel® S Injections Versus Fortecortin) for Active External Rotation
time frame: Baseline to Day 22
description: VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain). Change = (Day 22 score -- baseline score).
measure: Change From Baseline in Abduction Rotation Pain VAS for Active External Rotation - Comparison With Placebo Visit 5 (Day 22)
time frame: Baseline vs. Day 22
description: VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain).
measure: Change From Baseline in Abduction Rotation Pain VAS for Active External Rotation - Comparison With Placebo Visit 7 (Day 105)
time frame: Baseline vs. Day 105
description: VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain).
measure: Change From Baseline in Abduction Rotation Pain VAS for Active External Rotation - Comparison With Fortecortin at Visit 7 (Day 105)
time frame: Baseline vs. day 105
description: VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain).
measure: Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 5 (Day 22), Traumeel vs Placebo
time frame: Baseline vs. Day 22
description: Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees.
measure: Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 7 (Day 105), Traumeel vs Placebo
time frame: Baseline vs. day 105
description: Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees.
measure: Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 5 (Day 22) Traumeel vs Fortecortin
time frame: Baseline vs. Day 22
description: Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees.
measure: Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 7 (Day 105), Traumeel vs Fortecortin
time frame: Baseline vs. Day 105
description: Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees.
measure: Jobe Test at Visit 5 (Day 15) With Measurement of Pain
time frame: Baseline vs. Day 22
description: This test looked for pain and weakness and was to be examined as active movement. Patients have to stand with shoulders in 90 degrees of abduction, 30 degrees of forward flexion and then internally rotating arm completely i.e., thumb pointing down. This was done to see if the patient was able to resist the clinician's attempts to depress the upper arm to look for muscle weakness.
measure: Jobe Test at Visit 5 (Day 22) With Measurement of Weakness
time frame: Baseline vs. day 22
description: This test looked for pain and weakness and was to be examined as active movement. Patients have to stand with shoulders in 90 degrees of abduction, 30 degrees of forward flexion and then internally rotating arm completely i.e., thumb pointing down. This was done to see if the patient was able to resist the clinician's attempts to depress the upper arm to look for muscle weakness.
measure: Painful Arc Test at Visit 5 (Day 22)
time frame: Baseline vs. day 22
description: The amount of pain that disappeared by further abduction in the range between 60° and 120° was to be measured, with measurement of pain being positive/negative. The idea behind the test is the subacromial space in abduction becomes smaller, whereby compression of the rotator cuff and the subacromial bursa occurs (impingement test).
measure: Change From Baseline in DASH at Visit 5 (Day 22)
time frame: Baseline vs. Day 22
description: The score from the questions answered on the DASH (Disaability of the Arm, Shoulder and Hand) questionnaire were evaluated on both shoulders at screening and on the target shoulder at the later visits. Any changes between the score from baseline was used to evaluate efficacy.
The score consists of a basic questionnaire of 30 questions regarding the daily activities with the answer options from "no difficulty" (value 1) to "unable" (value 5).
The calculation is: ((sum of values of responses/number of responses)-1) X 25. Best possible result is 0, worst possible result is 100. The score may not be calculated if there are more than 3 missing answers.
measure: Change From Baseline in DASH at Visit 7 (Day 105)
time frame: Baseline vs. Day 105
description: The score from the questions answered on the DASH (Disaability of the Arm, Shoulder and Hand) questionnaire were evaluated on both shoulders at screening and on the The score consists of a basic questionnaire of 30 questions regarding the daily activities with the answer options from "no difficulty" (value 1) to "unable" (value 5).
The calculation is: ((sum of values of responses/number of responses)-1) X 25. Best possible result is 0, worst possible result is 100. The score may not be calculated if there are more than 3 missing answers.target shoulder at the later visits. Any changes between the score from baseline was used to evaluate efficacy
arm group label: Traumeel S inj.
arm group type: Experimental
description: Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15
arm group label: Fortecortin/Dexamethasone 8 mg inj
arm group type: Active Comparator
description: Fortecortin/Dexamethasone 8 mg/2 ml inj. subacromial 3 times at days 1, 8 and 15
arm group label: Saline inj.
arm group type: Placebo Comparator
description: Saline inj. 2 ml. subacromial 3 times at days 1, 8 and 15
intervention type: Drug
intervention name: Traumeel S inj
description: Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15
arm group label: Traumeel S inj.
other name: Traumeel
intervention type: Drug
intervention name: Fortecortin/Dexamethasone 8 mg/2 ml inj
description: Fortecortin/Dexamethasone 8 mg/2 ml inj. subacromial 3 times at days 1, 8 and 15
arm group label: Fortecortin/Dexamethasone 8 mg inj
other name: Dexamethasone 8 mg
intervention type: Drug
intervention name: Saline inj
description: Saline inj. 2 ml. subacromial 3 times at days 1, 8 and 15
arm group label: Saline inj.
other name: Placebo inj
criteria: 
gender: All
minimum age: 40 Years
maximum age: 65 Years
healthy volunteers: No
last name: Luc Vandenbossche, MD, PhD
role: Principal Investigator
affiliation: Physical and Rehabilitation Medicine University Ghent, BE
facility: 
country: Belgium
responsible party type: Sponsor
mesh term: Bursitis
mesh term: Syndrome
mesh term: Rotator Cuff Injuries
mesh term: Dexamethasone
mesh term: Dexamethasone acetate
mesh term: BB 1101
sharing ipd: Undecided
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 