<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/NCT04424693</url>
  </required_header>
  <id_info>
    <org_study_id>PE-Tdap01</org_study_id>
    <nct_id>NCT04424693</nct_id>
  </id_info>
  <brief_title>Comparing the Incidence of Preeclampsia Between Pregnant Women Receiving Tdap Vaccinations at Week 28 or at Week 36</brief_title>
  <official_title>A Prospective Randomized Clinical Research Trial Comparing the Incidence of Preeclampsia Between Pregnant Women Receiving Tdap Vaccinations at Week 28 and Those Receiving Tdap Vaccinations at Week 36</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Arthritis Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Louisiana State University Health Sciences Center in New Orleans</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Brigham Young University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Institute of Arthritis Research</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Preeclampsia is a significant medical condition occurring in 3-8% of pregnancies and impacts&#xD;
      deleteriously both maternal and fetal health. An important discovery has been made by Dr&#xD;
      Craig D Scoville showing that early Tdap vaccinations in pregnancy can reduce the incidence&#xD;
      of preeclampsia by more than 50%. A prospective clinical research trial is proposed and&#xD;
      urgently needed to validate this finding and thereby make a significant contribution in&#xD;
      reducing the incidence of this common and severe complication of pregnancy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A double blinded randomized prospective clinical research study is proposed to validate the&#xD;
      hypothesis that Tdap vaccinations at week 28 in pregnancy can reduce the incidence of&#xD;
      preeclampsia by more than 50%. This project will recruit 1600 pregnant women with appropriate&#xD;
      informed consent in the first trimester of pregnancy, obtain detailed obstetric and health&#xD;
      history, and then randomize these subjects so 800 women receive Tdap at week 28, and 800&#xD;
      women receive Tdap at week 36, and all women will be followed during their pregnancies using&#xD;
      standard of care with special attention to preeclampsia and fetal outcomes. Blood samples&#xD;
      will be obtained at weeks 12, 20, and 36 in order to test the anti-tetanus toxoid antibody&#xD;
      levels, anti-diptheria antibody levels, anti-pertussis antibody levels, and also maternal&#xD;
      cytokines (IL-2, IL-4, IL-6, IL-10, TNFa, IL-17, and IFNg), and placental biomarkers (sFlt-1,&#xD;
      sEng, and PIGF) for preeclampsia on those patients who develop preeclampsia and compare to&#xD;
      those who didn't and thereby better understand the biomarkers of preeclampsia and devise a&#xD;
      better formula for positive prediction for preeclampsia. To make this change in clinical&#xD;
      practice and save lives, this study is asking for funding from NICHD PA-18-480.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">December 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2023</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>Parallel Assignment</intervention_model>
    <intervention_model_description>Pregnant women enlisted in the double blinded study will be randomized to receive Tdap vaccination either at week 28 or week 36 and observed and treated with standard of care.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Each study site will designate an &quot;injection nurse&quot; who will be responsible for preparing both placebo and Tdap administration and will be the only one knowing when a patient gets either Tdap injection at week 28 or placebo injection at week 28, or gets Tdap injection at week 36 or placebo injection at week 36. This person will be the only one at each site who will know the randomization of each subject and is the only one who will administer the injection. Every subject will receive Tdap either at week 28 or week 36 and receive placebo injection on the other injection time.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of preeclampsia in each arm of the study with regards to timing of Tdap vaccination</measure>
    <time_frame>Through duration of pregnancy approximately 10 months</time_frame>
    <description>The definition of preeclampsia in this study will follow the guidelines of ACOG inclusive of hypertension, proteinuria, but also other features</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of preeclampsia in each arm of the study with regards to the quantitative anti-tetanus toxoid antibody level</measure>
    <time_frame>Through duration of pregnancy approximately 10 months</time_frame>
    <description>Test the hypothesis that pregnant women with anti-tetanus toxoid antibody levels &lt;1.0 IU/ml are at higher risk of preeclampsia compared to those with higher levels. Obtain blood levels for anti-tetanus toxoid antibody levels, anti-pertussis antibody levels, and anti-diptheria antibody levels will be tested at weeks 12, 20, and 36</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessment of other potential risk factors for preeclampsia inclusive of BMI, hypertension, prior history of preeclampsia, first pregnancy</measure>
    <time_frame>Through duration of pregnancy approximately 10 months</time_frame>
    <description>Statistical analysis of all possible variables for preeclampsia</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Compare the placental and maternal biomarkers of preeclampsia in order to devise a better formula for positive prediction of preeclampsia</measure>
    <time_frame>Through duration of pregnancy at 12, 20 and 36 week of gestation</time_frame>
    <description>Follow the quantitative levels of maternal cytokines in pg/ml: IL-2, IL-4, IL-6, IL-10, TNFa, IL-17, IFNg and placental biomarkers in pg/ml PIGF during pregnancy at weeks 12, 20, and 36 and compare these levels with those women who develop preeclampsia to normal pregnancy cohorts from this study during the same times tested</description>
  </other_outcome>
  <other_outcome>
    <measure>Compare the placental and maternal biomarkers of preeclampsia in order to devise a better formula for positive prediction of preeclampsia</measure>
    <time_frame>Through duration of pregnancy at 12, 20 and 36 week of gestation</time_frame>
    <description>Follow the quantitative levels of maternal placental biomarkers in ng/ml sFlt-1 and sEng during pregnancy at weeks 12, 20, and 36 and compare these levels with those women who develop preeclampsia to normal pregnancy cohorts from this study during the same times tested</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">1600</enrollment>
  <condition>Pre-Eclampsia</condition>
  <condition>Diphtheria, Tetanus and Pertussis Vaccine Reaction</condition>
  <arm_group>
    <arm_group_label>Tdap vaccinations at gestational week 28</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pregnant women entering into this clinical research study and signing informed consent at week 12 will be randomized to either receive Tdap vaccination at week 28 or week 36. Subjects receiving Tdap vaccination at week 28 will receive a placebo injection at week 36. Subject will be followed with routine standard of care throughout their pregnancy and have routine clinic visits from which study visits will include weeks 12, 20, 28, 36, and 2 weeks postpartum. Data will be collected at each of these visits with special attention to the development of preeclampsia and fetal health</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tdap vaccinations at gestational week 36</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pregnant women entering into this clinical research study and signing informed consent at week 12 will be randomized to either receive Tdap vaccination at week 28 or week 36. Subjects receiving Tdap vaccination at week 36 will receive a placebo injection at week 28. Subjects will be followed with routine standard of care throughout their pregnancy and have routine clinic visits from which study visits will include weeks 12, 20, 28, 36, and 2 weeks postpartum. Data will be collected at each of these visits with special attention to the development of preeclampsia and fetal health</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tdap Vaccine Administration</intervention_name>
    <description>Tdap vaccinations are routinely given during pregnancy between weeks 27 and 36 per guidelines of American College Obstetrics and Gynecology (ACOG) -- but this study uniquely is trying to establish that the earlier Tdap vaccinations reduce preeclampsia by more than 50%</description>
    <arm_group_label>Tdap vaccinations at gestational week 28</arm_group_label>
    <arm_group_label>Tdap vaccinations at gestational week 36</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. confirmed pregnancy at week 12&#xD;
&#xD;
          2. Age 18 to 42&#xD;
&#xD;
          3. Willing to participate and sign informed consent documentation&#xD;
&#xD;
          4. willing to follow study procedures with regards to randomization of Tdap and attend&#xD;
             all routine clinic visits per obstetrician and standard of care&#xD;
&#xD;
          5. accept Tdap vaccination either at week 28 or week 36&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. no history of allergic reaction or intolerance to Tdap vaccination&#xD;
&#xD;
          2. No history of cancer in past 5 years prior to this study (except for non melanoma&#xD;
             localized skin cancers or cancer in situ) -&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Pregnant women</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>42 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Craig D Scoville, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute of Arthritis Research</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Craig D Scoville, MD,PhD</last_name>
    <phone>208-542-9080</phone>
    <email>cdscoville@yahoo.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Maritza Rosales</last_name>
    <phone>208-542-9080</phone>
    <email>maritza@scovilleclinic.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Institute of Arthritis Research</name>
      <address>
        <city>Idaho Falls</city>
        <state>Idaho</state>
        <zip>83404</zip>
        <country>United States</country>
      </address>
    </facility>
    <contact>
      <last_name>Craig D Scoville, MD, PhD</last_name>
      <phone>208-542-9080</phone>
      <email>cdscoville@yahoo.com</email>
    </contact>
    <contact_backup>
      <last_name>Maritza Rosales</last_name>
      <phone>208-542-9080</phone>
      <email>maritza@scovilleclinic.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>June 11, 2020</last_update_submitted>
  <last_update_submitted_qc>June 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Preeclampsia</keyword>
  <keyword>Tdap vaccinations</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diphtheria</mesh_term>
    <mesh_term>Pre-Eclampsia</mesh_term>
    <mesh_term>Eclampsia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Data acquired in this project will be shared through presentations at scientific meetings and published peer reviewed publications. In order to disseminate the data, we will maintain a data archive where all information is stored and can be distributed. Data requests may be sent to the PI and reasonable requests will be granted. However a particular data set in the archives will only be shared after a manuscript describing the main findings has been accepted for publication. Also any proprietary information will not be shared until legal restrictions make it permissible</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>see Plan Description and no time limit once the data is made available to the public</ipd_time_frame>
    <ipd_access_criteria>contact Institute of Arthritis Research at scovilleclinic.com</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT04424693
org study id: PE-Tdap01
nct id: NCT04424693
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Preeclampsia is a significant medical condition occurring in 3-8% of pregnancies and impacts
      deleteriously both maternal and fetal health. An important discovery has been made by Dr
      Craig D Scoville showing that early Tdap vaccinations in pregnancy can reduce the incidence
      of preeclampsia by more than 50%. A prospective clinical research trial is proposed and
      urgently needed to validate this finding and thereby make a significant contribution in
      reducing the incidence of this common and severe complication of pregnancy.
A double blinded randomized prospective clinical research study is proposed to validate the
      hypothesis that Tdap vaccinations at week 28 in pregnancy can reduce the incidence of
      preeclampsia by more than 50%. This project will recruit 1600 pregnant women with appropriate
      informed consent in the first trimester of pregnancy, obtain detailed obstetric and health
      history, and then randomize these subjects so 800 women receive Tdap at week 28, and 800
      women receive Tdap at week 36, and all women will be followed during their pregnancies using
      standard of care with special attention to preeclampsia and fetal outcomes. Blood samples
      will be obtained at weeks 12, 20, and 36 in order to test the anti-tetanus toxoid antibody
      levels, anti-diptheria antibody levels, anti-pertussis antibody levels, and also maternal
      cytokines (IL-2, IL-4, IL-6, IL-10, TNFa, IL-17, and IFNg), and placental biomarkers (sFlt-1,
      sEng, and PIGF) for preeclampsia on those patients who develop preeclampsia and compare to
      those who didn't and thereby better understand the biomarkers of preeclampsia and devise a
      better formula for positive prediction for preeclampsia. To make this change in clinical
      practice and save lives, this study is asking for funding from NICHD PA-18-480.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Pregnant women enlisted in the double blinded study will be randomized to receive Tdap vaccination either at week 28 or week 36 and observed and treated with standard of care.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Each study site will designate an "injection nurse" who will be responsible for preparing both placebo and Tdap administration and will be the only one knowing when a patient gets either Tdap injection at week 28 or placebo injection at week 28, or gets Tdap injection at week 36 or placebo injection at week 36. This person will be the only one at each site who will know the randomization of each subject and is the only one who will administer the injection. Every subject will receive Tdap either at week 28 or week 36 and receive placebo injection on the other injection time.
measure: Incidence of preeclampsia in each arm of the study with regards to timing of Tdap vaccination
time frame: Through duration of pregnancy approximately 10 months
description: The definition of preeclampsia in this study will follow the guidelines of ACOG inclusive of hypertension, proteinuria, but also other features
measure: Incidence of preeclampsia in each arm of the study with regards to the quantitative anti-tetanus toxoid antibody level
time frame: Through duration of pregnancy approximately 10 months
description: Test the hypothesis that pregnant women with anti-tetanus toxoid antibody levels <1.0 IU/ml are at higher risk of preeclampsia compared to those with higher levels. Obtain blood levels for anti-tetanus toxoid antibody levels, anti-pertussis antibody levels, and anti-diptheria antibody levels will be tested at weeks 12, 20, and 36
measure: Assessment of other potential risk factors for preeclampsia inclusive of BMI, hypertension, prior history of preeclampsia, first pregnancy
time frame: Through duration of pregnancy approximately 10 months
description: Statistical analysis of all possible variables for preeclampsia
measure: Compare the placental and maternal biomarkers of preeclampsia in order to devise a better formula for positive prediction of preeclampsia
time frame: Through duration of pregnancy at 12, 20 and 36 week of gestation
description: Follow the quantitative levels of maternal cytokines in pg/ml: IL-2, IL-4, IL-6, IL-10, TNFa, IL-17, IFNg and placental biomarkers in pg/ml PIGF during pregnancy at weeks 12, 20, and 36 and compare these levels with those women who develop preeclampsia to normal pregnancy cohorts from this study during the same times tested
measure: Compare the placental and maternal biomarkers of preeclampsia in order to devise a better formula for positive prediction of preeclampsia
time frame: Through duration of pregnancy at 12, 20 and 36 week of gestation
description: Follow the quantitative levels of maternal placental biomarkers in ng/ml sFlt-1 and sEng during pregnancy at weeks 12, 20, and 36 and compare these levels with those women who develop preeclampsia to normal pregnancy cohorts from this study during the same times tested
arm group label: Tdap vaccinations at gestational week 28
arm group type: Active Comparator
description: Pregnant women entering into this clinical research study and signing informed consent at week 12 will be randomized to either receive Tdap vaccination at week 28 or week 36. Subjects receiving Tdap vaccination at week 28 will receive a placebo injection at week 36. Subject will be followed with routine standard of care throughout their pregnancy and have routine clinic visits from which study visits will include weeks 12, 20, 28, 36, and 2 weeks postpartum. Data will be collected at each of these visits with special attention to the development of preeclampsia and fetal health
arm group label: Tdap vaccinations at gestational week 36
arm group type: Active Comparator
description: Pregnant women entering into this clinical research study and signing informed consent at week 12 will be randomized to either receive Tdap vaccination at week 28 or week 36. Subjects receiving Tdap vaccination at week 36 will receive a placebo injection at week 28. Subjects will be followed with routine standard of care throughout their pregnancy and have routine clinic visits from which study visits will include weeks 12, 20, 28, 36, and 2 weeks postpartum. Data will be collected at each of these visits with special attention to the development of preeclampsia and fetal health
intervention type: Drug
intervention name: Tdap Vaccine Administration
description: Tdap vaccinations are routinely given during pregnancy between weeks 27 and 36 per guidelines of American College Obstetrics and Gynecology (ACOG) -- but this study uniquely is trying to establish that the earlier Tdap vaccinations reduce preeclampsia by more than 50%
arm group label: Tdap vaccinations at gestational week 28
arm group label: Tdap vaccinations at gestational week 36
criteria: 
gender: Female
gender based: Yes
gender description: Pregnant women
minimum age: 18 Years
maximum age: 42 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Craig D Scoville, MD, PhD
role: Principal Investigator
affiliation: Institute of Arthritis Research
last name: Craig D Scoville, MD,PhD
phone: 208-542-9080
email: cdscoville@yahoo.com
last name: Maritza Rosales
phone: 208-542-9080
email: maritza@scovilleclinic.com
facility: 
contact: 
contact backup: 
country: United States
responsible party type: Sponsor
mesh term: Diphtheria
mesh term: Pre-Eclampsia
mesh term: Eclampsia
sharing ipd: Yes
ipd description: Data acquired in this project will be shared through presentations at scientific meetings and published peer reviewed publications. In order to disseminate the data, we will maintain a data archive where all information is stored and can be distributed. Data requests may be sent to the PI and reasonable requests will be granted. However a particular data set in the archives will only be shared after a manuscript describing the main findings has been accepted for publication. Also any proprietary information will not be shared until legal restrictions make it permissible
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: see Plan Description and no time limit once the data is made available to the public
ipd access criteria: contact Institute of Arthritis Research at scovilleclinic.com