Comparing the Incidence of Preeclampsia Between Pregnant Women Receiving Tdap Vaccinations at Week 28 or at Week 36

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Pre-Eclampsia, Diphtheria, Tetanus and Pertussis Vaccine Reaction

Intervention / Treatment
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* Drug: Tdap Vaccine Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: confirmed pregnancy at week 12 Age 18 to 42 Willing to participate and sign informed consent documentation willing to follow study procedures with regards to randomization of Tdap and attend all routine clinic visits per obstetrician and standard of care accept Tdap vaccination either at week 28 or week 36 Exclusion Criteria: no history of allergic reaction or intolerance to Tdap vaccination No history of cancer in past 5 years prior to this study (except for non melanoma localized skin cancers or cancer in situ) -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 42 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tdap vaccinations at gestational week 28<br>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 | Drug: Tdap Vaccine Administration<br>* 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%<br>|
| Active Comparator: Tdap vaccinations at gestational week 36<br>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 | Drug: Tdap Vaccine Administration<br>* 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%<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of preeclampsia in each arm of the study with regards to timing of Tdap vaccination | The definition of preeclampsia in this study will follow the guidelines of ACOG inclusive of hypertension, proteinuria, but also other features | Through duration of pregnancy approximately 10 months | 
| Incidence of preeclampsia in each arm of the study with regards to the quantitative anti-tetanus toxoid antibody level | 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 | Through duration of pregnancy approximately 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of other potential risk factors for preeclampsia inclusive of BMI, hypertension, prior history of preeclampsia, first pregnancy | Statistical analysis of all possible variables for preeclampsia | Through duration of pregnancy approximately 10 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Preeclampsia, Tdap vaccinations