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

Sponsor

Institute of Arthritis Research (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04424693

Collaborator

Louisiana State University Health Sciences Center in New Orleans (Other), Brigham Young University (Other)

1,600

Enrollment

Location

Arms

Anticipated Duration (Months)

32.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pre-Eclampsia Diphtheria, Tetanus and Pertussis Vaccine Reaction	Drug: Tdap Vaccine Administration	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1600 participants

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.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 (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.

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Dec 1, 2020

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Tdap vaccinations at gestational week 28 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 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%
Active Comparator: Tdap vaccinations at gestational week 36 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 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

Intervention/Treatment

Active Comparator: Tdap vaccinations at gestational week 28

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

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%

Active Comparator: Tdap vaccinations at gestational week 36

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Assessment of other potential risk factors for preeclampsia inclusive of BMI, hypertension, prior history of preeclampsia, first pregnancy [Through duration of pregnancy approximately 10 months]
Statistical analysis of all possible variables for preeclampsia

Other Outcome Measures

Compare the placental and maternal biomarkers of preeclampsia in order to devise a better formula for positive prediction of preeclampsia [Through duration of pregnancy at 12, 20 and 36 week of gestation]
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
Compare the placental and maternal biomarkers of preeclampsia in order to devise a better formula for positive prediction of preeclampsia [Through duration of pregnancy at 12, 20 and 36 week of gestation]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 42 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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) -

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institute of Arthritis Research	Idaho Falls	Idaho	United States	83404

Sponsors and Collaborators

Institute of Arthritis Research
Louisiana State University Health Sciences Center in New Orleans
Brigham Young University

Investigators

Principal Investigator: Craig D Scoville, MD, PhD, Institute of Arthritis Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Institute of Arthritis Research

ClinicalTrials.gov Identifier:

NCT04424693

Other Study ID Numbers:

PE-Tdap01

First Posted:

Jun 11, 2020

Last Update Posted:

Jun 16, 2020

Last Verified:

Jun 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Institute of Arthritis Research

Preeclampsia

Tdap vaccinations

Additional relevant MeSH terms:

Diphtheria

Pre-Eclampsia

Eclampsia

Study Results

No Results Posted as of Jun 16, 2020