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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Pre-Eclampsia; Diphtheria, Tetanus and Pertussis Vaccine Reaction
• Intervention / Treatment: Drug: Tdap Vaccine Administration

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 Type: Interventional
• Enrollment (Anticipated): 1600
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Craig D Scoville, MD,PhD; Phone Number: 208-542-9080; Email: cdscoville@yahoo.com
• Study Contact Backup: Name: Maritza Rosales; Phone Number: 208-542-9080; Email: maritza@scovilleclinic.com

Study Locations

• United States
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Institute of Arthritis Research
      • Contact: Maritza Rosales; Phone Number: 208-542-9080; Email: maritza@scovilleclinic.com
      • Contact: Craig D Scoville, MD, PhD; Phone Number: 208-542-9080; Email: cdscoville@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 42 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. confirmed pregnancy at week 12
2. Age 18 to 42
3. Willing to participate and sign informed consent documentation
4. willing to follow study procedures with regards to randomization of Tdap and attend all routine clinic visits per obstetrician and standard of care
5. accept Tdap vaccination either at week 28 or week 36

Exclusion Criteria:

1. no history of allergic reaction or intolerance to Tdap vaccination
2. No history of cancer in past 5 years prior to this study (except for non melanoma localized skin cancers or cancer in situ) -

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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%

What is the study measuring?

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

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Institute of Arthritis Research
• Collaborators: 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 record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2020
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: June 3, 2020
• First Submitted That Met QC Criteria: June 5, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): June 16, 2020
• Last Update Submitted That Met QC Criteria: June 11, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Preeclampsia; Tdap vaccinations
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Pregnancy Complications; Corynebacterium Infections; Hypertension, Pregnancy-Induced; Diphtheria; Eclampsia; Pre-Eclampsia
• Other Study ID Numbers: PE-Tdap01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan 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 Sharing Time Frame: see Plan Description and no time limit once the data is made available to the public
• IPD Sharing Access Criteria: contact Institute of Arthritis Research at scovilleclinic.com
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No