Clinical trial NCT04705116: COVID-19 Vaccines International Pregnancy Exposure Registry
Official title: COVID-19 Vaccines International Pregnancy Exposure Registry (C-VIPER)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Covid19
Lead sponsor: Pregistry
Sponsor class: INDUSTRY
First posted: 2021-01-12
Enrollment: 6000
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The target study population consists of pregnant women who are 18 years of age and older. The exposed group (Cohort 1) includes pregnant women who received at least one dose of a COVID-19 vaccine from 30 days prior to the first day of the LMP to end of pregnancy. The reference group (Cohort 2) includes pregnant women who have not received a COVID-19 vaccine during pregnancy. Women vaccinated against COVID-19 before 30 days prior to the first day of the LMP are eligible in the reference group. Both cohorts will be matched by country of residence and gestational age at enrollment (±2 weeks).

Brief summary: The objective of the COVID-19 Vaccines International Pregnancy Exposure Registry (C-VIPER) is to evaluate obstetric, neonatal, and infant outcomes among women vaccinated during pregnancy with a COVID-19 vaccine.

Specifically, the C-VIPER will estimate the risk of obstetric outcomes (spontaneous abortion, antenatal bleeding, gestational diabetes, gestational hypertension, intrauterine growth restriction, postpartum hemorrhage, fetal distress, uterine rupture, placenta previa, chorioamnionitis, Caesarean delivery, COVID-19), neonatal outcomes (major congenital malformations, low birth weight, neonatal death, neonatal encephalopathy, neonatal infections, neonatal acute kidney injury, preterm birth, respiratory distress in the newborn, small for gestational age, stillbirth, COVID-19), and infant outcomes (developmental milestones \[motor, cognitive, language, social-emotional, and mental health skills\], height, weight, failure to thrive, medical conditions during the first 12 months of life, COVID-19) among pregnant women exposed to single (homologous) or mixed (heterologous) COVID-19 vaccine brand series from 30 days prior to the first day of the last menstrual period to end of pregnancy and their offspring relative to a matched reference group who received no COVID-19 vaccines during pregnancy.

Detailed description: Rationale and background: COVID-19 vaccines will be used in pregnant populations. Scientific evidence regarding their safety for pregnant women and the developing fetus is lacking.

Objective: The objective of the COVID-19 Vaccines International Pregnancy Exposure Registry (C-VIPER) is to estimate the risk of obstetric outcomes (spontaneous abortion, antenatal bleeding, gestational diabetes, gestational hypertension, intrauterine growth restriction, postpartum hemorrhage, fetal distress, uterine rupture, placenta previa, chorioamnionitis, Caesarean delivery, COVID-19), neonatal outcomes (major congenital malformations, low birth weight, neonatal death, neonatal encephalopathy, neonatal infections, neonatal acute kidney injury, preterm birth, respiratory distress in the newborn, small for gestational age, stillbirth, COVID-19), and infant outcomes (developmental milestones \[motor, cognitive, language, social-emotional, and mental health skills\], height, weight, failure to thrive, medical conditions during the first 12 months of life, COVID-19) among pregnant women exposed to single (homologous) or mixed (heterologous) COVID-19 vaccine brand series from 30 days prior to the first day of the last menstrual period (LMP) to end of pregnancy and their offspring relative to a matched reference group who received no COVID-19 vaccines during pregnancy.

Study design: The C-VIPER is an international, non-interventional, post-marketing cohort study designed to collect prospective safety data among women vaccinated with a COVID-19 vaccine during pregnancy or within 30 days prior to the first day of the LMP.

Population: The study population includes 2 cohorts of pregnant women 18 years of age and older matched by country and gestational age (±2 weeks):

* Cohort 1: pregnant women exposed from 30 days prior to the first day of the LMP to end of pregnancy to at least one dose of a COVID-19 vaccine. These participants are enrolled as part of the C-VIPER.
* Cohort 2: pregnant women unexposed to a COVID-19 vaccine during pregnancy. These participants are enrolled through the Pregistry International Exposure Registry (PIPER) with the same methods as those in Cohort 1. Women vaccinated before 30 days prior to the first day of the LMP are eligible for inclusion.

Registration and participation via a website especially developed for the C-VIPER are voluntary. Eligible women can enroll at any time during pregnancy.

Data collection: Pregnancy data are collected at enrollment, monthly, and at the end of pregnancy. Liveborn infants are followed-up and data are collected at birth and then every three months until 12 months of age. Information is obtained directly from the participant. The C-VIPER collects data on potential confounding factors (such as maternal sociodemographic characteristics, occupation, behaviors, reproductive history, chronic conditions, results of SARS-CoV-2 tests before and during this pregnancy, new COVID-19 vaccinations, use of medications and other vaccinations, and measures of healthcare utilization), and information related to obstetric, neonatal, and infant outcomes. Given the international nature of the C-VIPER, the questionnaires are available in the languages spoken where it is conducted. Participant confidentiality and anonymity are strictly upheld.

Analysis: Exposure to the vaccine during specific etiologically relevant periods is considered when estimating the risk for each outcome (e.g., first trimester for miscarriages and malformations). Relative risks are presented unadjusted and adjusted using propensity scores (PS) to account for imbalances in characteristics between the exposed and the reference groups.

Sample size: At least 200 pregnancies exposed to each branded COVID-19 vaccine during the first trimester and 300 exposed thereafter during pregnancy are projected. For each exposed pregnancy, 2 unexposed pregnancies enrolled in the PIPER will be matched by country and gestational age at enrollment (±2 weeks).

Study Milestones: The total duration of the study will be 5 years. Obstetric, neonatal, and infant outcomes will be assessed on an ongoing basis as data become available. Data on pregnancy, neonatal and infant outcomes will be included in the interim reports as soon as available. The first two years will include, primarily, enrollment of pregnancies; the third and fourth years will involve follow-up of pregnancies and newborns; and, the final year, will be for data analyses and publications. Results on pregnancy and neonatal outcomes, even preliminary, are expected within the first year of the study. Annual and semi-annual interim reports will be submitted to the Scientific Advisory Committee (SAC) for their review and feedback as well as abbreviated quarterly progress reports summarizing cumulative results on key outcomes. A final report will be prepared at the end of the study.

Governance: The C-VIPER is conducted by Pregistry and includes an internal Safety Management Team (SMT) of experienced pharmacovigilance professionals and a dysmorphologist who meet regularly to review individual cases and safety signals. Additionally, the C-VIPER is in consultation with experts from relevant fields, such as maternal-fetal medicine, infectious diseases, epidemiology, and biostatistics from academic institutions, private practice, and/or government agencies. These individuals constitute the SAC and will provide an independent review of the C-VIPER data.

Eligibility criteria: Inclusion criteria:

Vaccinated population:

* Pregnant at time of enrollment
* Age ≥18 years at time of enrollment
* Signed the informed consent form and submitted the baseline module "COVID-19 Vaccination During This Pregnancy"
* Received at least one dose of a COVID-19 vaccine during pregnancy or within the 30 days prior to the first day of the LMP
* Resident of a country where a Central Institutional Review Board (IRB) or Ethics Committee provided approval to conduct the study or clearance that approval is not required to conduct the study

Efforts will be made to obtain documentary evidence of COVID-19 vaccination.

Comparison population:

* Pregnant at time of enrollment
* Age ≥18 years at time of enrollment
* Signed the informed consent form and submitted the minimum required data in the initial baseline questionnaire
* Have not received a COVID-19 vaccine during pregnancy or within the 30 days prior to the first day of the LMP
* Resident of a country where a Central IRB or Ethics Committee provided approval to conduct the study or clearance that approval is not required to conduct the study

Exclusion criteria:

* Not pregnant at time of enrollment
* Age \<18 years at time of enrollment

Primary outcomes:
measure: Obstetric outcomes
timeFrame: 1 year
measure: Neonatal outcomes
timeFrame: 1 year
measure: Infant weight
timeFrame: 1 year
measure: Infant developmental milestones
timeFrame: 1 year
measure: Infant COVID-19 diagnosis
timeFrame: 1 year
measure: Infant height
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Pregistry
state: California
Study officials:
affiliation: Pregistry
name: Diego Wyszynski, MD, MHS, PhD
role: PRINCIPAL_INVESTIGATOR
References: