COVID-19 Vaccines International Pregnancy Exposure Registry (C-VIPER)

• ClinicalTrials.gov Identifier: NCT04705116
• Recruitment Status: Not yet recruiting
• First Posted: January 12, 2021
• Last Update Posted: January 13, 2021
• Sponsor: Pregistry
• Collaborator: Harvard School of Public Health
• Information provided by (Responsible Party): Pregistry

Study Description

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 to prevent COVID-19.

Specifically, the C-VIPER will estimate the risk of obstetric outcomes (abortion, antenatal bleeding, dysfunctional labor, gestational diabetes, hypertensive disorders of pregnancy, intrauterine growth retardation, maternal death, non-reassuring fetal status, pathways to premature birth, postpartum hemorrhage, and COVID-19), neonatal outcomes (congenital anomalies, failure to thrive, low birth weight, neonatal death, neonatal encephalopathy, neonatal infections, preterm birth, respiratory distress in the newborn, small for gestational age, stillbirth, and COVID-19), and infant outcomes (height, weight, health conditions, developmental milestones until one year of age, and COVID-19) among pregnant women exposed to a COVID-19 vaccine from 30 days prior to the first day of the last menstrual period to end of pregnancy and their offspring relative to a matched unexposed reference group.

Condition or disease	Intervention/treatment
Covid19	Biological: COVID-19 vaccine

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 relative risk of obstetric outcomes (abortion, antenatal bleeding, dysfunctional labor, gestational diabetes, hypertensive disorders of pregnancy, intrauterine growth retardation, maternal death, non-reassuring fetal status, pathways to premature birth, postpartum hemorrhage, and COVID-19), neonatal outcomes (congenital anomalies, failure to thrive, low birth weight, neonatal death, neonatal encephalopathy, neonatal infections, preterm birth, respiratory distress in the newborn, small for gestational age, stillbirth, and COVID-19), and infant outcomes (height, weight, health conditions, developmental milestones until one year of age, and COVID-19) among pregnant women exposed to a COVID-19 vaccine from 30 days prior to the first day of the last menstrual period (LMP) to end of pregnancy and their offspring compared to an unexposed reference group.

Study design: The C-VIPER is an international, noninterventional, post-marketing cohort study designed to collect prospective safety data among women vaccinated during pregnancy to prevent COVID-19.

Population: The study population includes 2 cohorts of pregnant women 18 years of age and older matched by country and gestational age (+/- 1 week):

• 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 before enrollment and had a negative screening test for the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) during pregnancy. These participants are enrolled through the International Coronavirus Exposure in Pregnancy (IRCEP) with the same methods as those in Cohort 1.

Registration and participation via website or mobile app 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 to one year of age 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, behaviors, reproductive history, chronic conditions, results of SARS-CoV-2 tests before and during this pregnancy, new COVID-19 vaccinations, use of medications, 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 IRCEP will be matched by country and gestational age at enrollment (+/- 1 week).

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. 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. Annual interim reports will be submitted to the Scientific Advisory Committee (SAC) for their review and feedback as well as abbreviated semiannual 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 that 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.

Sponsors: Pharmaceutical companies that hold marketing authorization of COVID-19 vaccines are invited to sponsor the C-VIPER. The C-VIPER will make an effort to enable Sponsors to meet regulatory requirements related to pregnancy exposure to COVID-19 vaccines.

Study Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 5000 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Target Follow-Up Duration: 21 Months
• Official Title: COVID-19 Vaccines International Pregnancy Exposure Registry (C-VIPER)
• Estimated Study Start Date: January 15, 2021
• Estimated Primary Completion Date: December 31, 2025
• Estimated Study Completion Date: December 31, 2025

Groups and Cohorts

Group/Cohort	Intervention/treatment
Vaccinated pregnant women; 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	Biological: COVID-19 vaccine; At least one dose of a COVID-19 vaccine.
Non-vaccinated pregnant women; Pregnant women unexposed to a COVID-19 vaccine before enrollment and had a negative screening test for the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) during pregnancy.

Outcome Measures

Primary Outcome Measures :

1. Obstetric outcomes [ Time Frame: 1 year ]
   Number of pregnant women vaccinated against COVID-19 and number of pregnant women not vaccinated against COVID-19 who experience abortion, antenatal bleeding, dysfunctional labor, gestational diabetes, hypertensive disorders of pregnancy, intrauterine growth retardation, maternal death, non-reassuring fetal status, pathways to premature birth, postpartum hemorrhage, or COVID-19.
2. Neonatal outcomes [ Time Frame: 1 year ]
   Number of newborns of women vaccinated against COVID-19 and number of newborns of women not vaccinated against COVID-19 during pregnancy who are diagnosed with congenital anomalies, failure to thrive, low birth weight, neonatal death, neonatal encephalopathy, neonatal infections, preterm birth, respiratory distress in the newborn, small for gestational age, stillbirth, or COVID-19.
3. Infant weight [ Time Frame: 1 year ]
   Change in weight from birth to 3, 6, 9, and 12 months of age among newborns of women vaccinated against COVID-19 during pregnancy and among newborns of women not vaccinated against COVID-19 during pregnancy.
4. Infant developmental milestones [ Time Frame: 1 year ]
   Change in developmental milestones from baseline at 6, 9, and 12 months based on the tool Caregiver Reported Early Development Instruments among the offspring of women vaccinated against COVID-19 during pregnancy and among offspring of women not vaccinated against COVID-19 during pregnancy.
5. Infant COVID-19 diagnosis [ Time Frame: 1 year ]
   Number of newborns of women vaccinated against COVID-19 during pregnancy and number of newborns of women not vaccinated against COVID-19 during pregnancy diagnosed with COVID-19 during the first year of life.
6. Infant height [ Time Frame: 1 year ]
   Change in height from birth to 3, 6, 9, and 12 months of age among newborns of women vaccinated against COVID-19 during pregnancy and among newborns of women not vaccinated against COVID-19 during pregnancy.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Persons assigned gender female at birth.
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

The target study population consists of pregnant women who are 18 years of age or 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 at the time of enrollment and had a negative screening test for SARS-CoV-2 during pregnancy. Both cohorts will be matched by country of residence and gestational age at enrollment (+/- 1 week).

Criteria

Inclusion Criteria:

• Pregnant women
• Aged 18 years or older
• Have received either:
• a COVID-19 vaccine from 30 days prior to the first day of the LMP to end of pregnancy or a negative screening test for SARS-CoV-2 during pregnancy
• Living in the countries where at least one COVID-19 vaccine is marketed
• Able and willing to sign the informed consent form agreeing to the conditions and requirements of the C-VIPER (exposed) or IRCEP extension (reference) using the studies website or mobile app.
• Willing to upload the minimum required data of the initial baseline questionnaire

Exclusion Criteria:

• <18 years of age

Contacts and Locations

Contacts

Contact: Diego Wyszynski, MD, MHS, PhD; 7472005468; hello@pregistry.com

Locations

United States, California

Pregistry

Los Angeles, California, United States, 90045

Sponsors and Collaborators

Pregistry

Harvard School of Public Health

Investigators

• Principal Investigator: Diego Wyszynski, MD, MHS, PhD; Pregistry

More Information

Additional Information:

COVID-19 Vaccines International Pregnancy Exposure Registry (C-VIPER) 

• Responsible Party: Pregistry
• ClinicalTrials.gov Identifier: NCT04705116
• Other Study ID Numbers: PR004
• First Posted: January 12, 2021
• Last Update Posted: January 13, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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.: Yes