Pregnancy and Infant Outcomes Following Exposure to PAXLOVID: A Post-Authorization Safety Study

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  PAXLOVID
• Study drug International non-proprietary name (INN) or common name:
  NIRMATRELVIR

  RITONAVIR
• Anatomical Therapeutic Chemical (ATC) code:
  (J05AE30) nirmatrelvir and ritonavir

  nirmatrelvir and ritonavir
• Medical condition to be studied:
  Abortion spontaneous

  Stillbirth

  Live birth

  Congenital anomaly

  Small for dates baby
• Additional medical condition(s):
  Induced termination of pregnancy, preterm birth

Population studied

• Short description of the study population:
  The base population for this study will include pregnancies among women that began (based on the estimated conception date [ECD], equal to the date of last menstrual period [LMP] + 14 days) between 01 March 2021 and 01 December 2025. For the assessment of infant outcomes, pregnancies that begin on or before 01 April 2025 will be eligible for inclusion. Additional qualifying and cohort criteria are outlined in the study protocol. ;
• Age groups:
  Adolescents (12 to < 18 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)
• Special population of interest:
  Pregnant women

Study design details

• Study design:
  This 5-year observational cohort study will use administrative healthcare claims data to assess PAXLOVID exposure and pregnancy and infant outcomes including SA, induced termination, stillbirth, livebirth, SGA, preterm birth, postnatal growth deficiency, and infant developmental delay and MCM.
• Main study objective:
  To estimate the risk of MCM among pregnant women exposed to PAXLOVID (and not other COVID-19 treatments) during pregnancy, pregnant women not exposed to PAXLOVID but exposed to other COVID-19 treatments, and pregnant women with COVID-19 not exposed to any COVID-19 treatments.
• Setting:
  The base population for this study will include pregnancies that began (based on ECD) between 01 March 2021 and 01 December 2025, among women treated for COVID-19 or with a COVID-19 diagnosis.
• Outcomes:
  Risk of MCM among pregnant women exposed to PAXLOVID only during pregnancy (Cohort 1), among pregnant women not exposed to PAXLOVID but exposed to other COVID-19 treatments (Cohort 2), and pregnant women with COVID-19 not exposed to any COVID-19 treatments (Cohort 3). Risk of spontaneous abortion, induced termination, stillbirth, live birth, preterm birth, and small for gestational age among the 3 study cohorts. Pending sufficient sample size, comparison of the risk of pregnancy and infant outcomes in Cohort 1 compared to, separately, Cohort 2 and Cohort 3.
• Data analysis plan:
  Descriptive summaries of baseline variables and prevalence of pregnancy and infant outcomes will be prepared for pregnancies in each cohort and exposure window. Adjudication results will be described including the number of medical records sought and retrieved. Pending sufficient sample size, comparative analyses will be undertaken for each of the pregnancy and infant outcomes, comparing the PAXLOVID-exposed pregnancy cohorts to the comparator pregnancy cohorts. Propensity scores will be developed and used to account for potential covariate imbalance between the study cohorts via inverse probability of treatment weighted (IPTW) regression. Sensitivity analyses will assess alternate exposure definitions and/or quantify the potential bias associated with unmeasured confounders or the occurrence of major congenital malformation leading to pregnancy loss.

Documents

Study, other information

C4671038_PROTOCOL_V1_02NOV2023.pdf