Paxlovid is an antiviral used for treating COVID-19 in adults who do not require supplemental oxygen and who are at increased risk of the disease becoming severe. The safety of Paxlovid in pregnant women is unknown.
This study aims to explore the safety of Paxlovid when used in pregnancy. The primary objective is to estimate the proportion of several adverse outcomes in pregnant women with COVID-19 who are treated with Paxlovid, and to estimate the risk for these outcomes in pregnant women treated with Paxlovid compared to the risk in pregnant women with COVID-19 who use the antiviral molnupiravir (or comparable antivirals) or who are untreated. The outcomes are miscarriage, induced abortion, death of the fetus, early delivery, birth defects, poor growth of the fetus, diabetes during pregnancy, hypertension during pregnancy, haemorrhage after giving birth, and maternal death. The secondary objective is to assess other maternal outcomes based on diseases observed among pregnant women who used Paxlovid.
The study will use existing data from CPRD in the UK, as well as data from France and Spain. Analyses will follow a common study protocol and statistical analysis plan. Results from each data source will be combined using statistical techniques. The findings of this study will inform about the safety of Paxlovid in pregnant women.
This study is a commitment to the European Medicines Agency and the UK Medicines and Healthcare products Regulatory Agency and is registered in a repository for regulatory and other studies (EU PAS Register reference number: EUPAS50117).
Paxlovid is an antiviral used to treat COVID-19 in adults who do not require supplemental oxygen and who are at increased risk of progression to severe COVID-19. The safety of Paxlovid in pregnant women is unknown.
The primary objective is to estimate the prevalence, prevalence ratio, and prevalence difference of several adverse outcomes in women with COVID-19 who are exposed to Paxlovid during pregnancy, compared with those in women with COVID-19 who are exposed to molnupiravir (or other comparable medications for COVID-19) during pregnancy, or to women with COVID-19 unexposed to any study medications during pregnancy. The prespecified study outcomes are spontaneous abortion, elective termination, stillbirth, preterm delivery, major congenital malformations, intrauterine growth retardation/small for gestational age, gestational diabetes, gestational hypertension, postpartum haemorrhage, and maternal death. The secondary objective is to assess additional maternal outcomes to be identified based on conditions appearing in the study population after exposure to Paxlovid (exploratory outcomes).
Molnupiravir, an antiviral with a similar recommended usage, will be the active comparator, where available; other drugs may be incorporated as active comparators as more information becomes available. The second comparator group is women with COVID-19 unexposed to any study medication during pregnancy.
The study will use existing data from the UK (CPRD), France and Spain translated into the ConcePTION common data model. Analyses will follow a common protocol and statistical analysis plan, and will use centralized programming. Analyses will include descriptive and comparative components, including propensity score models, and bootstrapping to calculate the confidence intervals. Data-source-specific results will be combined via meta-analysis.
This study is a commitment to the European Medicines Agency and the UK Medicines and Healthcare products Regulatory Agency. This protocol is registered in the EU PAS Register (EUPAS50117).
This is the second out of two data extractions for this study.
Prespecified study outcomes: Spontaneous abortion; Elective termination; Stillbirth; Preterm delivery (all, iatrogenic, and spontaneous); Major congenital malformations; Intrauterine growth retardation/small for gestational age; Gestational diabetes; Gestational hypertension; Postpartum haemorrhage; Maternal death.
Exploratory outcomes: empirically identified outcomes identified from diagnosis codes from outpatient diagnoses, hospitalisation discharge diagnoses and emergency department diagnoses recorded up to 1 month after the Paxlovid dispensing date among eligible Paxlovid-exposed individuals.
Andrea Margulis - Chief Investigator - RTI Health Solutions ( USA )
Nuria Saigi - Corresponding Applicant - RTI Health Solutions ( USA )
Anne-Elie Carsin - Collaborator - RTI Health Solutions ( USA )
Becky MacKay - Collaborator - RTI Health Solutions ( USA )
CRISTINA REBORDOSA GARCIA - Collaborator - RTI Health Solutions ( USA )
David Martinez - Collaborator - RTI Health Solutions ( USA )
Estel Plana Hortoneda - Collaborator - RTI Health Solutions ( USA )
Jaume Aguado - Collaborator - RTI Health Solutions ( USA )
JOSEP RAMON MARSAL MORA - Collaborator - RTI Health Solutions ( USA )
Katica Boric - Collaborator - RTI Health Solutions ( USA )
Maria Foraster Pulido - Collaborator - RTI Health Solutions ( USA )
Raquel Garcia Esteban - Collaborator - RTI Health Solutions ( USA )
Sandra Bertran - Collaborator - RTI Health Solutions ( USA )
Susana Perez-Gutthann - Collaborator - RTI Health Solutions ( USA )
Xabier Garcia de Albeniz - Collaborator - RTI Health Solutions ( USA )
Nuria Saigi - Collaborator - RTI Health Solutions ( USA )
HES Admitted Patient Care;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation;CPRD Aurum Ethnicity Record;CPRD Aurum Mother-Baby Link;CPRD Aurum Pregnancy Register