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 COVID-19 disease becoming severe. The safety of Paxlovid in patients with moderate or severe kidney or liver damage is unknown.
This study aims to explore the safety of Paxlovid in patients with COVID-19 and moderate or severe liver or kidney damage. For both populations, the primary objectives are to assess the safety of Paxlovid compared to two comparator groups; and to assess side effects resulting from drug overexposure due to impaired liver/kidney function and regarding severity and frequency compared with the comparator groups. The comparator groups are the population prescribed molnupiravir (or comparable COVID-19 antivirals), and the patients with COVID-19 who had not received Paxlovid, molnupiravir or other comparable antivirals. The secondary objective is to assess all safety events included in the primary objective that require hospitalisation or emergency department visits.
The study will use existing data from the UK (CPRD), 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 patients with COVID-19 and moderate/severe kidney or liver damage.
This study is a commitment to the European Medicines Agency and is registered in a repository for regulatory and other studies (EU PAS Register reference number: EUPAS50123).
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 patients with moderate or severe kidney or liver damage is unknown.
The research questions are: what is the safety profile of Paxlovid in patients with COVID-19 and moderate or severe hepatic impairment, and what is the safety profile of Paxlovid in patients with COVID-19 and moderate or severe renal impairment? For both populations, the primary objectives are to assess the safety of Paxlovid compared to patients prescribed molnupiravir (or other comparable COVID-19 medications, where available), and to unexposed patients with COVID-19. The primary outcomes are any safety events and events of special interest (severe vomiting, nausea, diarrhoea, or abdominal pain; headache, dysgeusia, hypertension, and anaphylactic reactions for both populations, and hepatic transaminase elevations, clinical hepatitis, and jaundice for the hepatic impairment population). The secondary objective is to assess all safety events included in the primary objective that require hospitalisation or emergency department visits. The study will employ a cohort design and use existing data sources in the UK (CPRD), France and Spain. The feasibility component will provide counts and characteristics of the target population.
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. This protocol is registered in the EU PAS Register (EUPAS50117).
This is the first out of two data extractions for this study.
Primary outcomes:
Any safety event in the hepatic impairment population; Hepatic transaminase elevations, clinical hepatitis, or jaundice as safety outcomes of special interest in the hepatic impairment population; Severe vomiting, nausea, diarrhoea, or abdominal pain as safety outcomes of special interest in the hepatic impairment population; Dysgeusia as safety outcome of special interest in the hepatic impairment population; Headache as safety outcome of special interest in the hepatic impairment population; Hypertension as safety outcome of special interest in the hepatic impairment population; Anaphylactic reactions as safety outcome of special interest in the hepatic impairment population.
Any safety event in the renal impairment population; Severe vomiting, nausea, diarrhoea, or abdominal pain as safety outcomes of special interest in the renal impairment population; Dysgeusia as safety outcome of special interest in the renal impairment population; Headache as safety outcome of special interest in the renal impairment population; Hypertension as safety outcome of special interest in the renal impairment population; Anaphylactic reactions as safety outcome of special interest in the renal impairment population.
Secondary outcomes:
Hepatic transaminase elevations, clinical hepatitis, or jaundice resulting in hospitalization or emergency department visits in the hepatic impairment population; Severe vomiting, nausea, diarrhoea, or abdominal pain resulting in hospitalization or emergency department visits in the hepatic impairment population; Dysgeusia resulting in hospitalization or emergency department visits in the hepatic impairment population; Headache resulting in hospitalization or emergency department visits in the hepatic impairment population; Hypertension resulting in hospitalization or emergency department visits in the hepatic impairment population; Anaphylactic reactions resulting in hospitalization or emergency department visits in the hepatic impairment population.
Severe vomiting, nausea, diarrhoea, or abdominal pain resulting in hospitalization or emergency department visits in the renal impairment population; Dysgeusia resulting in hospitalization or emergency department visits in the renal impairment population; Headache resulting in hospitalization or emergency department visits in the renal impairment population; Hypertension resulting in hospitalization or emergency department visits in the renal impairment population; Anaphylactic reactions resulting in hospitalization or emergency department visits in the renal impairment population.
CRISTINA REBORDOSA GARCIA - Chief Investigator - RTI Health Solutions ( USA )
Becky MacKay - Corresponding Applicant - RTI Health Solutions ( USA )
Andrea Margulis - Collaborator - RTI Health Solutions ( USA )
Anne-Elie Carsin - 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 )
Nuria Saigi - 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 )
HES Admitted Patient Care;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation;CPRD Aurum Ethnicity Record