This is an appendix of master protocol (NCT05595369) designed to be flexible so that itis suitable for a wide range of settings within health care systems and in communitysettings where it can be integrated into COVID-19 programs and subsequent treatmentplans. This sub-study is a prospective, multi-center, double-blind, randomized,controlled trial evaluating nirmatrelvir/ritonavir (Paxlovid) in two dosing durations forthe treatment of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). The study isevaluating potential mechanisms of action, efficacy, and safety of antivirals and othertherapeutics in individuals with PASC, according to the platform protocol objectives. Thehypothesis is that persistent viral infection and/or overactive/chronic immune responseand inflammation are underlying contributors to PASC and that antiviral and otherapplicable therapies may result in viral clearance or decreased inflammation andimprovement in PASC symptoms.
For this appendix of the master protocol (NCT05595369), participants will be randomized
to Paxlovid (nirmatrelvir/ritonavir) vs. ritonavir control plus nirmatrelvir-matching
placebo.
When there are multiple study interventions (sub-studies) available under the master
protocol (NCT05595369), randomization will occur based on the specific
inclusion/exclusion criteria of each appendix.
Drug: Paxlovid 25 day dosing
nirmatrelvir 300mg and ritonavir 100mg taken bid for 30 days
Drug: Paxlovid 15 day dosing
nirmatrelvir 300mg and ritonavir 100mg taken bid for 15 days then ritonavir 100mg taken
bid plus nirmatrelvir matching placebo bid for 15 days
Drug: Control
ritonavir 100mg taken bid plus nirmatrelvir matching placebo bid for 30 days
See NCT NCT05595369 for RECOVER-VITAL: Platform Protocol level exclusion criteria which
applies to this appendix
Additional Appendix Level Exclusion Criteria:
1. Known pregnancy*
2. Active or expected breastfeeding during the study
3. Known eGFR < 30 mL/min
4. Known severe hepatic impairment (Child-Pugh Class C)
5. Current use of drugs highly dependent on CYP3A for clearance** and for which
elevated concentrations are associated with serious and/or life-threatening
reactions and which cannot be interrupted during the time of study administration
and within seven days before and after study drug administration
6. Current use of potent CYP3A inducers** where significantly reduced nirmatrelvir or
ritonavir plasma concentrations may be associated with the potential for loss of
virologic response and possible resistance
- A pregnancy test must be performed at the Baseline Visit for participants who
are capable of becoming pregnant.
- A guide of drugs that may be contraindicated are listed in Section 4
CONTRAINDICATIONS of the Full Prescribing Information of the EUA for
PAXLOVID.
https://labeling.pfizer.com/ShowLabeling.aspx?id=16474&format=pdf
All sites listed under NCT05595369
Durham, North Carolina, United States
Not Provided