RECOVER-VITAL: Platform Protocol, Appendix to Measure the Effects of Paxlovid on Long COVID Symptoms

Kanecia Obie Zimmerman

Status and phase: Completed; Phase 2

Conditions: Long COVID; Long COVID-19

Treatments: Drug: Paxlovid 25 day dosing; Drug: Paxlovid 15 day dosing; Drug: Ritonavir plus nirmatrelvir-matching placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05965726

OTA-21-015G (Other Grant/Funding Number)

Pro00111697_A

Details and patient eligibility

About

This is an appendix of master protocol (NCT05595369) designed to be flexible so that it is suitable for a wide range of settings within health care systems and in community settings where it can be integrated into COVID-19 programs and subsequent treatment plans. This sub-study is a prospective, multi-center, double-blind, randomized, controlled trial evaluating nirmatrelvir/ritonavir (Paxlovid) in two dosing durations for the treatment of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). The study is evaluating potential mechanisms of action, efficacy, and safety of antivirals and other therapeutics in individuals with PASC, according to the platform protocol objectives. The hypothesis is that persistent viral infection and/or overactive/chronic immune response and inflammation are underlying contributors to PASC and that antiviral and other applicable therapies may result in viral clearance or decreased inflammation and improvement in PASC symptoms.

Full description

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.

Enrollment: 964 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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964 participants in 3 patient groups, including a placebo group

Paxlovid 25 day dosing

Experimental group

Description:

Paxlovid (nirmatrelvir 300mg, ritonavir 100mg) BID (twice a day) x 25 days

Treatment:

Drug: Paxlovid 25 day dosing

Paxlovid 15 day dosing

Experimental group

Description:

Paxlovid (nirmatrelvir 300mg, ritonavir 100mg) BID (twice a day) x 15 days then ritonavir 100mg plus nirmatrelvir-matching placebo x 10 days

Treatment:

Drug: Paxlovid 15 day dosing

Ritonavir plus nirmatrelvir-matching placebo

Placebo Comparator group

Description:

Ritonavir 100mg plus nirmatrelvir-matching placebo BID (twice a day) x 25 days

Treatment:

Drug: Ritonavir plus nirmatrelvir-matching placebo