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

Purpose

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.

Conditions

  • Long COVID-19
  • Long COVID

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
As part of screening, potential participants will answer symptom questions. Eligible participants will then complete relevant Symptom Cluster assessments at the Screening visit. Participants will subsequently be assigned to one of the three Symptom Clusters based on the assessments. Participants must meet certain criteria within a specific symptom cluster in order to be included in the cluster. After study enrollment and initial cluster assignment, further assessments will be performed. Participants will undergo assessments for the symptom clusters for which the participants qualify.
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)
Masking Description
Double-blind

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Paxlovid 25 day dosing 		Paxlovid (nirmatrelvir 300mg, ritonavir 100mg) bid x 25 days
  • Drug: Paxlovid 25 day dosing
    nirmatrelvir 300mg and ritonavir 100mg taken bid for 30 days
Experimental
Paxlovid 15 day dosing 		Paxlovid (nirmatrelvir 300mg, ritonavir 100mg) bid x 15 days then ritonavir 100mg plus nirmatrelvir-matching placebo x 10 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
Placebo Comparator
Control 		ritonavir 100mg plus nirmatrelvir-matching placebo bid x 25 days
  • Drug: Control
    ritonavir 100mg taken bid plus nirmatrelvir matching placebo bid for 30 days

Recruiting Locations

More Details

NCT ID
NCT05965726
Status
Active, not recruiting
Sponsor
Kanecia Obie Zimmerman

Detailed 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.