Paxlovid for Treatment of Long Covid

NCT ID: NCT05576662

Last Updated: 2025-09-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 168 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-08
• Study Completion Date: 2023-09-12

Brief Summary

The purpose of this study is to compare whether being treated with nirmatrelvir plus ritonavir for 15 days works better than being treated with placebo plus ritonavir to reduce severe symptoms of Long Covid.

Participants will have 5 planned visits to the study clinic over 15 weeks and will take the drug (or placebo) for the first 15 days.

This study uses the term post-acute sequelae of SARS-CoV-2 (PASC), which is another name for "Long Covid."

Detailed Description

An exploratory sub-study will investigate the correlation of physical activity and biometric parameters from digital wearable devices with the subjective symptom severity and other patient-reported outcomes in the main study. All participants with iPhone 6S Plus or newer will be offered an opportunity to opt-in to this sub-study. An Apple Watch and Bluetooth-enabled blood pressure monitor will be provided to participants and data will be collected for the duration of the main study to track participants' physiological and behavioral trends in the Paxlovid versus placebo groups.

Conditions

Post-acute Sequelae of SARS-CoV-2 Infection; Long COVID

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Nirmatrelvir plus ritonavir

Participants receive nirmatrelvir plus ritonavir (Paxlovid) for 15 days, and attend follow-up visits through week 15.

Group Type: EXPERIMENTAL

Nirmatrelvir

Intervention Type: DRUG

Two 150 mg tablets taken by mouth every 12 hours

Ritonavir

Intervention Type: DRUG

One 100 mg capsule taken by mouth every 12 hours

Placebo plus ritonavir

Participants receive placebo to match nirmatrelvir plus ritonavir for 15 days, and attend follow-up visits through week 15.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Two tablets containing placebo matching nirmatrelvir taken by mouth every 12 hours

Ritonavir

Intervention Type: DRUG

One 100 mg capsule taken by mouth every 12 hours

Interventions

Nirmatrelvir

Two 150 mg tablets taken by mouth every 12 hours

Intervention Type: DRUG

Placebo

Two tablets containing placebo matching nirmatrelvir taken by mouth every 12 hours

Intervention Type: DRUG

Ritonavir

One 100 mg capsule taken by mouth every 12 hours

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Normal or near-normal kidney function
• History of confirmed COVID-19 infection that preceded the post-COVID symptoms
• Post-COVID-19 symptoms persisting greater than three months
• At least 2 post-COVID symptoms of moderate or severe intensity (fatigue, brain fog, shortness of breath, body aches, gastrointestinal symptoms, or cardiovascular symptoms)
• Willing to report all vaccinations
• Women of childbearing potential or men whose partners may become pregnant must use acceptable method of contraception during the treatment period and for 28 days after the last dose of the study drug
• Willing and able to adhere to study procedures and available for the duration of the study

Exclusion Criteria

• Suspected or confirmed pregnancy or breastfeeding
• Severe liver disease
• Prior use of study drug or other COVID treatment within 30 days
• Hypersensitivity or other contraindication to any components of the study drug
• Current or expected use of any medication dependent on or inducer of CYP3A4
• Current or expected use of supplements or herbs (unless medically necessary) that cannot be temporarily held (period as determined necessary by investigators)
• HIV infection with viral load >50 copies/ml
• Suspected or confirmed active COVID infection within 30 days
• History of COVID vaccine within 28 days prior to enrollment, or other vaccine (influenza, shingles, etc.) within 14 days of enrollment, or planned use of any vaccine until the primary endpoint has been met (10 weeks)
• Other medical condition(s) or concomitant therapy that would compromise participant's safety or compliance with the study protocol or significantly confound interpretation of study results, as determined by study investigators
• Current enrollment in, or discontinuation within the last 30 days from, a clinical trial involving any investigational drug or device
• Inability to provide informed consent
• Currently hospitalized

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Upinder Singh, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Linda Geng, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University

Stanford, California, United States

Countries

United States

References

Geng LN, Bonilla H, Hedlin H, Jacobson KB, Tian L, Jagannathan P, Yang PC, Subramanian AK, Liang JW, Shen S, Deng Y, Shaw BJ, Botzheim B, Desai M, Pathak D, Jazayeri Y, Thai D, O'Donnell A, Mohaptra S, Leang Z, Reynolds GZM, Brooks EF, Bhatt AS, Shafer RW, Miglis MG, Quach T, Tiwari A, Banerjee A, Lopez RN, De Jesus M, Charnas LR, Utz PJ, Singh U. Nirmatrelvir-Ritonavir and Symptoms in Adults With Postacute Sequelae of SARS-CoV-2 Infection: The STOP-PASC Randomized Clinical Trial. JAMA Intern Med. 2024 Sep 1;184(9):1024-1034. doi: 10.1001/jamainternmed.2024.2007.

Reference Type: RESULT

PMID: 38848477 (View on PubMed)

Gunturkun F, Hedlin H, Botzheim B, Deng Y, Bonilla H, Jagannathan P, Quach TC, Kim S, Lin M, O'Riordan G, Tzeng H, Adamowicz L, Demanuele C, Cai X, Yang PC, Singh U, Geng LN. Digital Biometric Measures in Long COVID: A Secondary Analysis of the STOP-PASC Randomized Clinical Trial. JAMA Netw Open. 2025 Aug 1;8(8):e2526901. doi: 10.1001/jamanetworkopen.2025.26901.

Reference Type: RESULT

PMID: 40810942 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

66994

Identifier Type: -

Identifier Source: org_study_id