Paxlovid for Treatment of Long Covid

NCT05576662 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 66994
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 1

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."

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score

  This measure was to evaluate whether there is a difference between treatment with Paxlovid versus placebo on any of the 6 core symptoms of PASC at week 10 (adjusting for patients' baseline levels). Each symptom (fatigue, brain fog, dyspnea, body aches, gastrointestinal symptoms, cardiovascular symptoms) was assessed on a 4-point Likert scale (range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms).

  Week 10

Secondary Outcomes (17)

• Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score

  Day 15

• Number of Participants Reporting Relief of at Least One Core Symptom for 2 Weeks

  Baseline through week 10, assessed at week 10

• Number of Participants With Overall Alleviation for 2 Weeks

  Baseline through week 10, assessed at week 10

• Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom

  Assessed at weeks 5, 10, and 15

• Time to Relief of the 6 Core Symptoms

  Up to 15 weeks

Study Arms (2)

Nirmatrelvir plus ritonavir

EXPERIMENTAL

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

Drug: Nirmatrelvir; Drug: Ritonavir

Placebo plus ritonavir

PLACEBO COMPARATOR

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

Drug: Placebo; Drug: Ritonavir

Interventions

Nirmatrelvir DRUG

Two 150 mg tablets taken by mouth every 12 hours

Nirmatrelvir plus ritonavir

Placebo DRUG

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

Placebo plus ritonavir

Ritonavir DRUG

One 100 mg capsule taken by mouth every 12 hours

Nirmatrelvir plus ritonavir; Placebo plus ritonavir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead
• Pfizer: collaborator

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

Related Publications (2)

• 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.

  PMID: 38848477 RESULT

• 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.

  PMID: 40810942 RESULT

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome

Interventions

nirmatrelvir; Ritonavir

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Linda N. Geng, MD, PhD
• Organization: Stanford University

geng@stanford.edu

650-723-4000

Study Officials

• Upinder Singh, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Linda Geng, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2022
• First Posted: October 12, 2022
• Study Start: November 8, 2022
• Primary Completion: August 14, 2023
• Study Completion: September 12, 2023
• Last Updated: September 4, 2025
• Results First Posted: September 25, 2024

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)