Paxlovid for Treatment of Long Covid (STOP-PASC)

Selective Trial Of Paxlovid for PASC (STOP-PASC): Randomized Double-Blind Placebo-Controlled Pilot Trial of Paxlovid for the Treatment of PASC

The purpose of this study is to compare whether being treated with Paxlovid (nirmatrelvir plus ritonavir) for 15 days works better than being treated with placebo (plus ritonavir) to reduce severe symptoms of Long Covid (the placebo does not have any active drug).

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."

Study Overview

• Status: Completed
• Conditions: Long COVID; Post-acute Sequelae of SARS-CoV-2 Infection
• Intervention / Treatment: Drug: Nirmatrelvir; Drug: Ritonavir; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nirmatrelvir plus ritonavir; Participants receive nirmatrelvir plus ritonavir (Paxlovid) for 15 days, and attend follow-up visits through week 15.	Drug: Nirmatrelvir; Two 150 mg tablets taken by mouth every 12 hours; Drug: Ritonavir; One 100 mg capsule taken by mouth every 12 hours
Placebo Comparator: Placebo plus ritonavir; Participants receive placebo to match nirmatrelvir plus ritonavir for 15 days, and attend follow-up visits through week 15.	Drug: Ritonavir; One 100 mg capsule taken by mouth every 12 hours; Drug: Placebo; Two tablets containing placebo matching nirmatrelvir taken by mouth every 12 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Core Symptoms Severity Scale Score	This measure will 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) is 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Core Symptoms Severity Scale Score	This measure will evaluate whether there is a difference between treatment with Paxlovid versus placebo on any of the 6 core symptoms of PASC at day 15 (adjusting for patients' baseline levels). Each symptom (fatigue, brain fog, dyspnea, body aches, gastrointestinal symptoms, cardiovascular symptoms) is assessed on a 4-point Likert scale (range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms).	Day 15
Number of participants reporting relief of at least one core symptom for 2 weeks	Relief defined as reduction of severity from moderate to none, or severe to mild/none (≥ 2-point Likert score change). Likert score range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms.	Baseline through week 10, assessed at week 10
Number of participants with overall alleviation for 2 weeks	Overall alleviation defined as both: Any core symptom(s) that are none/mild (Likert 0 or 1) at baseline are none at 10 weeks, and; Any core symptom(s) that are moderate/severe (Likert 2 or 3) at baseline are none/mild at 10 weeks. Likert score range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms.	Baseline through week 10, assessed at week 10
Severity of the most bothersome symptom	Severity assessed on a 4-point Likert scale (range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms).	Assessed at weeks 5, 10, and 15
Time to relief of the 6 core symptoms	Relief defined as reduction of severity from moderate to none, or severe to mild/none (≥ 2-point Likert score change). Likert score range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms.	Up to 15 weeks
Change in PROMIS Physical Function Score	The PROMIS-Physical Function Short Form assesses difficulty level performing activities of daily living such as doing chores, climbing stairs, walking, and running errands.	Baseline and week 10
Change in PROMIS Fatigue Score	The PROMIS Fatigue Score assesses level of fatigue and its interference on daily activities.	Baseline and week 10
Change in PROMIS Dyspnea-Severity Score	The PROMIS-Fatigue Dyspnea-Severity Short Form assesses shortness of breath and its interference on daily activities.	Baseline and week 10
Change in PROMIS Cognitive Function Abilities Score	The PROMIS-Cognitive Function Abilities Short Form assesses brain fog and its interference on daily activities.	Baseline and week 10
Change in orthostatic vitals test	This outcome measures the difference in seated versus standing blood pressure.	Baseline and week 10
Change in 1-minute sit-to-stand test	Number of times participant is able to go from sitting (in an armless chair) to standing in 1 minute.	Baseline and week 10
Patient Global Impression of Severity (PGIS) scale score	Change in health status rated from 1 to 6. 1 = not present; 2 = very mild; 3 = mild; 4 = moderate; 5 = severe; 6 = extremely severe.	Weeks 5, 10, and 15
Patient Global Impression of Change (PGIC) scale score	Change in health status rated from 1 to 7. 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse.	Baseline and weeks 5, 10, and 15

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Pfizer
• Investigators: Principal Investigator: Upinder Singh, MD, Stanford University; Principal Investigator: Linda Geng, MD, PhD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2022
• Primary Completion (Actual): August 14, 2023
• Study Completion (Actual): September 12, 2023

Study Registration Dates

• First Submitted: October 10, 2022
• First Submitted That Met QC Criteria: October 10, 2022
• First Posted (Actual): October 12, 2022

Study Record Updates

• Last Update Posted (Estimated): October 10, 2023
• Last Update Submitted That Met QC Criteria: October 6, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Chronic Disease; Post-Infectious Disorders; COVID-19; Post-Acute COVID-19 Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Nirmatrelvir
• Other Study ID Numbers: 66994

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Currently, there is no plan for data sharing.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No