Paxlovid for Treatment of Long Covid

Phase 2

Completed

• Conditions: Post-acute Sequelae of SARS-CoV-2 Infection; Long COVID
• Interventions: Drug: Placebo; Drug: Nirmatrelvir; Drug: Ritonavir

• Registration Number: NCT05576662
• Lead Sponsor: Stanford University

Brief Summary

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."

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 Timeline

• Study First Submitted: 2022-10-10
• Study First Submitted QC: 2022-10-10
• Study First Posted: 2022-10-12
• Study Start: 2022-11-08
• Primary Completion: 2023-08-14
• Study Completion: 2023-09-12
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-06
• Last Update Posted: 2023-10-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 168

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo plus ritonavir	Placebo	Participants receive placebo to match nirmatrelvir plus ritonavir for 15 days, and attend follow-up visits through week 15.
Nirmatrelvir plus ritonavir	Ritonavir	Participants receive nirmatrelvir plus ritonavir (Paxlovid) for 15 days, and attend follow-up visits through week 15.
Nirmatrelvir plus ritonavir	Nirmatrelvir	Participants receive nirmatrelvir plus ritonavir (Paxlovid) for 15 days, and attend follow-up visits through week 15.
Placebo plus ritonavir	Ritonavir	Participants receive placebo to match nirmatrelvir plus ritonavir for 15 days, and attend follow-up visits through week 15.

Primary Outcome Measures

Name	Time	Method
Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score	Week 10	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).

Secondary Outcome Measures

Name	Time	Method
Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score	Day 15	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).
Number of Participants Reporting Relief of at Least One Core Symptom for 2 Weeks	Baseline through week 10, assessed at week 10	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.
Number of Participants With Overall Alleviation for 2 Weeks	Baseline through week 10, assessed at week 10	Overall alleviation defined as both: 1. Any core symptom(s) that are none/mild (Likert 0 or 1) at baseline are none at 10 weeks, and; 2. 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.
Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom	Assessed at weeks 5, 10, and 15	This outcome was to assess the severity of the most bothersome symptom experienced by participants. Each symptom was assessed on a 4-point Likert scale (range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms) using the Core Symptoms Severity Scale.
Time to Relief of the 6 Core Symptoms	Up to 15 weeks	Relief defined as reduction of severity from moderate to none, or severe to mild/none for 2 consecutive weeks (≥ 2-point Likert score change). Likert score range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms.
Time to Relief of the Most Bothersome Symptom	Up to 15 weeks	Relief defined as reduction of severity from moderate to none, or severe to mild/none for 2 consecutive weeks (≥ 2-point Likert score change). Likert score range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms.
Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function T-Score	Baseline and week 10	The PROMIS-Physical Function Short Form (SF) assesses difficulty level performing activities of daily living such as doing chores, climbing stairs, walking, and running errands. The assessment consists of 4 items (questions) with each item scored on 5-point Likert scale (higher scores correspond to better physical function). Scores are computed to a T-score metric, where 50 represents the mean for US general adult population and 10 is the standard deviation. A higher physical function T-score indicates better physical function.
Change in PROMIS Fatigue T-Score	Baseline and week 10	The PROMIS Fatigue Score assesses level of fatigue and its interference on daily activities. The assessment consists of 7 items (questions) with each item scored on 5-point Likert scale (higher scores correspond to more fatigue). Scores are computed to a T-score metric, where 50 represents the mean for US general adult population and 10 is the standard deviation. A higher fatigue T-score indicates greater fatigue.
Change in PROMIS Dyspnea-Severity T-Score	Baseline and week 10	The PROMIS-Fatigue Dyspnea-Severity Short Form assesses shortness of breath and its interference on daily activities. The assessment consists of 5 items (questions) scored on 4-point Likert scale with a 7-day recall period (higher scores correspond to worse symptoms). Scores are computed to a T-score metric, where 50 represents the mean for US general adult population and 10 is the standard deviation. A higher Dyspnea-Severity T-score indicates worse symptoms.
Change in PROMIS Cognitive Function Abilities T-Score	Baseline and week 10	The PROMIS-Cognitive Function Abilities Short Form assesses brain fog and its interference on daily activities. The assessment consists of 4 items scored on 5-point Likert scale with a 7-day recall period (higher scores indicate better cognitive function). Scores are computed to a T-score metric, where 50 represents the mean for US general adult population and 10 is the standard deviation. A higher Cognitive Function T-score indicates better cognitive function.
Change in Orthostatic Vitals Test	Baseline and week 10	This outcome measures the difference in supine to standing systolic blood pressure (SBP) and diastolic blood pressure (DBP).
Change in Heart Rate	Baseline and week 10	This outcome measures the difference in supine to standing heart rate.
Change in 1-minute Sit-to-stand Test	Baseline and week 10	Number of times participant is able to go from sitting (in an armless chair) to standing in 1 minute (sit to stand cycles).
Patient Global Impression of Severity (PGIS) Scale Score	Day 15, and weeks 5, 10, and 15	The PGIS reflects a participant's perception about the overall severity of their disease symptoms, rated from 1 to 6 (1 = not present; 2 = very mild; 3 = mild; 4 = moderate; 5 = severe; 6 = extremely severe).
Patient Global Impression of Change (PGIC) Scale Score	Day 15, and weeks 5, 10, and 15	The PGIC reflects a participant's perception about the overall efficacy of treatment and their overall status since the start of the treatment, 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).
Summative Severity Score for All Core Symptoms	Weeks 5, 10, and 15	Core Symptoms Severity Scale Scores for each of the 6 core symptoms were summed to create a summative score. Each core symptom is assessed on a 4-point Likert scale (range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms). Summative score range: 0 to 18 (high scores correspond to greater severity).
Percentage of Weeks 1-15 With Mild or no Symptoms	15 weeks	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).

Trial Locations

Locations (1)

Stanford University; 🇺🇸 Stanford, California, United States