Paxlovid for Treatment of Long Covid (STOP-PASC)

• ClinicalTrials.gov Identifier: NCT05576662
• Recruitment Status: Completed
• First Posted: October 12, 2022
• Last Update Posted: October 10, 2023
• Sponsor: Stanford University
• Collaborator: Pfizer
• Information provided by (Responsible Party): Stanford University

Tracking Information

• First Submitted Date: October 10, 2022
• First Posted Date: October 12, 2022
• Last Update Posted Date: October 10, 2023
• Actual Study Start Date: November 8, 2022
• Actual Primary Completion Date: August 14, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 1, 2022)

Core Symptoms Severity Scale Score [ Time Frame: Week 10 ]

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).

Original Primary Outcome Measures (submitted: October 10, 2022)

Change in PROMIS Fatigue Score [ Time Frame: Baseline and week 10 ]

PROMIS-Fatigue Short Form (SF 7a v1.0) is a 7-item scale developed by the Patient-Reported Outcome Measurement Information System (PROMIS). Respondents indicate how much they agree with fatigue item statements on a scale from 1 (not at all) to 5 (very much). Total scores are summed for a total score range from 7 to 35 with higher scores indicating greater fatigue.

Current Secondary Outcome Measures (submitted: December 12, 2022)

• Core Symptoms Severity Scale Score [ Time Frame: Day 15 ]
  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).
• Number of participants reporting relief of at least one core symptom for 2 weeks [ Time Frame: 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 [ Time Frame: 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.
• Severity of the most bothersome symptom [ Time Frame: Assessed at weeks 5, 10, and 15 ]
  Severity assessed on a 4-point Likert scale (range: 0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms).
• Time to relief of the 6 core symptoms [ Time Frame: Up to 15 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.
• Change in PROMIS Physical Function Score [ Time Frame: Baseline and week 10 ]
  The PROMIS-Physical Function Short Form assesses difficulty level performing activities of daily living such as doing chores, climbing stairs, walking, and running errands.
• Change in PROMIS Fatigue Score [ Time Frame: Baseline and week 10 ]
  The PROMIS Fatigue Score assesses level of fatigue and its interference on daily activities.
• Change in PROMIS Dyspnea-Severity Score [ Time Frame: Baseline and week 10 ]
  The PROMIS-Fatigue Dyspnea-Severity Short Form assesses shortness of breath and its interference on daily activities.
• Change in PROMIS Cognitive Function Abilities Score [ Time Frame: Baseline and week 10 ]
  The PROMIS-Cognitive Function Abilities Short Form assesses brain fog and its interference on daily activities.
• Change in orthostatic vitals test [ Time Frame: Baseline and week 10 ]
  This outcome measures the difference in seated versus standing blood pressure.
• Change in 1-minute sit-to-stand test [ Time Frame: Baseline and week 10 ]
  Number of times participant is able to go from sitting (in an armless chair) to standing in 1 minute.
• Patient Global Impression of Severity (PGIS) scale score [ Time Frame: Weeks 5, 10, and 15 ]
  Change in health status 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 [ Time Frame: Baseline and weeks 5, 10, and 15 ]
  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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Paxlovid for Treatment of Long Covid
• Official Title: Selective Trial Of Paxlovid for PASC (STOP-PASC): Randomized Double-Blind Placebo-Controlled Pilot Trial of Paxlovid for the Treatment of PASC

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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: Nirmatrelvir
  Two 150 mg tablets taken by mouth every 12 hours
• Drug: Placebo
  Two tablets containing placebo matching nirmatrelvir taken by mouth every 12 hours
• Drug: Ritonavir
  One 100 mg capsule taken by mouth every 12 hours

Study Arms

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

  • Drug: Nirmatrelvir
  • Drug: Ritonavir
• Placebo Comparator: Placebo plus ritonavir
  Participants receive placebo to match nirmatrelvir plus ritonavir for 15 days, and attend follow-up visits through week 15.
  Interventions:

  • Drug: Placebo
  • Drug: Ritonavir

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 29, 2023): 168
• Original Estimated Enrollment (submitted: October 10, 2022): 200
• Actual Study Completion Date: September 12, 2023
• Actual Primary Completion Date: August 14, 2023 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05576662
• Other Study ID Numbers: 66994
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Currently, there is no plan for data sharing.

• Current Responsible Party: Stanford University
• Original Responsible Party: Same as current
• Current Study Sponsor: Stanford University
• Original Study Sponsor: Same as current
• Collaborators: Pfizer

Investigators

• Principal Investigator: Upinder Singh, MD; Stanford University
• Principal Investigator: Linda Geng, MD, PhD; Stanford University

• PRS Account: Stanford University
• Verification Date: October 2023