Clinical trial NCT05576662: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Post-acute Sequelae of SARS-CoV-2 Infection
Long COVID
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2022-10-12
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With No, Mild, Moderate, or Severe Symptoms at Week 10 According to the Core Symptoms Severity Scale Score
timeFrame: Week 10
Secondary outcomes:
measure: Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 According to the Core Symptoms Severity Scale Score
timeFrame: Day 15
measure: Number of Participants Reporting Relief of at Least One Core Symptom for 2 Weeks
timeFrame: Baseline through week 10, assessed at week 10
measure: Number of Participants With Overall Alleviation for 2 Weeks
timeFrame: Baseline through week 10, assessed at week 10
measure: Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom
timeFrame: Assessed at weeks 5, 10, and 15
measure: Time to Relief of the 6 Core Symptoms
timeFrame: Up to 15 weeks
measure: Time to Relief of the Most Bothersome Symptom
timeFrame: Up to 15 weeks
measure: Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function T-Score
timeFrame: Baseline and week 10
measure: Change in PROMIS Fatigue T-Score
timeFrame: Baseline and week 10
measure: Change in PROMIS Dyspnea-Severity T-Score
timeFrame: Baseline and week 10
measure: Change in PROMIS Cognitive Function Abilities T-Score
timeFrame: Baseline and week 10
measure: Change in Orthostatic Vitals Test
timeFrame: Baseline and week 10
measure: Change in Heart Rate
timeFrame: Baseline and week 10
measure: Change in 1-minute Sit-to-stand Test
timeFrame: Baseline and week 10
measure: Patient Global Impression of Severity (PGIS) Scale Score
timeFrame: Day 15, and weeks 5, 10, and 15
measure: Patient Global Impression of Change (PGIC) Scale Score
timeFrame: Day 15, and weeks 5, 10, and 15
measure: Summative Severity Score for All Core Symptoms
timeFrame: Weeks 5, 10, and 15
measure: Percentage of Weeks 1-15 With Mild or no Symptoms
timeFrame: 15 weeks
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University
name: Upinder Singh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Linda Geng, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.