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."
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
168
Two 150 mg tablets taken by mouth every 12 hours
Two tablets containing placebo matching nirmatrelvir taken by mouth every 12 hours
One 100 mg capsule taken by mouth every 12 hours
Stanford University
Stanford, California, United States
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).
Time frame: Week 10
Number of Participants With No, Mild, Moderate, or Severe Symptoms at Day 15 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).
Time frame: 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.
Time frame: Baseline through week 10, assessed at week 10
Number of Participants With Overall Alleviation for 2 Weeks
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.
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Time frame: Baseline through week 10, assessed at week 10
Number of Participants With No, Mild, Moderate, or Severe Symptoms of Their Most Bothersome Symptom
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 frame: 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 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 frame: Up to 15 weeks
Time to Relief of the Most Bothersome Symptom
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 frame: Up to 15 weeks
Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function T-Score
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.
Time frame: Baseline and week 10
Change in PROMIS Fatigue T-Score
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.
Time frame: Baseline and week 10
Change in PROMIS Dyspnea-Severity T-Score
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.
Time frame: Baseline and week 10
Change in PROMIS Cognitive Function Abilities T-Score
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.
Time frame: Baseline and week 10
Change in Orthostatic Vitals Test
This outcome measures the difference in supine to standing systolic blood pressure (SBP) and diastolic blood pressure (DBP).
Time frame: Baseline and week 10
Change in Heart Rate
This outcome measures the difference in supine to standing heart rate.
Time frame: 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 (sit to stand cycles).
Time frame: Baseline and week 10
Patient Global Impression of Severity (PGIS) Scale Score
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).
Time frame: Day 15, and weeks 5, 10, and 15
Patient Global Impression of Change (PGIC) Scale Score
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).
Time frame: Day 15, and weeks 5, 10, and 15
Summative Severity Score for All Core Symptoms
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).
Time frame: Weeks 5, 10, and 15
Percentage of Weeks 1-15 With Mild or no Symptoms
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).
Time frame: 15 weeks