Trial Outcomes & Findings for RECOVER-VITAL: Platform Protocol, Appendix to Measure the Effects of Paxlovid on Long COVID Symptoms (NCT NCT05965726)

Study recruitment period was from late July 2023 to mid-August 2024 at 69 US sites. Recruiting centers were a mix of large academic and small independent research sites in rural and urban, outpatient settings.

RECOVER-VITAL: Platform Protocol, Appendix to Measure the Effects of Paxlovid on Long COVID Symptoms

PROMIS Cognitive 8a is a questionnaire assessing self-reported cognitive impairments over the past 7 days using 8 items. It assesses the frequency that respondents experienced cognitive impairments on a scale ranging from 5 (never) to 1 (very often; several times a day). The total raw score is transformed into a T-score, with higher scores representing better cognitive function. The T-scores are interpreted in relation to a US reference population and are scaled to have mean = 50 and SD = 10 in the reference population. The primary endpoint for the cognitive dysfunction symptom cluster is improvement of at least 5 T-score points on the PROMIS-cognitive 8a as measured at Day 90 compared to baseline.

The Orthostatic Hypotension Questionnaire (OHQ) is a patient reported outcome designed to assess the severity and impact of orthostatic hypotension (OH), a condition characterized by a sudden drop in blood pressure when standing. The OHQ consists of two main components: the Orthostatic Hypotension Symptom Assessment (OHSA) and the Orthostatic Hypotension Daily Activity Scale (OHDAS). The OHSA consists of 6 items measuring severity on a scale ranging from 0 (none) to 10 (worst possible). The OHDAS assesses the extent to which OH interferes with daily life on a scale ranging from 0 (no interference) to 10 (total interference). The primary endpoint for the autonomic dysfunction symptom cluster is improvement as defined by at least a 1-point decrease in the response to OHQ question 1 at Day 90 compared to baseline.

The Modified Depaul Symptom Questionnaire-Post Exertional Malaise (DSQ-PEM) is a patient-reported outcome designed to assess the frequency and severity of symptoms worsening after physical or mental exertion. The first 10 items of DSQ-PEM assess frequency and severity of the following 5 exercise-related impairments. These items were modified for the current study to use a 7-day instead of 6-month look back period. Frequency is rated on a 5-point Likert scale: 0 = none of the time, 1 = a little of the time, 2 = about half the time, 3 = most of the time, and 4 = all of the time. Severity is also rated on a 5-point Likert scale: 0 = symptom not present, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. The primary endpoint for the exercise symptom cluster is improvement in PEM, defined as having no symptoms of moderate or greater severity with 50% or more frequency as determined by the DSQ-PEM short form at Day 90.

The Neurocognitive battery is a performance measure used to assess various elements related to cognition. The neurocognitive battery consists of a cognitive assessment sequence of the following: WHO/UCLA Auditory Verbal Learning Test (WHO/UCLA AVLT) and Symbol Digit Modalities Test (SDMT). The major secondary endpoint for the cognitive dysfunction symptom cluster is a binary endpoint defined as an increase by at least 1 point in either or both of the AVLT delayed recall Z-score and/or SDMT number of correct substitutions Z-score, and no decrease exceeding 0.15 in either of these measures, at Day 90 compared to baseline.

The active stand test is performed to assess presence of orthostatic intolerance, orthostatic hypotension, and postural orthostatic tachycardia syndrome. The participant's blood pressure and heart rate are recorded after 5 minutes of lying and then at minutes 1, 3, 5, and 10 after standing. Changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate beats per minute (HR BPM) are assessed from lying to standing for 10 minutes. The major secondary endpoint for the autonomic dysfunction cluster is a binary endpoint defined as improvement in change from lying to standing in at least one of HR, DBP, or DBP from baseline to Day 90 (defined as an increase of at least 10mmHg in SBP, an increase of at least 5mmHg on DBP, or a decrease of at least 10 BPM on HR) and no worsening in any of HR, DBP, or DBP from baseline to Day 90 (defined as any decrease in SBP or DBP, or any increase in HR.

The endurance shuttle walk test (ESWT) is a performance measure that consists of timed walking on a 10 meter course. The major secondary endpoint for the exercise intolerance symptom cluster is defined as an increase of at least 3 minutes in walk time at Day 90 compared to baseline.

Each randomized participant was scheduled to take two doses of study drug per day for 25 days. The number of completed doses is calculated as 50 planned doses minus the number of planned missed doses.