SARS CoV-2 Viral Persistence Study (PASC) - Study of Long COVID-19 (PASC)
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|ClinicalTrials.gov Identifier: NCT05595369|
Recruitment Status : Not yet recruiting
First Posted : October 27, 2022
Last Update Posted : October 27, 2022
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This study is a platform protocol designed to be flexible so that it is suitable for a wide range of settings within health care systems and in community settings where it can be integrated into COVID-19 programs and subsequent treatment plans.
This protocol is a prospective, multi-center, multi-arm, double-blind, randomized, controlled platform trial evaluating antiviral and other therapeutics for use in the treatment of Post-Acute Sequelae of COVID-19 (PASC). The hypothesis is that persistent viral infection (antigenemia) and/or overactive/chronic immune response (inflammation) are underlying contributors to PASC and that antiviral and other applicable therapies may result in viral clearance or decreased inflammation and improvement in PASC symptoms.
|Condition or disease||Intervention/treatment||Phase|
|Long COVID||Drug: Paxlovid Drug: Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||1700 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||As part of screening, potential participants will answer symptom questions. Eligible participants will complete Symptom Cluster assessments at the Baseline visit based on their responses to symptom questions at screening. Participants will subsequently be assigned to one or more of the three Symptom Clusters based on the baseline assessments. Participants must meet certain criteria within a specific symptom cluster in order to be included in the cluster. After study enrollment and initial cluster assignment, further assessments will be performed among participants who meet the symptom cluster criteria. Participants whose answers qualify them for additional screening for > 1 symptom cluster will undergo assessments for all of the symptom clusters for which the participant qualifies.|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||Efficacy of Antivirals and Other Therapeutics for Treatment of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)|
|Estimated Study Start Date :||January 17, 2023|
|Estimated Primary Completion Date :||January 17, 2024|
|Estimated Study Completion Date :||January 17, 2024|
PAXLOVID dosage is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet). All three tablets (two of nirmatrelvir and one of ritonavir) must be taken together and no more than 15 minutes apart. All three tablets are taken together twice daily by mouth for 15 days.
PAXLOVID dosage is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet).
Placebo Comparator: Placebo
The control formulation includes two placebo tablets and one ritonavir tablet.
The control formulation includes two placebo tablets and one ritonavir tablet.
- Change in Exercise intolerance symptom cluster, as measured by the Modified Depaul Symptom Questionnaire-Post Exertional Malaise (DSQ-PEM) [ Time Frame: Baseline to End of Study (Day 90) ]DSQ-PEM assesses symptom frequency and severity over a 6-month look back period, however, for the purposes of this study, it will be modified to assess over a 2-week 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. Post-Exertional Malaise (PEM) will be deemed to be present if the participant reports having at least one moderate (rated severity ≥ 2) PEM symptom for a frequency rated ≥ 2.
- Change in Cognitive dysfunction symptom cluster, as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) cognitive function T-score [ Time Frame: Baseline to End of Study (Day 90) ]The PROMIS cognitive function (PRO assessment) T-score (consisting of 29 items that assess general domains of health and functioning, including overall physical health, mental health, social health, pain, fatigue, and overall perceived quality of life) is a quantitative measure of current cognitive function. The primary endpoint for cognitive dysfunction is improvement of at least 5 T-score points on the PROMIS-cognitive function as measured at End of Study compared to baseline.
- Change in Autonomic dysfunction symptom cluster, as measured by the orthostatic hypotension questionnaire (OHQ) [ Time Frame: Baseline to End of Study (Day 90) ]The OHQ [Orthostatic Hypotension Questionnaire [PRO assessment)] is a measure of orthostatic intolerance, which has been the primary presentation of patients with PASC-related autonomic dysfunction. This measure includes the Orthostatic Intolerance Daily Activity Scale (OIDAS) and the Orthostatic Intolerance Symptom Assessment (OISA). The primary endpoint for autonomic dysfunction is improvement in autonomic function as defined by a ≥ 1-point decrease in the OHQ question 1 at End of Study compared to baseline.
- Change in Exercise intolerance symptom cluster, as measured by the endurance shuttle walk test (ESWT) [ Time Frame: Baseline to End of Study (Day 90) ]The ESWT [Endurance shuttle walk test (performance measure)] consists of timed walking on a 10m course.The ESWT will primarily be analyzed as a binary endpoint defined as an increase of at least 3 minutes of walking time at follow-up compared to baseline.
- Change in Cognitive dysfunction symptom cluster, as measured by a neurocognitive battery [ Time Frame: Baseline to End of Study (Day 90) ]The neurocognitive battery outcome is a binary indicator of whether the participant has evidence of deficits (at least one standard deviation below the mean on at least one test within the battery).
- Change in Autonomic dysfunction symptom cluster, as measured by the Active stand test [ Time Frame: Baseline to End of Study (Day 90) ]The active stand test outcome is a binary indicator of whether the follow-up active stand test result was abnormal or normal.
- Proportion of participants who experience individual SAEs [ Time Frame: Baseline to End of Study (Day 90) ]
- Proportion of participants who experience any one or more SAEs [ Time Frame: Baseline to End of Study (Day 90) ]
- Incidence of SAEs leading to discontinuation [ Time Frame: Baseline to End of Study (Day 90) ]
- Incidence of Events of Special Interest (ESIs) [ Time Frame: Baseline to End of Study (Day 90) ]
- Change in viral biomarker, antigenemia, assessed via the Brigham and Women's Hospital (BWH) Spike protein antigen assay [ Time Frame: Baseline, End Of Dosing (Day 15), Day 30, Day 60, and End of Study (Day 90) ]
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- ≥ 18 years of age at the time of enrollment
Previous suspected, probable, or confirmed SARS-CoV-2 infection, as defined by the Pan American Health Organization Enrollment of participants with suspected or probable SARS-CoV-2 infection will be limited to no more than 25% of the total sample size per Study Drug Appendix.
Suspected case of SARS-CoV-2 infection - Three options, A through C:
A. A person who meets the clinical OR epidemiological criteria. Clinical criteria: Acute onset of fever AND cough (influenza-like illness) OR Acute onset of ANY THREE OR MORE of the following signs or symptoms: fever, cough, general, weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnoea, nausea, diarrhea, anorexia. Epidemiological criteria: Contact of a probable or confirmed case or linked to a COVID-19 cluster; or B. Acute respiratory infection with history of fever or measured fever of ≥ 38°C; and cough; with onset within the last 10 days; and who requires hospitalization); or C. With no clinical signs or symptoms, NOR meeting epidemiologic criteria with a positive professional use or self-test SARS-CoV-2 antigen-Rapid Diagnostic Test.
Probable case of SARS-CoV-2 infection - Two options, A through B:
A. A patient who meets clinical criteria above AND is a contact of a probable or confirmed case or is linked to a COVID-19 cluster; or B. Death, not otherwise explained, in an adult with respiratory distress preceding death AND who was a contact of a probable or confirmed case or linked to a COVID-19 cluster (Not applicable for this trial).
Confirmed case of SARS-CoV-2 infection - Two options, A through B:
A. A person with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or B. Meeting clinical criteria AND/OR epidemiological criteria (See suspect case A). With a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test.
At least one moderate cluster-associated symptom identified via the Cluster Targeted COVID-19 Symptom Questions (CTCSQ), with participant identifying new/worse symptoms >4 weeks since COVID-19 illness and having persisted for at least 8 weeks*
*Enrollment of participants with symptoms of PASC for a duration of > 1 year will be limited to a maximum of 40% of the total sample size.
- Meeting patient reported outcome (PRO) Symptom Cluster criteria for at least one Symptom Cluster
- Willing and able to provide informed consent, complete the surveys, clinical assessments, and return for all of the necessary follow-up visits
An individual who meets any of the following criteria will be excluded from participation in this study:
- Known active acute SARS-CoV-2 infection
- Known prior diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome, not related to SARS-CoV-2 infection
- Known pre-existing dysautonomia, not related to SARS-CoV-2 infection
- Known stroke within 3 months of enrollment
- Known severe anemia, defined as < 8 g/dL21
Meeting the following symptom cluster exclusion for all eligible clusters#:
- Exercise intolerance: Participants will be excluded from the symptom cluster if they have had any of the following within 4 weeks of enrollment - an acute myocardial infarction or unstable angina, uncontrolled arrhythmias causing symptoms or hemodynamic compromise, acute myocarditis or pericarditis, uncontrolled acutely decompensated heart failure (acute pulmonary edema), acute pulmonary embolism, suspected dissecting aneurysm, severe hypoxemia at rest, or any acute disorder that may affect exercise performance; or if they are aggravated by exercise (e.g., infection, thyrotoxicosis, unable to cooperate)
- Cognitive dysfunction: Participants will be excluded if they have known prior cognitive dysfunction not related to COVID-19
- Autonomic dysfunction: Participants will be excluded if they have atrial fibrillation or significant cardiac arrhythmia, more than moderate alcohol consumption, pre-existing sustained severe hypertension (BP>180/110mmHg in the sitting position) #Participants who are eligible for > 1 cluster must meet all inclusion and no exclusion criteria for an individual symptom cluster. If not, they will be excluded from that individual symptom cluster.
ɣ Defined as greater than 2 drinks a day for men and 1 drink a day for women.22
- Known diagnosis of Lyme disease
- Any non-marijuana illicit drug use within 30 days of informed consent
- Current or recent use (within the last 14 days) of study drug*
- Known allergy/sensitivity or any hypersensitivity to components of the study drug or control*
- Known contraindication(s) to study drug including prohibited concomitant medications and without ability to safely hold prohibited concomitant medications
- Inability to discontinue symptomatic medications for the identified time periods
Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study
- If only one study drug appendix is open at the time of enrollment. If multiple study drug appendices are open, a participant may be excluded from any study drug appendix based on contraindications listed in the study drug appendix, current use of study drug, or known allergy/sensitivity/hypersensitivity and still remain eligible for the remaining study drug appendices.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05595369
|Contact: Rachel E Olson, RN MS MBA PMPemail@example.com|
|Contact: Barrie L Harper, BSMT (ASCP) PMPfirstname.lastname@example.org|
|Principal Investigator:||Kanecia O Zimmerman, MD PhD||Duke University|
|Responsible Party:||Kanecia Obie Zimmerman, Associate Professor of Pediatrics, Duke University|
|Other Study ID Numbers:||
OTA-21-015G ( Other Grant/Funding Number: NIH grant to RTI; RTI subcontracting with DCRI )
|First Posted:||October 27, 2022 Key Record Dates|
|Last Update Posted:||October 27, 2022|
|Last Verified:||October 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Plan Description:||We will share the summary of results on the study website: https://recovercovid.org/|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|