RECOVER-VITAL: A Platform Protocol for Evaluation of Interventions for Viral Persistence, Viral Reactivation, and Immune Dysregulation in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 964
- 试验地点
- 1
- 主要终点
- Change in cognitive dysfunction symptom cluster, as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) cognitive function T-score
研究概览
简要总结
This is an appendix of master protocol (NCT05595369) 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 sub-study is a prospective, multi-center, double-blind, randomized, controlled trial evaluating nirmatrelvir/ritonavir (Paxlovid) in two dosing durations for the treatment of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). The study is evaluating potential mechanisms of action, efficacy, and safety of antivirals and other therapeutics in individuals with PASC, according to the platform protocol objectives. The hypothesis is that persistent viral infection and/or overactive/chronic immune response and 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.
详细描述
For this appendix of the master protocol (NCT05595369), participants will be randomized to Paxlovid (nirmatrelvir/ritonavir) vs. ritonavir control plus nirmatrelvir-matching placebo.
When there are multiple study interventions (sub-studies) available under the master protocol (NCT05595369), randomization will occur based on the specific inclusion/exclusion criteria of each appendix.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double-blind
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •See NCT NCT05595369 for RECOVER-VITAL: Platform Protocol level
排除标准
- •which applies to this appendix
- •Additional Appendix Level Exclusion Criteria:
- •Known pregnancy*
- •Active or expected breastfeeding during the study
- •Known eGFR < 30 mL/min
- •Known severe hepatic impairment (Child-Pugh Class C)
- •Current use of drugs highly dependent on CYP3A for clearance** and for which elevated concentrations are associated with serious and/or life-threatening reactions and which cannot be interrupted during the time of study administration and within seven days before and after study drug administration
- •Current use of potent CYP3A inducers** where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance
- •A pregnancy test must be performed at the Baseline Visit for participants who are capable of becoming pregnant.
- •A guide of drugs that may be contraindicated are listed in Section 4 CONTRAINDICATIONS of the Full Prescribing Information of the EUA for PAXLOVID. https://labeling.pfizer.com/ShowLabeling.aspx?id=16474&format=pdf
研究组 & 干预措施
Paxlovid 25 day dosing
Paxlovid (nirmatrelvir 300mg, ritonavir 100mg) bid x 25 days
干预措施: Paxlovid 25 day dosing (Drug)
Paxlovid 15 day dosing
Paxlovid (nirmatrelvir 300mg, ritonavir 100mg) bid x 15 days then ritonavir 100mg plus nirmatrelvir-matching placebo x 10 days
干预措施: Paxlovid 15 day dosing (Drug)
Control
ritonavir 100mg plus nirmatrelvir-matching placebo bid x 25 days
干预措施: Control (Drug)
结局指标
主要结局
Change in cognitive dysfunction symptom cluster, as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) cognitive function T-score
时间窗: Baseline to Day 90
The PROMIS cognitive function-8a (PRO assessment) T-score 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 90 days compared to baseline.
Change in autonomic dysfunction symptom cluster, as measured by the orthostatic hypotension questionnaire (OHQ)
时间窗: Baseline to 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 90 days compared to baseline.
Change in exercise intolerance symptom cluster, as measured by the Modified Depaul Symptom Questionnaire-Post Exertional Malaise (DSQ-PEM)
时间窗: Baseline to 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 1-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. For exercise intolerance, the primary endpoint 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.
次要结局
- Change in cognitive dysfunction symptom cluster, as measured by a neurocognitive battery(Baseline to Day 90)
- Change in autonomic dysfunction symptom cluster, as measured by the active stand test(Baseline to Day 90)
- Change in exercise intolerance symptom cluster, as measured by the endurance shuttle walk test (ESWT)(Baseline to Day 90)
- Occurrence of individual SAEs(Baseline to Day 190)
- Occurrence of one or more SAEs(Baseline to Day 190)
- Occurrence of AEs and SAEs leading to discontinuation(Baseline to Day 25)
- Occurrence of Events of Special Interest (ESIs)(Baseline to Day 190)
- Adherence in intervention versus control groups as measured by number of missed doses(Baseline to Day 25)
研究者
Kanecia Obie Zimmerman
Associate Professor of Pediatrics
Duke University