RECOVER-AUTONOMIC: A Platform Protocol for Evaluation of Interventions for Autonomic Dysfunction 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
- 381
- 试验地点
- 100
- 主要终点
- Total number of participants enrolled in each Appendix
研究概览
简要总结
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, randomized, controlled platform trial evaluating various interventions for use in the treatment of autonomic dysfunction symptoms, including cardiovascular complications and postural orthostatic tachycardia syndrome (POTS), in PASC participants. The interventions tested will include non-pharmacologic care and pharmacologic therapies with study drugs.
详细描述
The hypothesis is that some of the autonomic dysfunction symptoms are immune-mediated, so immunotherapy and other applicable therapies will result in improvement in autonomic symptoms.
Interventions will be added to the platform protocol as appendices. Each appendix will leverage all elements of the platform protocol, with additional elements described in the individual 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
- •≥ 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 Organization12ɸ ɸ Enrollment of participants with suspected or probable SARS-CoV-2 infection will only be allowed if they occurred before May 1, 2021 and be limited to no more than 10% of the total sample size per Study Drug Appendix. Refer to the Manual of Procedures (MOP) for details.
- •Suspected case of SARS-CoV-2 infection - Three options, A through C:
- •A. 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, dyspnea, nausea, diarrhea, anorexia.
- •Epidemiological criteria: Contact of a probable or confirmed case or linked to a COVID-19 cluster; or B. Presents with 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. Presents 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, defined as meets clinical criteria above AND is a contact of a probable or confirmed case or is linked to a COVID-19 cluster.
- •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.
- •Moderate, self-identified autonomic symptoms (defined as COMPASS-31 >20) following a SARS-CoV-2 infection that has persisted for at least 12 weeks and is still present at the time of consent
- •OHQ/OIQ, question 1 score >2
排除标准
- •Known pregnancy, breast-feeding, or contemplating pregnancy during the study period
- •Known active acute SARS-CoV-2 infection ≤ 4 weeks from enrollment
- •Known renal failure (eGFR <20ml/1.73 m²)
- •Known atrial fibrillation or significant cardiac arrhythmia
- •Known cardiovascular conditions such as heart failure (Class 3-4), severe valvular disease
- •Clinically significant atherosclerotic disease, defined as history of stroke or myocardial infarction or revascularization 6 months prior to enrollment and/or current symptomatic angina
- •Existing uncontrolled hypertension
- •Inability to comply with the protocol
- •Any condition that the investigator believes makes it inappropriate to treat with study intervention, including severe debility.
- •History of POTS or significant dysautonomia before COVID-19 index infection
- •Enrolled in another clinical trial or another study intervention appendix in this platform protocol * Patients who are a part of observational studies (e.g. imaging) may be included in this trial. Participants may enroll in another interventional trial or re-enroll in this trial for a different study intervention appendix 30 days after end of study (Follow-up visit).
研究组 & 干预措施
Ivabradine
In the ivabradine study, randomization will be implemented with 1:1:1:1 allocation among the combinations of ivabradine/placebo and coordinated/usual care. All participants receive either ivabradine or placebo for 3 months (12 weeks) with a follow-up period for an additional 3 months (total study duration of 6 months). See NCT06305806 for additional details.
干预措施: Ivabradine + Coordinated Care (Drug)
Intravenous immunoglobulin (IVIG)
In the IVIG study, randomization will be implemented with 1:1:1:1 allocation among the combination of IVIG/placebo and coordinated/ usual non-pharmacologic care. All participants will receive IVIG or placebo for 9 months (36 weeks) with a follow-up period for an additional 3 months (total study duration for 12 months). See NCT06305793 for additional details.
干预措施: IVIG + Coordinated Care (Drug)
Intravenous immunoglobulin (IVIG)
In the IVIG study, randomization will be implemented with 1:1:1:1 allocation among the combination of IVIG/placebo and coordinated/ usual non-pharmacologic care. All participants will receive IVIG or placebo for 9 months (36 weeks) with a follow-up period for an additional 3 months (total study duration for 12 months). See NCT06305793 for additional details.
干预措施: IVIG Placebo + Coordinated Care (Drug)
Intravenous immunoglobulin (IVIG)
In the IVIG study, randomization will be implemented with 1:1:1:1 allocation among the combination of IVIG/placebo and coordinated/ usual non-pharmacologic care. All participants will receive IVIG or placebo for 9 months (36 weeks) with a follow-up period for an additional 3 months (total study duration for 12 months). See NCT06305793 for additional details.
干预措施: IVIG + Usual Care (Drug)
Intravenous immunoglobulin (IVIG)
In the IVIG study, randomization will be implemented with 1:1:1:1 allocation among the combination of IVIG/placebo and coordinated/ usual non-pharmacologic care. All participants will receive IVIG or placebo for 9 months (36 weeks) with a follow-up period for an additional 3 months (total study duration for 12 months). See NCT06305793 for additional details.
干预措施: IVIG Placebo + Usual Care (Drug)
Ivabradine
In the ivabradine study, randomization will be implemented with 1:1:1:1 allocation among the combinations of ivabradine/placebo and coordinated/usual care. All participants receive either ivabradine or placebo for 3 months (12 weeks) with a follow-up period for an additional 3 months (total study duration of 6 months). See NCT06305806 for additional details.
干预措施: Ivabradine Placebo + Coordinated Care (Drug)
Ivabradine
In the ivabradine study, randomization will be implemented with 1:1:1:1 allocation among the combinations of ivabradine/placebo and coordinated/usual care. All participants receive either ivabradine or placebo for 3 months (12 weeks) with a follow-up period for an additional 3 months (total study duration of 6 months). See NCT06305806 for additional details.
干预措施: Ivabradine + Usual Care (Drug)
Ivabradine
In the ivabradine study, randomization will be implemented with 1:1:1:1 allocation among the combinations of ivabradine/placebo and coordinated/usual care. All participants receive either ivabradine or placebo for 3 months (12 weeks) with a follow-up period for an additional 3 months (total study duration of 6 months). See NCT06305806 for additional details.
干预措施: Ivabradine Placebo + Usual Care (Drug)
结局指标
主要结局
Total number of participants enrolled in each Appendix
时间窗: Baseline to End of Intervention (IVIG 9 months, Ivabradine 3 months)
Total number of participants enrolled in each Appendix will be reported. Appendix-specific outcome measure data will be reported under the associated NCT#
Total Number of Participants Enrolled in Each Appendix
时间窗: During the enrollment period, approximately 16 months
次要结局
未报告次要终点
研究者
Kanecia Obie Zimmerman
Associate Professor of Pediatrics
Duke University