RECOVER-AUTONOMIC (Ivabradine): Randomized Trial of the Effect of Ivabradine Versus Placebo on Long COVID Symptoms
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 181
- 试验地点
- 1
- 主要终点
- Change in Orthostatic Hypotension Questionnaire (OHQ)/Orthostatic Intolerance Questionnaire (OIQ) Composite Score
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
- •See NCT06305780 for RECOVER-AUTO: Platform Protocol level inclusion criteria which applies to this appendix (or sub-study)
- •Additional Appendix B (Ivabradine Sub-study) Level Inclusion Criteria:
- •1. Abnormal active standing test defined as presence of orthostatic tachycardia and experiencing orthostatic symptoms. Orthostatic tachycardia defined as: Increase of 30 beats per minute (bpm) or more in HR within 10 minutes upon standing without orthostatic hypotension (decline of ≥ 20 mmHg of systolic or ≥ 10 mmHg of diastolic blood pressure after 3 minutes of standing) OR History of documented increase of 30 bpm or more from an active stand test or tilt table test without orthostatic hypotension in the past 1 year AND standing HR above 100 bpm at the Screening/Baseline visit active stand test.
- •Exclusions Criteria:
- •See NCT06305780 for RECOVER-AUTO: Platform Protocol level inclusion criteria which applies to this appendix (or sub-study)
- •Additional Appendix B (Ivabradine Sub-study) Level
排除标准
- •A person of child-bearing potential who is not taking effective contraception
- •Use of midodrine, pyridostigmine, fludrocortisone, and guanfacine will be excluded unless participant is on a stable dose (>4 weeks). Participants on stable doses will be allowed to continue the medication throughout the study
- •Combination with verapamil or diltiazem which are moderate CYP3A4 inhibitors with heart rate reducing properties
- •Severe hepatic impairment
- •Use of drugs known to prolong the QT-interval (e.g., quinidine, disopyramide, bepridil, sotalol, amiodarone, pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidineUse of drugs known to prolong the QT-interval (e.g., quinidine, disopyramide, bepridil, sotalol, amiodarone, pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine
- •Concomitant use of digoxin or Paxlovid
- •Known history of atrial fibrillation or significant cardiac arrhythmia not due to reversible cause
- •Participants who are pacemaker dependent
- •Patients with hypokalemia (serum K+<3.5 mEq/L)
- •Patients taking potassium-depleting diuretics, unless potassium level is normal at the baseline CMP, in which case participants may continue taking it during the study.
- •A history of congenital or acquired long QT syndrome, with or without torsade de pointes
- •Patients with high degree AV block such as Type 2 AV block, Mobitz II
研究组 & 干预措施
Ivabradine + Coordinated Care
The starting dose will be 5 mg twice a day, and the dose will be modified if needed at the 1 month clinic visit. At this visit, HR will be measured and the dose will be modified as applicable. The maximum dose will be 7.5 mg twice daily if HR is ˃ 90 bpm.
The table below provides the dosing of ivabradine based on HR.
Supine Resting HR 60-80 2.5 mg BID Supine Resting HR >80 5 mg BID Supine Resting HR >90 7.5 mg BID
*Resting HR should be measured 5 minutes after lying down
干预措施: Ivabradine (Drug)
Ivabradine + Coordinated Care
The starting dose will be 5 mg twice a day, and the dose will be modified if needed at the 1 month clinic visit. At this visit, HR will be measured and the dose will be modified as applicable. The maximum dose will be 7.5 mg twice daily if HR is ˃ 90 bpm.
The table below provides the dosing of ivabradine based on HR.
Supine Resting HR 60-80 2.5 mg BID Supine Resting HR >80 5 mg BID Supine Resting HR >90 7.5 mg BID
*Resting HR should be measured 5 minutes after lying down
干预措施: Coordinated Care (Behavioral)
Ivabradine Placebo + Coordinated Care
干预措施: Ivabradine Placebo (Drug)
Ivabradine Placebo + Coordinated Care
干预措施: Coordinated Care (Behavioral)
Ivabradine + Usual Care
The starting dose will be 5 mg twice a day, and the dose will be modified if needed at the 1 month clinic visit. At this visit, HR will be measured and the dose will be modified as applicable. The maximum dose will be 7.5 mg twice daily if HR is ˃ 90 bpm.
The table below provides the dosing of ivabradine based on HR.
Supine Resting HR 60-80 2.5 mg BID Supine Resting HR >80 5 mg BID Supine Resting HR >90 7.5 mg BID
*Resting HR should be measured 5 minutes after lying down
干预措施: Ivabradine (Drug)
Ivabradine + Usual Care
The starting dose will be 5 mg twice a day, and the dose will be modified if needed at the 1 month clinic visit. At this visit, HR will be measured and the dose will be modified as applicable. The maximum dose will be 7.5 mg twice daily if HR is ˃ 90 bpm.
The table below provides the dosing of ivabradine based on HR.
Supine Resting HR 60-80 2.5 mg BID Supine Resting HR >80 5 mg BID Supine Resting HR >90 7.5 mg BID
*Resting HR should be measured 5 minutes after lying down
干预措施: Usual Care (Behavioral)
Ivabradine Placebo + Usual Care
干预措施: Ivabradine Placebo (Drug)
Ivabradine Placebo + Usual Care
干预措施: Usual Care (Behavioral)
结局指标
主要结局
Change in Orthostatic Hypotension Questionnaire (OHQ)/Orthostatic Intolerance Questionnaire (OIQ) Composite Score
时间窗: Baseline to End of Intervention (3 months)
The OHQ / OIQ is a measure of orthostatic intolerance and includes a 6-item symptom assessment (OHSA) and the 4-item Daily Activity Scale (OHDAS). Each item is scored from 0 (none/no interference) to 10 (worst possible/complete interference), describing the preceding week. The OHSA composite score is the average of the first 6 non-zero items and the OHDAS composite score is the average of the last 4 non-zero items. The OHQ/OIQ composite score is the average of the OHSA and OHDAS composite scores. The OHQ/OIQ scales at post-baseline are calculated using only those items that were included in the baseline scores.
次要结局
- Change in heart rate (HR)(Baseline to End of Intervention (3 months))
- Change in PROMIS-29 + 2 Questionnaire(Baseline to End of Intervention (3 months))
- Change in Composite Autonomic Symptoms Score 31 (COMPASS-31)(Baseline to End of Intervention (3 months))
- Change in Malmo POTS Symptom Score(Baseline to End of Intervention (3 months))
- Change in 6-min Walk Test(Baseline to End of Intervention (3 months))
- Characterize the safety and tolerability of study intervention for treatment of PASC(Baseline to Follow-up (6 months))
研究者
Kanecia Obie Zimmerman
Associate Professor of Pediatrics
Duke University