RECOVER-AUTONOMIC (IVIG): Randomized Trial of the Effect of IVIG 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
- 200
- 试验地点
- 2
- 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 Post-Acute Sequelae of SARS-CoV-2 infection (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 A (IVIG Sub-study) Level Inclusion Criteria:
- •Abnormal active standing test defined as presence of orthostatic tachycardia (an increase of 30 beats per minute (bpm) or more in HR within 10 minutes upon standing without orthostatic hypotension) and experiencing orthostatic symptoms
- •COMPASS-31 Score > 40
排除标准
- •See NCT06305780 for RECOVER-AUTO: Platform Protocol level exclusion criteria which applies to this appendix (or sub-study)
- •Additional Appendix A (IVIG Sub-study) Level Exclusion Criteria:
- •Current or previous IVIG treatment
- •Contraindication to intravenous immunoglobulin.
- •Known allergic reactions to blood products including IVIG and/or subcutaneous immunoglobulin (SCIG), such as history of clinically relevant hemolysis after IVIG infusion, aseptic meningitis, recurrent severe headache, hypersensitivity, severe generalized or severe local skin reactions
- •Selective IgA deficiency
- •Current and recent (within 5 half-lives) use of high-dose corticosteroids (for example for prior solid organ transplant), omalizumab, anti-TNF-alpha inhibitors
- •Use of immunosuppressants such as Plaquenil, or low-dose steroid (prednisone, no more than 10mg a day) will be excluded unless the participant is on stable (>4 weeks) dose
- •Significant thrombotic events after the acute phase of COVID-19 and/or within 6 months of enrollment
- •Veins that are not viable for infusions
- •Not willing to adhere to dosing schedule for IVIG infusions for 9 months
研究组 & 干预措施
IVIG + Coordinated Care
IVIG (Gamunex); 2g /kg monthly for 9 months (36 weeks)
干预措施: IVIG (intravenous immunoglobulin) (Drug)
IVIG + Coordinated Care
IVIG (Gamunex); 2g /kg monthly for 9 months (36 weeks)
干预措施: Coordinated Care (Behavioral)
IVIG Placebo + Coordinated Care
Saline: Same dosage as IVIG; monthly for 9 months (36 weeks)
干预措施: IVIG Placebo (Drug)
IVIG Placebo + Coordinated Care
Saline: Same dosage as IVIG; monthly for 9 months (36 weeks)
干预措施: Coordinated Care (Behavioral)
IVIG + Usual Care
IVIG (Gamunex); 2g /kg monthly for 9 months (36 weeks)
干预措施: IVIG (intravenous immunoglobulin) (Drug)
IVIG + Usual Care
IVIG (Gamunex); 2g /kg monthly for 9 months (36 weeks)
干预措施: Usual Care (Behavioral)
IVIG Placebo + Usual Care
Saline: Same dosage as IVIG; monthly for 9 months (36 weeks)
干预措施: IVIG Placebo (Drug)
IVIG Placebo + Usual Care
Saline: Same dosage as IVIG; monthly for 9 months (36 weeks)
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 (9 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 step count as measured by a wearable device(Baseline to End of Intervention (9 months))
- Change in heart rate (HR)(Baseline to End of Intervention (9 months))
- Change in Active Stand Test(Baseline to End of Intervention (9 months))
- Change in blood pressure(Baseline to End of Intervention (9 months))
- Change in 6-min Walk Test(Baseline to End of Intervention (9 months))
- Change in heart rate as measured by a wearable device(Baseline to End of Intervention (9 months))
- Change in Composite Autonomic Symptoms Score 31 (COMPASS-31)(Baseline to End of Intervention (9 months))
- Change in Patient-Reported Outcomes Measurement Information System (PROMIS-29) + 2 Questionnaire(Baseline to End of Intervention (9 months))
- Change in Malmo POTS Symptom Score(Baseline to End of Intervention (9 months))
- Proportion of participants who experience individual (SAEs(Baseline to Follow-up (12 months))
- Proportion who experience any one or more ( Serious Adverse Event) SAEs(Baseline to Follow-up (12 months))
- Incidence of SAEs leading to discontinuation(Baseline to Follow-up (12 months))
- Incidence of Events of Special Interest (ESIs)(Baseline to Follow-up (12 months))
研究者
Kanecia Obie Zimmerman
Associate Professor of Pediatrics
Duke University