CaRe-ECMO Program on ECMO Weaning

Study Overview
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Brief Summary
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Mortality of patients suffering critical illness has been dramatically improved with advanced technological development of extracorporeal membrane oxygenation (ECMO) therapy. However, weaning rate stayed low in a majority of ECMO-supported patients. As one of several options, cardiopulmonary rehabilitation serves as effective intervention in the improvement of cardiovascular and respiratory function in various major critical illness. Nonetheless, its roles in facilitating ECMO weaning has not yet been explored. The purpose of this study is to investigate the effectiveness of cardiopulmonary rehabilitation on rate of ready for weaning in ECMO-supported patients (CaRe-ECMO).

Detailed Description
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Studies have documented that rate of mechanical ventilation weaning was improved in patients received early rehabilitation intervention while its effectiveness in ECMO weaning remains unclear. This inspires us to hypothesize that if the medical rationale is based on its assumed benefits on cardiac function and oxygenation, then cardiopulmonary rehabilitation may subsequently contribute to earlier weaning of ECMO. The CaRe-ECMO trial is a prospective, multidisciplinary, randomized controlled, parallel group, clinical trial. Cardiopulmonary rehabilitation program which encompasses six evidence-based components:1) positioning; 2) passive range of motion (PROM) training; 3) neuromuscular electronic stimulation (NMES); 4) surface electrical phrenic nerve stimulation (SEPNS); 5) respiratory PNF techniques 6) airway clearance techniques; 366 ECMO-supported patients in department of emergency medicine will be randomized to control and CaRe-ECMO group. CaRe-ECMO group will be treated with usual care, ECMO therapy, and cardiopulmonary rehabilitation program. Usual care normally comprises pharmacotherapy, mechanical ventilation, continuous renal replacement therapy (CRRT), intra-aortic balloon pump (IABP), and specific nursing for ECMO therapy and their original injuries, as appropriate. Control group will be treated with usual care, ECMO therapy. The primary objective of the CaRe-ECMO trial is to investigate the impact of cardiopulmonary rehabilitation combined with usual care on rate of ready for ECMO weaning at CaRe-ECMO Day 7, when compared to usual care alone. Secondary objectives are to evaluate the effects of cardiopulmonary rehabilitation on rate of ECMO weaning, total length of ready for ECMO weaning, total length of ECMO weaning, rate of mechanical ventilation weaning, total length of mechanical ventilation, all-cause mortality, rate of major post-ECMO complications, diaphragmatic thickness and mobility, ECMO Unit length of stay (LOS), total hospital LOS, total cost for hospitalization, cerebral performance category (CPC) index, activity of daily living (ADL), and health related quality of life (HRQoL). The CaRe-ECMO trial is designed to test the hypothesis that early cardiopulmonary rehabilitation can accelerate weaning of ECMO-supported patients. If CaRe-ECMO trial results in superior improvement in primary and secondary outcomes, it will offer an innovative treatment option for ECMO-supported patients.

Official Title
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Impact of Cardiopulmonary Rehabilitation on Weaning of Extracorporeal Membrane Oxygenation (CaRe-ECMO): a Prospective Multidisciplinary Randomized Controlled Clinical Trial

Conditions
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Critical Illness

Intervention / Treatment
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* Procedure: Cardiopulmonary rehabilitation
* Procedure: Usual care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1) Aged 18yr or order 2) Eligible for receiving ECMO (veno-venous [VV] or veno-arterial [VA]) therapy 3) With mechanical ventilation 4) With stable condition and eligible for cardiopulmonary rehabilitation after 72 hours of ECMO 5) With no contraindications for cardiopulmonary rehabilitation 6) With a life expectancy of more than 3 days 7) Sign informed consent form by the guardian Exclusion Criteria: 1) Pregnant 2) Use ECMO as a bridge to recovery or definitive treatment (e.g. lung transplantation or heart transplantation) 3) Enrolled in another trial previously

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CaRe-ECMO group<br>Patients in the CaRe-ECMO group will be treated with usual care, ECMO therapy, and cardiopulmonary rehabilitation program. | Procedure: Cardiopulmonary rehabilitation<br>* Cardiopulmonary rehabilitation program which encompasses six evidence-based components according to literature review: 1) positioning; 2) passive range of motion (PROM) training; 3) neuromuscular electronic stimulation (NMES); 4) surface electrical phrenic nerve stimulation (SEPNS); 5) PNF techniques; and 6) airway clearance techniques; Usual care normally comprises pharmacotherapy, mechanical ventilation, continuous renal replacement therapy (CRRT), intra-aortic balloon pump (IABP), and specific nursing for ECMO therapy and their original injuries, as appropriate.<br>Procedure: Usual care<br>* Control group will be treated with usual care and ECMO therapy. Usual care normally comprises pharmacotherapy, mechanical ventilation, continuous renal replacement therapy (CRRT), intra-aortic balloon pump (IABP), and specific nursing for ECMO therapy and their original injuries, as appropriate.<br>|
| Placebo Comparator: Control group<br>Usual care and ECMO therapy | Procedure: Usual care<br>* Control group will be treated with usual care and ECMO therapy. Usual care normally comprises pharmacotherapy, mechanical ventilation, continuous renal replacement therapy (CRRT), intra-aortic balloon pump (IABP), and specific nursing for ECMO therapy and their original injuries, as appropriate.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of ready for ECMO weaning at CaRe-ECMO Day 7 | Rate of ready for ECMO weaning will be calculated 7 days after cardiopulmonary rehabilitation delivery | CaRe-ECMO Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of ready for ECMO weaning | Rate of ready for ECMO weaning will be calculated 14, 30 and 90 days after cardiopulmonary rehabilitation delivery | CaRe-ECMO Day 14, 30 and 90 | 
| Rate of ECMO weaning | Rate of ECMO weaning will be calculated according to date of ECMO weaning fulfilled | CaRe-ECMO Day 7, 14, 30 and 90 | 
| Total length of ready for ECMO weaning | Total length of ready for ECMO weaning refers to exact length in day till patients fulfill all criteria of ready for ECMO weaning according to daily checkout records | From date of ECMO initiation until the date of ready for ECMO weaning, assessed up to CaRe-ECMO Day 90 | 
| Total length of ECMO weaning | Total length of ECMO weaning refers to exact length in day for patients treated with ECMO therapy | From date of ECMO initiation until the date of ECMO weaning, assessed up to CaRe-ECMO Day 90 | 
| Rate of mechanical ventilation weaning | Rate of mechanical ventilation weaning will be calculated according to date of mechanical ventilation weaning fulfilled. Daily screening of mechanical ventilation weaning will be strictly performed with checklist | CaRe-ECMO Day 7, 14, 30 and 90 | 
| Total length of mechanical ventilation | Total length of mechanical ventilation refers to exact length in day for patients treated with mechanical ventilation | From date of mechanical ventilation initiation until the date of mechanical ventilation weaning, assessed up to CaRe-ECMO Day 90 | 
| All-cause mortality | All-cause mortality is defined as rate of death due to any causes and will be calculated according to date of death | CaRe-ECMO Day 7, 14, 30 and 90 | 
| Major complications | Rate of complications occurred after ECMO, including but not limited to ECMO related complications (e.g., thromboembolism), mechanical ventilation related complications (e.g., pneumonia), newly developed myocardial infarction, acute kidney injury, neurologic events (e.g., stroke, seizures), and multiple organ failure | CaRe-ECMO Day 7, 14, 30 and 90 | 
| Diaphragmatic thickness and mobility | Diaphragmatic thickness and mobility refer to ultrasound guided evaluation of diaphragmatic thickness and mobility under M mode | Every three days, assessed up to CaRe-ECMO Day 90 | 
| ECMO Unit length of stay (LOS) | ECMO Unit length of stay (LOS) accounts for length in day for patients' stay in the ECMO Unit | Discharge day (discharge from ECMO Unit), assessed up to CaRe-ECMO Day 90 | 
| Total hospital length of stay | Total hospital LOS accounts for total hospital LOS in day for patients' stay in both ECMO Unit and other departments | Discharge day (discharge from hospital), assessed up to CaRe-ECMO Day 90 | 
| Total cost for hospitalization | Total cost for hospitalization will be calculated by addition of the cost of all units and departments admission | Discharge day (discharge from hospital), assessed up to CaRe-ECMO Day 90 | 
| Cerebral performance category (CPC) index | Cerebral performance category (CPC) index will be recorded, for those successfully weaning of ECMO, to reflect post-ECMO neurological status | CaRe-ECMO Day 7, 14, 30, 90 and discharge day (discharge from ECMO Unit), assessed up to CaRe-ECMO Day 90 | 
| Activity of daily living (ADL) | Activity of daily living (ADL) will be evaluated, for those successfully weaning of ECMO, with Katz Index | CaRe-ECMO Day 7, 14, 30, 90 and discharge day (discharge from ECMO Unit), assessed up to CaRe-ECMO Day 90 | 
| Health related quality of life (HRQoL) | Health related quality of life (HRQoL) will be measured, for those successfully weaning of ECMO, with SF-12 | CaRe-ECMO Day 7, 14, 30, 90 and discharge day (discharge from ECMO Unit), assessed up to CaRe-ECMO Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Extracorporeal Membrane Oxygenation, Cardiopulmonary Rehabilitation, Weaning, Multidisciplinary, Randomized controlled trial, Open-label