CaRe-ECMO Program on ECMO Weaning (CaRe-ECMO)

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

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).

Study Overview

• Status: Recruiting
• Conditions: Critical Illness
• Intervention / Treatment: Procedure: Cardiopulmonary rehabilitation; Procedure: Usual care

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 366
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yu Zheng, M.D.; Phone Number: 8617327081766; Email: yu.t.zheng@connect.polyu.hk
• Study Contact Backup: Name: Hao Sun, M.D.; Phone Number: 8613584017821; Email: Haosun@njmu.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Recruiting
      • The First Affiliated Hospital of Nanjing Medical University
      • Contact: Yu Zheng, M.D.; Phone Number: 8617327081766; Email: yu.t.zheng@connect.polyu.hk
      • Contact: Hao Sun, M.D.; Phone Number: 8613584017821; Email: Haosun@njmu.edu.cn
      • Principal Investigator: Xufeng Chen, M.D.
      • Principal Investigator: Jingsong Zhang, M.D.
      • Principal Investigator: Xiao Lu, M.D.
      • Sub-Investigator: Yu Zheng, M.D.
      • Sub-Investigator: Hao Sun, M.D.
      • Sub-Investigator: Yong Mei, M.D.
      • Sub-Investigator: Yongxia Gao, MSc.
      • Sub-Investigator: Jinru Lv, MSc.
      • Sub-Investigator: Dijia Pan, MSc.
      • Sub-Investigator: Lu Wang, Mphil.
      • Sub-Investigator: Xintong Zhang, M.D.
      • Sub-Investigator: Deliang Hu, MSc.
      • Sub-Investigator: Feng Sun, M.D.
      • Sub-Investigator: Wei Li, M.D.
      • Sub-Investigator: Gang Zhang, MSc.
      • Sub-Investigator: Huazhong Zhang, MSc.
      • Sub-Investigator: Ying Chen, BSc.
      • Sub-Investigator: Shenrui Wang, BSc.
      • Sub-Investigator: Zhongman Zhang, MSc.
      • Sub-Investigator: Baoquan Li, BSc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CaRe-ECMO group; Patients in the CaRe-ECMO group will be treated with usual care, ECMO therapy, and cardiopulmonary rehabilitation program.	Procedure: Cardiopulmonary rehabilitation; 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.; Procedure: Usual care; 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.
Placebo Comparator: Control group; Usual care and ECMO therapy	Procedure: Usual care; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Investigators: Principal Investigator: Xiao Lu, M.D., The First Affiliated Hospital with Nanjing Medical University; Principal Investigator: Jingsong Zhang, M.D., The First Affiliated Hospital with Nanjing Medical University; Principal Investigator: Xufeng Chen, M.D., The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2021
• Primary Completion (Anticipated): June 30, 2025
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: September 1, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 15, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Open-label; Weaning; Extracorporeal Membrane Oxygenation; Multidisciplinary; Cardiopulmonary Rehabilitation
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: CaRe-ECMO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No