Evaluation of Early CRRT InTerventions in Patients With ECMO(ELITE)

NCT03549923 | Completed Phase 4 DMC

• 1 other identifier: 2016YFC1301000
• Study Type: interventional
• Target: 131
• Locations: 1 country
• Sites: 1

Brief Summary

Extracorporeal membrane oxygenation (ECMO) is of great value in supporting patients with cardiac shock. More than 80% ECMO patients will develop renal catastrophe that continuous renal replacement therapy (CRRT) is required. The evidence is conflict as to whether early CRRT improves outcomes. Early CRRT before a definite indication developed may prevent side effects of toxicity and fluid overload and therefore, bring survival benefit for the patient. This hypothesis need to be tested in RCT. Plasma catecholamine levels can be very high in patients under VA-ECMO, which maybe toxic to the cardiac myocardium. Beta-blockers can antagonize the effects of catecholamine. In patients with VA-ECMO, the protective effect of beta-blocker may improve the patients' outcome. This hypothesis also need to be tested in RCT. ELITE (Evaluation of Early CRRT and Beta-blocker InTerventions in Patients with ECMO) study is a factorial designed RCT with the purpose to test the benefit of early CRRT and beta-blocker in patients treated with V-A ECMO. In the CRRT arm, patients will be randomized to simultaneous CRRT (not late than 24 hours after the initiation of ECMO) or routine therapy (CRRT when indicated). In the beta-blocker arm, patients will be randomized to beta-blocker treatment with a heart rate target of 75±5 bpm or routine therapy. The primary outcome is all-cause mortality at 30 days. Patients discharged alive will be followed for 1 year. Data of mortality and quality of life which are secondary outcomes of this study, will be collected.

Conditions

Cardiogenic Shock

Keywords

extracorporeal membrane oxygenation; renal replacement therapy; beta-blocker

Outcome Measures

Primary Outcomes (1)

• All-cause mortality

  30 days

Secondary Outcomes (8)

• All-cause mortality

  365 days

• Proportion of patients receiving long-term RRT

  365 days/when patient dies

• Success rate of weaning from ECMO

  30 days

• Any serious adverse events (SAEs)

  30 days

• EQ-5D score

  365 days

Study Arms (4)

Simultaneous CRRT group

EXPERIMENTAL

CRRT is initiated simultaneously (not late than 24 hours from the initiation of ECMO treatment), regardless of presentation of conventional indication of CRRT. CRRT lasts for 12 hours or more is recommended.The physician can decide when to withdraw CRRT based on the patient's condition.

Device: Simultaneous CRRT

Conventional-indication CRRT group

EXPERIMENTAL

CRRT is not initiated unless conventional indication of CRRT is presented. The conventional indication of CRRT is as follow: KDIGO stage 3 AKI and one of the following criteria is met: severe hyperkalemia (\> 6.5 mmol/L), metabolic acidosis (pH \< 7.2), pulmonary edema, blood urea nitrogen level \>112 mg/dL, or oliguria (urine output \< 200 mL/12 h) for more than 72 hours.

Device: Conventional-indication CRRT

Esmolol group

EXPERIMENTAL

Patients will receive a continuous esmolol infusion in addition to routine management. The esmolol infusion commences at 25 mg/h and increases by 25 mg/h every 20-minute until the maximal tolerate dosage is reached or the heart rate reduced to 75±5 bpm, or an upper dose limit of 2000 mg/h is reached. Continue infusing esmolol to maintain the heart rate threshold or at the discretion of the physician until either ICU discharge or death. Oral beta-blockers should be considered before the withdrawal of esmolol.

Drug: Esmolol

Control group

EXPERIMENTAL

All beta-blockers, including esmolol, should not be used during ICU treatment, unless the doctor thinks there's a strong indication.

Drug: Standard care

Interventions

Simultaneous CRRT DEVICE

The patients in the simultaneous CRRT group will receive CRRT within 24 hours after the initiation of ECMO support.

Simultaneous CRRT group

Conventional-indication CRRT DEVICE

The patients in the conventional-indication group will not receive CRRT until the patient demonstrates AKI and fulfills any one of the criteria of the conventional CRRT indication.

Conventional-indication CRRT group

Esmolol DRUG

The patients in esmolol group will receive a continuous esmolol infusion in addition to the standard care.

Esmolol group

Standard care DRUG

The patients in control group will not receive any beta-blockers, including esmolol, unless the doctor thinks there's a strong indication.

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients receiving VA-ECMO support for any reason no longer than 24 hours
• Provision of informed consent

You may not qualify if:

• Age \< 18 years
• Patients with convention indication of CRRT: AKI prior to enrollment caused by any reason, at least one of the following criteria is met: severe hyperkalemia (\> 6.5 mmol/L), metabolic acidosis (pH \< 7.2), pulmonary edema, blood urea nitrogen level \> 112 mg/dL, or oliguria (urine output \< 200 mL/12h) for more than 72 hours.
• CKD with estimated GFR\<30 mL/min
• Have already initiated CRRT
• Active hemorrhage/thrombotic thrombocytopenic purpura
• Respiratory failure has already initiated VV-ECMO or extracorporeal carbon dioxide removal device before the initiation of VA-ECMO of this time.
• Prepared for heart transplant or patients received heart transplant.
• Patients receiving VA-ECMO support for any reason.
• Dopamine/dobutamine \<5 μg/kg/min, no administration of adrenaline or norepinephrine.
• Within 7 days after initiation of VA-ECMO
• Age \< 18 years
• Contraindications or intolerance to beta-blockers
• Moderate or severe bronchial asthma attack or history of bronchial asthma
• Sinus bradycardia (heart rate \< 60 bpm)
• Type II second-degree or third-degree AVB

Sponsors & Collaborators

• Beijing Anzhen Hospital: lead
• The First Affiliated Hospital of Zhengzhou University: collaborator

Study Sites (1)

Beijing Anzhen Hospital

Beijing, 100029, China

Location

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  PMID: 35986410 DERIVED

MeSH Terms

Conditions

Shock, Cardiogenic

Interventions

esmolol; Standard of Care

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Shock

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Jianzeng Dong, PhD., Md.

  Beijing Anzhen Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Heart Failure Center

Study Record Dates

• First Submitted: May 27, 2018
• First Posted: June 8, 2018
• Study Start: December 18, 2018
• Primary Completion: October 22, 2022
• Study Completion: May 1, 2023
• Last Updated: April 24, 2024

Record last verified: 2024-04

Locations

CN (1)