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Evaluation of Early CRRT and Beta-blocker InTerventions in Patients With ECMO(ELITE) (ELITE)

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ClinicalTrials.gov Identifier: NCT03549923
Recruitment Status : Recruiting
First Posted : June 8, 2018
Last Update Posted : January 11, 2019
Sponsor:
Collaborator:
The First Affiliated Hospital of Zhengzhou University
Information provided by (Responsible Party):
Jianzeng Dong, Beijing Anzhen Hospital

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.


Condition or disease Intervention/treatment Phase
Cardiogenic Shock Device: Simultaneous CRRT Device: Conventional-indication CRRT Drug: Esmolol Drug: Standard care Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 550 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Impact of Early CRRT or Beta-blocker Intervention in Patients Receiving VA-ECMO Support on 30-day Mortality: A 2 × 2 Partial Factorial Randomized Controlled Trial
Actual Study Start Date : December 18, 2018
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Shock

Arm Intervention/treatment
Experimental: Simultaneous CRRT group
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
The patients in the simultaneous CRRT group will receive CRRT within 24 hours after the initiation of ECMO support.

Experimental: Conventional-indication CRRT group
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
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.

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

Experimental: Control group
All beta-blockers, including esmolol, should not be used during ICU treatment, unless the doctor thinks there's a strong indication.
Drug: Standard care
The patients in control group will not receive any beta-blockers, including esmolol, unless the doctor thinks there's a strong indication.




Primary Outcome Measures :
  1. All-cause mortality [ Time Frame: 30 days ]

Secondary Outcome Measures :
  1. All-cause mortality [ Time Frame: 365 days ]
  2. Proportion of patients receiving long-term RRT [ Time Frame: 365 days/when patient dies ]
  3. Success rate of weaning from ECMO [ Time Frame: 30 days ]
    Success weaning from ECMO is defined as survive > 24 hours after weaning

  4. Any serious adverse events (SAEs) [ Time Frame: 30 days ]
    Including bleeding, severe arrhythmias, ventilator associated pneumonia, hemorrhagic infection, surgical site infection, any reason induced limb ischemia, stroke and any adverse events that the physician regards as serious.

  5. EQ-5D score [ Time Frame: 365 days ]
  6. Duration stay at ICU and hospital [ Time Frame: 365 days ]
  7. Unplanned readmission to hospital [ Time Frame: 30 days ]
  8. Cause-specific mortality [ Time Frame: 365 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for CRRT Study:

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

Exclusion Criteria for CRRT Study:

  1. Age < 18 years
  2. 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.
  3. CKD with estimated GFR<30 mL/min
  4. Have already initiated CRRT
  5. Active hemorrhage/thrombotic thrombocytopenic purpura
  6. Respiratory failure has already initiated VV-ECMO or extracorporeal carbon dioxide removal device before the initiation of VA-ECMO of this time.
  7. Prepared for heart transplant or patients received heart transplant.

Inclusion Criteria for Beta-blocker Study:

  1. Patients receiving VA-ECMO support for any reason.
  2. Dopamine/dobutamine <5 μg/kg/min, no administration of adrenaline or norepinephrine.
  3. Within 7 days after initiation of VA-ECMO

Exclusion Criteria for Beta-blocker Study:

  1. Age < 18 years
  2. 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
    • Allergy to esmolol
  3. For women at child bearing age, pregnant or positive pregnancy test.
  4. Respiratory failure has already initiated VV-ECMO or extracorporeal carbon dioxide removal device before the initiation of VA-ECMO of this time
  5. Have been on beta-blocker treatment after initiation of ECMO
  6. Prepared for heart transplant or patients received heart transplant.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03549923


Contacts
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Contact: Jianzeng Dong, PhD., Md. 86 13911828375 jz_dong@126.com
Contact: Xiaotong Hou, PhD., Md. 86 18911662932 xt.hou@ccmu.edu.cn

Locations
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China
Beijing Anzhen Hospital Recruiting
Beijing, China, 100029
Contact: Jianzeng Dong, PhD., Md.    86 13911828375    jz_dong@126.com   
Contact: Xiaotong Hou, PhD., Md.    86 18911662932    xt.hou@ccmu.edu.cn   
Sponsors and Collaborators
Beijing Anzhen Hospital
The First Affiliated Hospital of Zhengzhou University
Investigators
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Principal Investigator: Jianzeng Dong, PhD., Md. Beijing Anzhen Hospital

Publications:

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Responsible Party: Jianzeng Dong, Director of Heart Failure Center, Beijing Anzhen Hospital
ClinicalTrials.gov Identifier: NCT03549923     History of Changes
Other Study ID Numbers: 2016YFC1301000
First Posted: June 8, 2018    Key Record Dates
Last Update Posted: January 11, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jianzeng Dong, Beijing Anzhen Hospital:
extracorporeal membrane oxygenation
renal replacement therapy
beta-blocker

Additional relevant MeSH terms:
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Shock, Cardiogenic
Myocardial Infarction
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Shock
Pathologic Processes
Adrenergic beta-Antagonists
Esmolol
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists