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

  • STATUS
    Recruiting
  • End date
    Apr 23, 2022
  • participants needed
    550
  • sponsor
    Beijing Anzhen Hospital
Updated on 23 January 2021

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 755 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.

Description

Background

Extracorporeal membrane oxygenation (ECMO) is of great value in supporting patients with severe cardiopulmonary failure, but the mortality rate is still high.

Acute kidney injury (AKI) and fluid overload (FO) are the leading causes of death in patients under Veno-arterial (VA) ECMO. Continuous renal replacement therapy (CRRT) is an effective way to remove toxic substances and provide fluid management. According to current guidelines, CRRT is withhold until 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. However, fluid overload and metabolic disorders may cause irreversible damage to the patient and therefore increase mortality. The hypothesis of ELITE study is that simultaneous CRRT may provide better fluid management and avoid metabolic disorders, and bring survival benefit in VA-ECMO patients.

Patients under VA-ECMO are critically ill with high plasma catecholamine levels and treatment of various inotropic agents, which are toxic to the failed myocardium. Beta-blockers can antagonize the effects of endogenous and exogenous catecholamines. The hypothesis of ELITE study is that beta-blocker may protect the failing heart function and reduce 30-day mortality.

Study design:

ELITE study is a prospective, multi-centered, open, 22 factorial randomized controlled clinical trial.

In the simultaneous CRRT versus conventional-indication CRRT arm, patients under VA-ECMO will be randomized to the following 2 groups:

  1. 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.
  2. 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.

In the Beta-blocker versus routine therapy arm, patients with a maintaining dosage of dopamine/dobutamine <5 g/kg/min, and with neither epinephrine nor norepinephrine will be randomized to the following 2 groups:

  1. 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 755 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.
  2. Control group: All beta-blockers, including esmolol, should not be used during ICU treatment, unless the doctor thinks there's a strong indication.

Primary outcome: All-cause mortality at 30 days.

Secondary outcomes:

  1. All-cause mortality at 365 days
  2. Proportion of patients with long-term RRT indicated
  3. Success rate of weaning from ECMO: defined as survive > 24 hours after weaning
  4. Any serious adverse events (SAEs), 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 at 365 days
  6. Duration stay at ICU and hospital.
  7. Unplanned readmission to hospital.
  8. Cause-specific mortality

Sample size consideration:

The sample size calculations are based on the following hypothesis: (a) an estimate 30-day mortality of 70% in the control group; (b) a 20% relative risk reduction for each intervention alone (simultaneous CRRT and beta-blocker); (c) no loss to follow-up; (d) no interaction of the two interventions.

For each intervention, we calculated that a sample size of 496 patients would be required, 248 patients for the treatment group and 248 patients for the control group. In the 2 2 factorial design, patients will be randomized to one of four arms, the sample size of each would be 124 patients. With a crossover rate of 10%, the study will randomize 548 patients, 137 patients per arm.

Details
Condition Cardiogenic shock
Treatment Standard Care, Esmolol, Simultaneous CRRT, Conventional-indication CRRT
Clinical Study IdentifierNCT03549923
SponsorBeijing Anzhen Hospital
Last Modified on23 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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

Exclusion Criteria

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
Allergy to esmolol
For women at child bearing age, pregnant or positive pregnancy test
Respiratory failure has already initiated VV-ECMO or extracorporeal carbon dioxide removal device before the initiation of VA-ECMO of this time
Have been on beta-blocker treatment after initiation of ECMO
Prepared for heart transplant or patients received heart transplant
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

0/250
Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note