Cardiogenic ShockPhase 4ELITENCT03549923
Evaluation of Early CRRT InTerventions in Patients With ECMO(ELITE)
A Phase 4 study testing Simultaneous CRRT, Conventional-indication CRRT and Esmolol in people with Cardiogenic Shock, run by Beijing Anzhen Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiogenic Shock
- What is being tested?
- Simultaneous CRRT, Conventional-indication CRRT and Esmolol
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 131 participants
- Where
- 1 siteChina
- Study dates
- 18 Dec 2018to 1 May 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients receiving VA-ECMO support for any reason no longer than 24 hours
- Provision of informed consent
- 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
Who cannot join
- 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.
Show all 17Show fewer
- Prepared for heart transplant or patients received heart transplant.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of Early CRRT Intervention in Patients Receiving VA-ECMO Support on 30-day Mortality: A Randomized Controlled Trial
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.
Read the detailed 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, 2×2 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:
- 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.
- 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 μg/kg/min, and with neither epinephrine nor norepinephrine will be randomized to the following 2 groups:
- 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.
- 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:
- All-cause mortality at 365 days
- Proportion of patients with long-term RRT indicated
- Success rate of weaning from ECMO: defined as survive > 24 hours after weaning
- 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.
- EQ-5D score at 365 days
- Duration stay at ICU and hospital.
- Unplanned readmission to hospital.
- 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.
- Conditions
- Cardiogenic Shock
- Being tested
- Simultaneous CRRT, Conventional-indication CRRT, Esmolol, Standard care
- Keywords
- extracorporeal membrane oxygenation, renal replacement therapy, beta-blocker
- Medical subject headings
- Shock, Cardiogenic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Simultaneous CRRTDevice
The patients in the simultaneous CRRT group will receive CRRT within 24 hours after the initiation of ECMO support.
Conventional-indication CRRTDevice
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.
EsmololDrug
The patients in esmolol group will receive a continuous esmolol infusion in addition to the standard care.
Standard careDrug
The patients in control group will not receive any beta-blockers, including esmolol, unless the doctor thinks there's a strong indication.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Standard care |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause mortality
Measured: 30 days
Secondary outcomes (8)
All-cause mortality
Measured: 365 days
Proportion of patients receiving long-term RRT
Measured: 365 days/when patient dies
Success rate of weaning from ECMO
Success weaning from ECMO is defined as survive > 24 hours after weaning
Measured: 30 days
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.
Measured: 30 days
EQ-5D score
Measured: 365 days
Duration stay at ICU and hospital
Measured: 365 days
Unplanned readmission to hospital
Measured: 30 days
Cause-specific mortality
Measured: 365 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2018
- Study start18 Dec 2018
- Primary completion22 Oct 2022
- Study completion1 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (27)Papers the sponsor has linked to this study.
- Other trials for Cardiogenic ShockStudies of the same condition, open and under way.
- More trials run by Beijing Anzhen HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 131 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beijing Anzhen Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jianzeng Dong, Beijing Anzhen Hospital
- Investigators
- Jianzeng Dong, PhD., Md., Principal investigator, Beijing Anzhen Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03549923
- Sponsor's protocol ID
- 2016YFC1301000
- Acronym
- ELITE
- Status last verified
- Apr 2024
- First submitted
- 27 May 2018
- Last updated
- 24 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Werdan K, Muller U, Reithmann C, Pfeifer A, Hallstrom S, Koidl B, Schlag G. Mechanisms in acute septic cardiomyopathy: evidence from isolated myocytes. Basic Res Cardiol. 1991 Sep-Oct;86(5):411-21. doi: 10.1007/BF02190709.
PubMed 1662946Aso S, Matsui H, Fushimi K, Yasunaga H. In-hospital mortality and successful weaning from venoarterial extracorporeal membrane oxygenation: analysis of 5,263 patients using a national inpatient database in Japan. Crit Care. 2016 Apr 5;20:80. doi: 10.1186/s13054-016-1261-1.
PubMed 27044572Chen H, Yu RG, Yin NN, Zhou JX. Combination of extracorporeal membrane oxygenation and continuous renal replacement therapy in critically ill patients: a systematic review. Crit Care. 2014 Dec 8;18(6):675. doi: 10.1186/s13054-014-0675-x.
PubMed 25482187Alonso de Vega JM, Diaz J, Serrano E, Carbonell LF. Oxidative stress in critically ill patients with systemic inflammatory response syndrome. Crit Care Med. 2002 Aug;30(8):1782-6. doi: 10.1097/00003246-200208000-00018.
PubMed 12163793Bohm M, Link A, Cai D, Nieminen MS, Filippatos GS, Salem R, Cohen Solal A, Huang B, Padley RJ, Kivikko M, Mebazaa A. Beneficial association of beta-blocker therapy on recovery from severe acute heart failure treatment: data from the Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support trial. Crit Care Med. 2011 May;39(5):940-4. doi: 10.1097/CCM.0b013e31820a91ed.
PubMed 21283007Rudiger A. Beta-block the septic heart. Crit Care Med. 2010 Oct;38(10 Suppl):S608-12. doi: 10.1097/CCM.0b013e3181f204ca.
PubMed 21164404Sander O, Welters ID, Foex P, Sear JW. Impact of prolonged elevated heart rate on incidence of major cardiac events in critically ill patients with a high risk of cardiac complications. Crit Care Med. 2005 Jan;33(1):81-8; discussion 241-2. doi: 10.1097/01.ccm.0000150028.64264.14.
PubMed 15644652Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016 Jul 14;37(27):2129-2200. doi: 10.1093/eurheartj/ehw128. Epub 2016 May 20. No abstract available.
PubMed 27206819Champion S, Belcour D, Vandroux D, Drouet D, Gauzere BA, Bouchet B, Bossard G, Djouhri S, Jabot J, Champion M, Lefort Y. Stress (Tako-tsubo) cardiomyopathy in critically-ill patients. Eur Heart J Acute Cardiovasc Care. 2015 Apr;4(2):189-96. doi: 10.1177/2048872614547686. Epub 2014 Sep 8.
PubMed 25202025Yan X, Jia S, Meng X, Dong P, Jia M, Wan J, Hou X. Acute kidney injury in adult postcardiotomy patients with extracorporeal membrane oxygenation: evaluation of the RIFLE classification and the Acute Kidney Injury Network criteria. Eur J Cardiothorac Surg. 2010 Feb;37(2):334-8. doi: 10.1016/j.ejcts.2009.07.004. Epub 2009 Aug 18.
PubMed 19692267Isogai T, Matsui H, Tanaka H, Fushimi K, Yasunaga H. Early beta-blocker use and in-hospital mortality in patients with Takotsubo cardiomyopathy. Heart. 2016 Jul 1;102(13):1029-35. doi: 10.1136/heartjnl-2015-308712. Epub 2016 Feb 15.
PubMed 26879240Andreis DT, Singer M. Catecholamines for inflammatory shock: a Jekyll-and-Hyde conundrum. Intensive Care Med. 2016 Sep;42(9):1387-97. doi: 10.1007/s00134-016-4249-z. Epub 2016 Feb 12.
PubMed 26873833Salvadori A, Pasquier P, Jarrassier A, Renner J, Merat S. Adverse cardiac events during catecholamine therapy: a role for hydrocortisone? Intensive Care Med. 2012 Oct;38(10):1725; author reply 1726. doi: 10.1007/s00134-012-2663-4. Epub 2012 Aug 7. No abstract available.
PubMed 22868276Schmidt M, Bailey M, Kelly J, Hodgson C, Cooper DJ, Scheinkestel C, Pellegrino V, Bellomo R, Pilcher D. Impact of fluid balance on outcome of adult patients treated with extracorporeal membrane oxygenation. Intensive Care Med. 2014 Sep;40(9):1256-66. doi: 10.1007/s00134-014-3360-2. Epub 2014 Jun 17.
PubMed 24934814Schmittinger CA, Torgersen C, Luckner G, Schroder DC, Lorenz I, Dunser MW. Adverse cardiac events during catecholamine vasopressor therapy: a prospective observational study. Intensive Care Med. 2012 Jun;38(6):950-8. doi: 10.1007/s00134-012-2531-2. Epub 2012 Apr 12.
PubMed 22527060
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Early CRRT Intervention in Patients Receiving VA-ECMO Support on 30-day Mortality: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03549923
- Acronym / sponsor ID
- ELITE / 2016YFC1301000
- Conditions
- Cardiogenic Shock
- Keywords
- extracorporeal membrane oxygenation, renal replacement therapy, beta-blocker
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 131 participants (actual)
- Lead sponsor
- Beijing Anzhen HospitalUniversity, hospital or other
- Collaborators
- The First Affiliated Hospital of Zhengzhou University
- Study start
- 18 Dec 2018 (actual)
- Primary completion
- 22 Oct 2022 (actual)
- Study completion
- 1 May 2023 (actual)
- First posted
- 8 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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, 2×2 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:
- 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.
- 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 μg/kg/min, and with neither epinephrine nor norepinephrine will be randomized to the following 2 groups:
- 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.
- 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:
- All-cause mortality at 365 days
- Proportion of patients with long-term RRT indicated
- Success rate of weaning from ECMO: defined as survive > 24 hours after weaning
- 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.
- EQ-5D score at 365 days
- Duration stay at ICU and hospital.
- Unplanned readmission to hospital.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Simultaneous CRRT group | Experimental | Device: Simultaneous CRRTCRRT 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. |
| Conventional-indication CRRT group | Experimental | Device: Conventional-indication CRRTCRRT 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. |
| Esmolol group | Experimental | Drug: EsmololPatients 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. |
| Control group | Experimental | Drug: Standard careAll beta-blockers, including esmolol, should not be used during ICU treatment, unless the doctor thinks there's a strong indication. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients receiving VA-ECMO support for any reason no longer than 24 hours
- Provision of informed consent
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Simultaneous CRRTThe patients in the simultaneous CRRT group will receive CRRT within 24 hours after the initiation of ECMO support. | Device | Simultaneous CRRT group |
| Conventional-indication CRRTThe 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. | Device | Conventional-indication CRRT group |
| EsmololThe patients in esmolol group will receive a continuous esmolol infusion in addition to the standard care. | Drug | Esmolol group |
| Standard careThe patients in control group will not receive any beta-blockers, including esmolol, unless the doctor thinks there's a strong indication. | Drug | Control group |
Primary outcome
All-cause mortality
Time frame: 30 days
8 secondary outcomes
All-cause mortality
Time frame: 365 days
Proportion of patients receiving long-term RRT
Time frame: 365 days/when patient dies
Success rate of weaning from ECMO
Time frame: 30 days
Any serious adverse events (SAEs)
Time frame: 30 days
EQ-5D score
Time frame: 365 days
Duration stay at ICU and hospital
Time frame: 365 days
Unplanned readmission to hospital
Time frame: 30 days
Cause-specific mortality
Time frame: 365 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2024.
- Background: PubMed 1662946Werdan K, Muller U, Reithmann C, Pfeifer A, Hallstrom S, Koidl B, Schlag G. Mechanisms in acute septic cardiomyopathy: evidence from isolated myocytes. Basic Res Cardiol. 1991 Sep-Oct;86(5):411-21. doi: 10.1007/BF02190709.
- Background: PubMed 27044572Aso S, Matsui H, Fushimi K, Yasunaga H. In-hospital mortality and successful weaning from venoarterial extracorporeal membrane oxygenation: analysis of 5,263 patients using a national inpatient database in Japan. Crit Care. 2016 Apr 5;20:80. doi: 10.1186/s13054-016-1261-1.
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- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jianzeng Dong, PhD., Md. principal investigator
Beijing Anzhen Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Simultaneous CRRT, Conventional-indication CRRT and Esmolol in people with Cardiogenic Shock, run by Beijing Anzhen Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All-cause mortality (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03549923, which also lists 27 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2024.