The Effect of Simultaneous Renal Replacement Therapy on Extracorporeal Membrane Oxygenation Support for Cardiogenic Shock Patients

Extracorporeal membrane oxygenation (ECMO) is a temporary mechanical circulatory support device for cardiogenic shock (CS) patients. During ECMO support, renal replacement therapy (RRT) facilitate more rapid metabolic or uremic control and more effective prevention and management of fluid overload which happened in critical state. CS patients who are likely to receive ECMO support will be enrolled and randomized with a 1:1 allocation to a simultaneous RRT arm vs. standard care arm.

1. The patients in the simultaneous RRT arm will receive RRT when ECMO is commenced.
2. The patients in the standard care arm will not receive RRT when ECMO is commenced. Only when a patient demonstrates AKI and fulfills any one of the criteria of the conventional RRT indication during ECMO support or after ECMO weaning, conventional-indication RRT would be delivered.

The primary outcome is all-cause 30-day mortality after ECMO is commenced

Study Overview

• Status: Unknown
• Conditions: Cardiogenic Shock
• Intervention / Treatment: Procedure: Simultaneous RRT; Procedure: Standard care

Detailed Description

Background:

Extracorporeal membrane oxygenation (ECMO) is a temporary mechanical circulatory support device for cardiogenic shock (CS) patients. Patients with fluid overload (FO) and sever metabolic disorder in the early phase of ECMO support exhibit higher hospital mortality. Simultaneous renal replacement therapy (RRT) is routinely used to facilitate more rapid metabolic or uremic control and more effective prevention and management of fluid overload when ECMO is commenced in some ECMO centers registered in the Extracorporeal Life Support Organization (ELSO). However, high-quality evidence to support the strategy of simultaneous RRT during ECMO support is currently lacking. The investigators aim to perform a single center, randomized, controlled trial to evaluate the impact of simultaneous RRT on outcomes during ECMO support for CS patients.

Hypotheses:

The investigators hypothesize that simultaneous RRT with ECMO will improve survival, reduce morbidity, and shorten duration on ECMO support, duration on invasive ventilation, total days of ICU stay and hospitalization, and time to recovery from electrolyte disturbance.

Design:

Prospective, single-center, randomized, open-label trial comparing simultaneous RRT and standard care strategies in terms of overall survival.

CS patients who are likely to receive ECMO support will be enrolled and randomized with a 1:1 allocation to a simultaneous RRT arm vs. standard care arm.

1. Simultaneous RRT arm: The continuous renal replacement therapy (CRRT) machine is primed and connected to the patient by a "machine in-line" CRRT access after randomization. The drainage tube of the CRRT machine is connected to the ECMO circuit where is after the membrane lung, and the return tube before the membrane lung. The simultaneous RRT begins after ECMO is commenced and finishes when a patient has been weaned from ECMO. If a patient has AKI (The definition is described in outcomes.) after ECMO weaning and fulfills any of the criteria of the following conventional indications, conventional-indication RRT should be delivered with independent CRRT access with a central venous catheter: (1) Serum potassium≥6.0 mmol/L, (2) Serum bicarbonate≤10 mmol/L, or (3) urine output < 0.5 ml/kg/h for 24 hours after ECMO weaning.
2. Standard care arm: Only when a patient demonstrates AKI and fulfills any one of the criteria of the conventional indication mentioned above during ECMO support or after ECMO weaning, conventional-indication RRT should be delivered. The "machine in-line" CRRT access or independent CRRT access is separately used when RRT is delivered during ECMO support or after ECMO weaning.

Primary outcome:

All-cause 30-day mortality after ECMO is commenced.

Secondary outcomes:

Morbidity (acute kidney injury, infection), duration on ECMO support, duration on invasive ventilation, total days of ICU stay and hospitalization, and time to recovery from electrolyte disturbance.

Number of subjects required:

The baseline hospital mortality (66%) of CS patients with ECMO support was obtained from the investigators' previous study. Based on their literature research, early initiation of RRT could reduce the mortality by 18%. Assuming all-cause 30-day mortalities in the control and intervention groups of 66% and 48%, respectively, with a two-sided significance of 0.05 and a power of 0.8, a total of 262 patients (131 for each arm) will be required, including an estimated dropout rate of 10%.

• Study Type: Interventional
• Enrollment (Anticipated): 262
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaotong Hou, PhD., MD.; Phone Number: 86 18911662932; Email: xt.hou@ccmu.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100029
      • Recruiting
      • Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University
      • Contact: Xiaotong Hou, PhD., MD.; Phone Number: 86 18911662932; Email: xt.hou@ccmu.edu.cn
      • Principal Investigator: Xiaotong Hou, PhD., MD.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 and ≤ 70 years.
2. Admission to ICU.
3. Criteria for the diagnosis of CS as follows: (1) systolic blood pressure less than 90 mmHg for 30 min, a mean arterial pressure less than 65 mmHg for 30 min, or vasopressors required to achieve a blood pressure ≥ 90 mmHg; (2) pulmonary congestion or elevated left-ventricular filling pressures; and (3) signs of impaired organ perfusion with at least one of the following criteria: (a) altered mental status; (b) cold, clammy skin; (c) oliguria; and (d) increased serum lactate.
4. ECMO will supply cardiopulmonary support to the patient.

Exclusion Criteria:

1. Refusal of consent.
2. Received or decided to receive RRT before ECMO was commenced.
3. Fulfilled the criteria for Chronic Kidney Disease (either of the following present for >3 months): (1) Albuminuria (albumin excretion rate > 30 mg/24 hours; albumin-to-creatinine ratio > 30 mg/g); (2) urine sediment abnormalities; (3) electrolyte and other abnormalities due to tubular disorders; (4) abnormalities detected by histology; (5) structural abnormalities detected by imaging; and (6) history of kidney transplantation.
4. Received ECMO bridging to a long-term ventricle assist device or heart transplantation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Simultaneous RRT; The patients in the simultaneous RRT arm will receive RRT when ECMO is commenced.	Procedure: Simultaneous RRT; The patients in the simultaneous RRT arm will receive RRT when ECMO is commenced. (see Study Description)
Experimental: Standard care; The patients in the standard care arm will not receive RRT when ECMO is commenced. Only when a patient demonstrates AKI and fulfills any one of the criteria of the conventional RRT indication, RRT would be delivered.	Procedure: Standard care; The patients in the standard care arm will not receive RRT when ECMO is commenced. Only when a patient demonstrates AKI and fulfills any one of the criteria of the conventional RRT indication, RRT would be delivered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
All-cause mortality	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of successful weaning from ECMO		30 days
ICU length of stay		60 days
Hospital length of stay		60 days
Rate of acute kidney injury	AKI is defined as any of the following: (1) increase in serum creatinine (SCr) by ≥ 26.5lmol/l in 48 hours; (2) increase in SCr to ≥ 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or (3) urine output < 0.5 ml/kg/h for 6 hours (urine output is only assessed when the CRRT machine is absent or with a fluid removal rate of 0 ml/h).	30 days
Rate of infection	Any kinds of infection	30 days
Duration on ECMO support		60 days
Duration on invasive ventilation		60 days
Time to recovery from electrolyte and metabolic disturbance		30 days

Collaborators and Investigators

• Sponsor: Beijing Anzhen Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Anticipated): September 1, 2019
• Study Completion (Anticipated): September 1, 2019

Study Registration Dates

• First Submitted: August 8, 2016
• First Submitted That Met QC Criteria: August 16, 2016
• First Posted (Estimate): August 17, 2016

Study Record Updates

• Last Update Posted (Actual): January 23, 2019
• Last Update Submitted That Met QC Criteria: January 22, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Renal Replacement Therapy; Cardiogenic Shock; Extracorporeal Membrane Oxygenation
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Shock; Shock, Cardiogenic
• Other Study ID Numbers: Z161100000516017

Plan for Individual participant data (IPD)

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

Study Data/Documents

1. Study Protocol
   Information comments: Additional file of study protocol