Reduced Anticoagulation Targets in ECLS (RATE)

NCT04536272 | Completed Phase 3 DMC

• 4 other identifiers: 20190065984801801479692019-004125-24
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 8

Brief Summary

The objective of the RATE-trial is to study if reduced anticoagulation targets during ECLS diminish bleeding complications without an increase in thromboembolic complications or a negative impact on outcome.

Conditions

Heart Failure; Respiratory Failure; Extracorporeal Membrane Oxygenation; Bleeding; Thrombosis

Keywords

Extracorporeal membrane oxygenation; Extracorporeal life support; ECMO; ECLS; Anticoagulation; Complications

Outcome Measures

Primary Outcomes (3)

• Hemorrhagic complications

  Severe hemorrhagic complications will be registered according to the Extracorporeal Life Support Organization (ELSO) definitions for major bleeding and is defined as clinically overt bleeding with a decrease in hemoglobin of at least 1,24 mmol/L (2 g/dl)/24 hours, or a transfusion requirement of ≥ 3 EH RBC over that same time period. Bleeding that is retroperitoneal, pulmonary or involves the central nervous system, or bleeding that requires surgical intervention is also considered major bleeding.

  Through ECLS completion, an average of 14 days

• Severe thromboembolic complications

  Severe thromboembolic complication defined as ischemic stroke, limb ischemia, or acute pump failure

  Through ECLS completion, an average of 14 days

• Mortality

  Mortality at 6 months

  6 months after ECLS

Secondary Outcomes (7)

• Number of blood transfusions

  Through ECLS completion, an average of 14 days

• Quality of life at 6 months

  6 months after ECLS

• Exchange of the membrane oxygenator

  Through ECLS completion, an average of 14 days

• Vessel thrombosis after ECLS removal

  After ECLS completion, an average of 14 days

• Cost- effectiveness

  6 months after ECLS

Study Arms (3)

Target of 2-2.5 times baseline aPTT (usual care, about 60-75)

ACTIVE COMPARATOR

Administration of heparin during ECLS with an aPTT target of 2-2.5 times baseline.

Drug: Heparin

Target of 1.5-2.0 times baseline aPTT (45-60 sec.)

ACTIVE COMPARATOR

Administration of heparin during ECLS with an aPTT target of 1.5-2.0 times baseline.

Drug: Heparin

LMWH guided by weight and renal function.

ACTIVE COMPARATOR

Administration of LMWH guided by weight and renal function during ECLS.

Drug: LMWH

Interventions

Heparin DRUG

Administration of heparin with a target of 2-2.5 or 1.5-2.0 times baseline aPTT during ECLS.

Also known as: Unfractionated heparin

Target of 1.5-2.0 times baseline aPTT (45-60 sec.); Target of 2-2.5 times baseline aPTT (usual care, about 60-75)

LMWH DRUG

Administration of LMWH guided by weight and renal function during ECLS.

Also known as: Dalteparine, Enoxaparine, Nadroparine, Tinzaparine

LMWH guided by weight and renal function.

Eligibility Criteria

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

You may qualify if:

• ECMO treatment during the study period in one of the participating centers
• Age above 18 years
• Written informed consent

You may not qualify if:

• Patients in whom the ECMO is only used to bridge a procedure
• Vital indication for robust anticoagulation (e.g. mechanic valve, pulmonary embolism)
• History of heparin induced thrombocytopenia

Sponsors & Collaborators

• University Medical Center Groningen: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator
• Erasmus Medical Center: collaborator
• Leiden University Medical Center: collaborator
• St. Antonius Hospital: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• Isala: collaborator
• OLVG: collaborator
• Radboud University Medical Center: collaborator

Study Sites (8)

Radboud UMC

Nijmegen, Gelderland, 6525GA, Netherlands

Location

Maastricht Universitair Medisch Centrum+

Maastricht, Limburg, 6229HX, Netherlands

Location

OLVG, location East

Amsterdam, North Holland, 1091AC, Netherlands

Location

Amsterdam UMC, location AMC

Amsterdam, North Holland, 1100DD, Netherlands

Location

Isala Clinics

Zwolle, Overijssel, 8025AB, Netherlands

Location

University Medical Center Groningen

Groningen, Provincie Groningen, 9700RB, Netherlands

Location

Leids Universitair Medisch Centrum

Leiden, South Holland, 2300RC, Netherlands

Location

Erasmus MC

Rotterdam, South Holland, 3000CA, Netherlands

Location

Related Publications (2)

• van Minnen O, Linde M, Oude Lansink-Hartgring A, van den Boogaard B, Bunge JJH, Delnoij TSR, Elzo Kraemer CV, Kuijpers M, Maas JJ, de Metz J, van de Poll M, Dos Reis Miranda D, Vlaar APJ, van Ravenzwaaij D, van den Bergh WM. Reduced anticoagulation targets in extracorporeal life support (RATE): protocol for a pre-planned secondary Bayesian analysis of the rate trial. Trials. 2025 Mar 15;26(1):90. doi: 10.1186/s13063-025-08737-6.

  PMID: 40087802 DERIVED

• van Minnen O, Oude Lansink-Hartgring A, van den Boogaard B, van den Brule J, Bulpa P, Bunge JJH, Delnoij TSR, Elzo Kraemer CV, Kuijpers M, Lambermont B, Maas JJ, de Metz J, Michaux I, van de Pol I, van de Poll M, Raasveld SJ, Raes M, Dos Reis Miranda D, Scholten E, Simonet O, Taccone FS, Vallot F, Vlaar APJ, van den Bergh WM. Reduced anticoagulation targets in extracorporeal life support (RATE): study protocol for a randomized controlled trial. Trials. 2022 May 16;23(1):405. doi: 10.1186/s13063-022-06367-w.

  PMID: 35578271 DERIVED

MeSH Terms

Conditions

Heart Failure; Respiratory Insufficiency; Hemorrhage; Thrombosis

Interventions

Heparin; Heparin, Low-Molecular-Weight; Enoxaparin; Nadroparin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Embolism and Thrombosis; Vascular Diseases

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• W.M. van den Bergh, PhD, MD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: Randomization between anticoagulation targets during ECLS of: 1). 2-2.5 times baseline aPTT (usual care, about 60-75 sec.), 2). 1.5-2.0 times baseline aPTT (45-60 sec.) or 3). LMWH guided by weight and renal function.

Study Record Dates

• First Submitted: August 24, 2020
• First Posted: September 2, 2020
• Study Start: October 1, 2020
• Primary Completion: March 7, 2025
• Study Completion: March 7, 2025
• Last Updated: May 2, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: * Researchers who provide a methodologically sound proposal which is approved by an independent review panel. * To achieve aims in the approved proposal. * Proposals should be directed to w.m.van.den.bergh@umcg.nl, requestors will need to sign a data access agreement.

Locations

NL (8)