RATE: Reduced anticoagulation targets in extracorporeal life support

2023-509675-16-01 Therapeutic confirmatory (Phase III) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 7 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Authorised, recruitment pending
Participants planned 330
Countries 1
Sites 7

All patients who receive ECMO treatment during the study period in one the participating centers from which (deferred) informed consent is obtained. Patients in whom the ECMO is only used to bridge a procedure like a high risk percutaneous coronary intervention or during surgery are excluded.

Our primary research question is if anticoagulation with UFH with reduced anticoagulation targets or anticoagulation with low molecular weight heparin (LMWH) leads to a reduction in the occurrence of major bleeding without an increase in thromboembolic complications or a negative effect on outcome compared to the stand…

Key facts

Sponsor
Universitair Medisch Centrum Groningen
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Cardiovascular Diseases [C14]
Decision date (initial)
2025-01-28
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No

External identifiers

EU CT number
2023-509675-16-01
EudraCT number
2019-004125-24
ClinicalTrials.gov
NCT00412524

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy

Our primary research question is if anticoagulation with UFH with reduced anticoagulation targets or anticoagulation with low molecular weight heparin (LMWH) leads to a reduction in the occurrence of major bleeding without an increase in thromboembolic complications or a negative effect on outcome compared to the standard practice of high anticoagulation targets with UFH. We expect fewer complications and improvement of survival after ECMO therapy for both interventions.

Conditions and MedDRA coding

All patients who receive ECMO treatment during the study period in one the participating centers from which (deferred) informed consent is obtained. Patients in whom the ECMO is only used to bridge a procedure like a high risk percutaneous coronary intervention or during surgery are excluded.

Regulatory references

Plan to share IPD
No
EU CT numberTitleSponsor
2023-509675-16-00 Reduced anticoagulation targets in extracorporeal life support Universitair Medisch Centrum Groningen

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

  1. All adults receiving ECMO treatment at the ICU of one of the participating centers during the study period are eligible for inclusion.

Exclusion criteria 1

  1. The exclusion criteria are as follows: (1) patients in whom the ECMO is only used to bridge a procedure like a high-risk percutaneous coronary intervention or during surgery; (2) no (deferred) informed consent; (3) vital indication for robust anticoagulation (e.g., mechanic mitral valve, pulmonary embolism, a clot in the cardiac ventricle); and (4) a history of heparin-induced thrombocytopenia (HIT).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. The primary outcome parameter is a combined endpoint consisting of: 1) major bleeding including hemorrhagic stroke according to the ELSO definitions; 2) severe thromboembolic complication defined as ischemic stroke, limb ischemia (not related with distal perfusion catheter), or acute pump failure with emergency exchange; 3) mortality at 6 months.

Secondary endpoints 1

  1. Secondary outcome parameters are: 1) blood transfusions; 2) health related quality of life (HR-QoL) at 6 months; 3) exchange of the membrane oxygenator; 4) vessel thrombosis after ECMO removal detected by echography; 5) pulmonary embolism; 6) costs; 7) the individual components of the composite outcome; and 8) all thromboembolic complications combined.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Heparin

SCP100373670 · ATC

Active substance
Heparin
Substance synonyms
HEPARIINI, HEPARINUM
Route of administration
INTRAVENOUS
Max daily dose
600 IU/Kg iu/kilogram
Max total dose
109500 IU/Kg iu/kilogram
Max treatment duration
52 Week(s)
Authorisation status
Authorised
ATC code
B01AB01 — HEPARIN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Nadroparin Calcium

SCP101882242 · ATC

Active substance
Nadroparin Calcium
Route of administration
SUBCUTANEOUS INJECTION
Max daily dose
192 IU/Kg iu/kilogram
Max total dose
35040 IU/Kg iu/kilogram
Max treatment duration
52 Week(s)
Authorisation status
Authorised
ATC code
B01AB06 — NADROPARIN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Groningen

Sponsor organisation
Universitair Medisch Centrum Groningen
Address
Hanzeplein 1
City
Groningen
Postcode
9713 GZ
Country
Netherlands

Scientific contact point

Organisation
Universitair Medisch Centrum Groningen
Contact name
Walter M. van den Bergh

Public contact point

Organisation
Universitair Medisch Centrum Groningen
Contact name
Olivier van Minnen

Locations

1 EU/EEA country · 7 investigational sites

By country

CountryMS statusPlanned subjectsSites
Netherlands Authorised, recruitment pending 330 7
Rest of world 0

Investigational sites

Netherlands

7 sites · Authorised, recruitment pending
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Intensive Care, Dr. Molewaterplein 60, 3015 GJ, Rotterdam
Amsterdam UMC
Intensive Care, De Boelelaan 1117, 1081 HV, Amsterdam
Leids Universitair Medisch Centrum (LUMC)
Intensive Care, Albinusdreef 2, 2333 ZA, Leiden
University Hospital Maastricht
Intensive Care, P Debyelaan 25, 6229 HX, Maastricht
Isala Klinieken Stichting
Intensive Care, Dokter Van Heesweg 2, 8025 AB, Zwolle
Universitair Medisch Centrum Groningen
Critical Care, Hanzeplein 1, 9713 GZ, Groningen
OLVG Stichting
Intensive Care, Oosterpark 9, 1091 AC, Amsterdam

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) 2023-509675-16-01 Protocol-RATE FINAL 1.2
Recruitment arrangements (for publication) Recruitment procedure and first act of recruitment 1
Subject information and informed consent form (for publication) E1 en E2 PIF pat na IC wett vert RATE v13 1.3
Subject information and informed consent form (for publication) E1 en E2 PIF wett vert RATE v13 1.3
Summary of Product Characteristics (SmPC) (for publication) D2 SmPC heparine 1
Summary of Product Characteristics (SmPC) (for publication) D2 SmPC nadroparine 1
Synopsis of the protocol (for publication) Summary RATE protocol 1

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2025-01-27 Netherlands Acceptable with conditions
2025-01-28
2025-01-28