Anticoagulants and Bleeding Disorders, Extracorporeal Membrane Oxygenation Complication
Conditions
Brief summary
This prospective, randomized, controlled pilot trial aims to assess the safety and feasibility of Argatroban as an alternative anticoagulant to unfractionated heparin in patients receiving extracorporeal membrane oxygenation.
Interventions
DRUGArgatroban
Argatroban is a synthetic, univalent DTI, that directly binds to the catalytic thrombin binding site exerting its effects
DRUGUnfractionated heparin
Unfractionated heparin produces its major anticoagulant effect by inactivating thrombin and activated factor X (factor Xa) through an antithrombin (AT)-dependent mechanism.
Sponsors
Medical University of Vienna
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomization ratio of 1:1 for anticoagulation with Argatroban or Unfractionated Heparin
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Minimum Age 18 years * VV- or VA-ECMO therapy * Minimum of 24h planned ECMO-therapy
Exclusion criteria
* History of Heparin-induced thrombocytopenia (HIT) * High risk of bleeding, contraindication for anticoagulation (eg. active GI-bleeding, Intracerebral bleeding; Platelet count \<50G/l, congenital bleeding disorder) * Pregnancy * Severe Liver disease (SOFA score liver domain 4 points = Bilirubin \>12mg/dl) * Postoperative admission * Strong lupus anticoagulant or acquired intrinsic clotting factor deficiency at admission (APTT \>50 sec without anticoagulation).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bleeding and thrombosis with Argatroban compared to unfractionated Heparin (UFH) | From date of randomization until the date of ECMO discontinuation, or death, whichever came first, assessed up to 120 days | Bleeding will be assessed continuously by the investigators according to the BARC bleeding classification, where bleeding type 2 or higher will be considered as clinically significant bleeding; outcome measures will be the incidence of clinically significant bleeding per ECMO day and time to first bleeding; thrombosis is defined as any occurence of thromboembolism including membrane lung exchange due to suspected thrombosis, pulmonary embolism or deep vein thrombosis; outcome measures will be the incidence of thromboembolism per ECMO day and the time to first thromboembolism |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| study enrollment, study completion and ability to achieve target values of Argatroban as anticoagulant in ECMO | From date of randomization until the date of ECMO discontinuation, or death, whichever came first, assessed up to 120 days | ratio of screened to included patients, proportion of patients who completed the study according to the protocol, proportion of coagulation tests within range and total number of dose adjustments |
Other
| Measure | Time frame | Description |
|---|---|---|
| Transfusion rate of packed red blood cells assessed as total units/ECMO day | From date of randomization until the date of ECMO discontinuation, or death, whichever came first, assessed up to 120 days | Assessment of the total amount of units (250-300ml each) packed red blood cells transfused per ECMO day following a transfusion threshold of Hb\<8g/dl |
| Grading of bleeding | From date of randomization until the date of ECMO discontinuation, or death, whichever came first, assessed up to 120 days | According to the Bleeding Academic Research Consortium type 1 - 5 (Type 1: Bleeding that is not actionable; Type 2: Any clinically overt sign of hemorrhage that is actionable and requires diagnostic studies, hospitalization, or treatment by a health care professional; Type 3a. Overt bleeding plus hemoglobin drop of 3 to \< 5 g/dL (provided hemoglobin drop is related to bleed); transfusion with overt bleeding; Type 3b. Overt bleeding plus hemoglobin drop \< 5 g/dL (provided hemoglobin drop is related to bleed); cardiac tamponade; bleeding requiring surgical intervention for control; bleeding requiring IV vasoactive agents; type 3c. Intracranial hemorrhage confirmed by autopsy, imaging, or lumbar puncture; intraocular bleed compromising vision; Type 4: CABG-related bleeding within 48 hours; Type 5a. Probable fatal bleeding; Type 5b. Definite fatal bleeding (overt or autopsy or imaging confirmation) |
| Mortality rate at day 28/90 | Until 90 days after start of study drug administration | assessed by chart review or telephone call |
Countries
Austria
Outcome results
None listed