PGE1 as Additive Anticoagulant in ECMO-Therapy
- Conditions
- Respiratory Distress Syndrome, AdultExtracorporeal Membrane Oxygenation
- Interventions
- Registration Number
- NCT02895373
- Lead Sponsor
- Thomas Staudinger
- Brief Summary
Bleeding complications and thromboembolic complications are frequent during extracorporeal membrane oxygenation (ECMO). Retrospective data suggest that platelet inhibition using prostaglandins, in this case PGE1, may reduce thromboembolic complications without increasing the bleeding risk. This randomized, double-blind trial aims to investigate the effects of PGE1 on bleeding risk, thromboembolic complications and the function of the ECMO.
- Detailed Description
Prostaglandins may inhibit platelet activation via the P2Y1 ADP receptor. Platelets may contribute to thromboembolic complications and coagulation activation during ECMO therapy. Retrospective data suggest that treatment with PGE1 may serve beneficial by reducing the amount of heparin needed for inhibition of coagulation activation, and by reducing the thromboembolic risk without increasing the risk of bleeding.
Inhibition of platelets via PGE1 (Alprostadil) may be interesting in this setting, because, in contrast to other platelet inhibitors, it has a very short half-life and platelets remain susceptible for activation by more potent agonists (i.e. thrombin, ADP). Thus, although reducing the contribution of platelets to coagulation activation, it may not affect safety of participating subjects.
This randomized, double-blind, placebo controlled trial will investigate whether treatment of patients with ECMO therapy proves beneficial.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 50
-
minimum age 18 years
- Veno-Venous- ECMO
- Minimum of 24h planned ECMO- therapy
-
• Long- term therapy with other antiplatelet drugs including Acetyl Salicylic Acid
- known Heparin induced thrombocytopenia
- Bleeding diathesis = contraindication for heparin (e.g. GI-bleeding, Intracerebral bleeding)
- Platelets < 50 G/L
- Thromboplastin time < 50%
- Pregnancy
- Patient < 18 years
- prothrombin time <50%
Drop out criteria:
- Major bleeding (from Type 3 bleeding; see "primary objective")
- Occurrence of HIT (4 T- Score: Number of platelets, development over time, manifestation of thrombosis, other reasons for thrombocytopenia [10])
- Plt < 50 G/l
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Alprostadil Alprostadil heparin (dose adjusted to aptt 50-60s) + Alprostadil (=PGE1) 5ng/kg/min, continuously, start within 24h of initiation of ECMO therapy and end at the end of ECMO therapy Placebo 0.9% sodium chloride solution heparin (dose adjusted to aptt 50-60s) + 0.9% sodium chloride infusion, continuously, start within 24h of initiation of ECMO therapy and end at the end of ECMO therapy
- Primary Outcome Measures
Name Time Method Bleeding rate (quantified by the number of packed red blood cells transfused in relation to the duration of ECMO therapy) up to 6 months The bleeding rate will be quantified by the number of packed red blood cells in relation to the duration of ECMO therapy. This duration may vary and cannot be predicted. Thus, we will calculate the required number of packed red blood cells i.e. per week.
- Secondary Outcome Measures
Name Time Method number of bleeding incidences and severity of bleeding (bleeding grades) up to six months type 0: no bleeding type1: bleeding that is not actionable type 2: any overt actionable sign of hemorrhage type3: a) overt bleeding plut hb drop of 3-5g/dl b) \>5g/dl, cardiac tamponade, requiring surgical intervention, bleeding requiring vasoactive agents c)intracranial bleeding, type 5: fatal bleeding
number and severity of bleeding relative to the duration of ECMO therapyNumber of Clotting Events up to six months * clinically noticeable thromboembolic events
* cannulized veins (Duplex 24h after canula removal)
* need of Membrane- changes,, macroscopic thrombus, discoloration
* Global clotting tests (prothrombin time, activated partial thromboplastin time, Fibrinogen, D-Dimer)
number of Clotting events in relation to the duration of ECMO therapy.Function of the membrane oxygenator up to six months The function of the membrane oxygenator will be assessed on a daily basis as part of clinical routine.This includes the capacity of oxygen transfer and carbon-dioxide (CO2) transfer.
Thromboelastometry Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months platelet function analyzer-100 Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months number of platelet transfusions, fresh frozen plamsa, coagulation interventions etc. up to six months by chart review, number relative to the duration of ECMO therapy
Number of changes of the membrane oxygenator relative to the duration of ECMO therapy up to six months Membrane oxygenators need to be changed due to loss of function (cause by clotting etc.).
Inflammation specific biomarkers (i.e. C-reactive protein, blood counts, reticulated platelets, etc.) Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months daily routine measurements and frozen plasma
Global Coagulation assays Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months Fibrinogen levels Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months D-Dimer levels Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months Catecholamines Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months need for and dose of catecholamines
blood pressure Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months mortality Day 28/90, ICU mortality assessed at the discharge from the Intensive Care unit, this will be up to 12 months after inclusion into the study by chart review or telephone call
whole blood aggregometry Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months cardiac output Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months number of platelet transfusions up to six months by chart review, number relative to the duration of ECMO therapy
number of coagulation interventions up to six months by chart review, number relative to the duration of ECMO therapy
Trial Locations
- Locations (1)
Medical University of Vienna, Department of Medicine I, Intensive Care Unit
🇦🇹Vienna, Austria