ECMO_PGE1: PGE1 as Additive Anticoagulant in ECMO-Therapy
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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 |
Drug: Alprostadil
5ng/kg/min, continuously, start within 24h of initiation of ECMO therapy and end at the end of ECMO therapy
|
| Placebo Comparator: Placebo 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 |
Drug: 0.9% sodium chloride solution
continuously, start within 24h of initiation of ECMO therapy and end at the end of ECMO therapy
|
Outcome Measures
Primary Outcome Measures
- 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
- 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 therapy
- Number 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.
- 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]
- 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]
- 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]
- 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]
- 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
- 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]
- 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
- 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 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
minimum age 18 years
-
Veno-Venous- ECMO
-
Minimum of 24h planned ECMO- therapy
Exclusion Criteria:
-
• 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Medical University of Vienna, Department of Medicine I, Intensive Care Unit | Vienna | Austria | 1090 |
Sponsors and Collaborators
- Thomas Staudinger
Investigators
- Principal Investigator: Thomas Staudinger, MD, Medical University of Vienna
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ECMO_PGE1_2.1