PGE1 as Additive Anticoagulant in ECMO-Therapy

Phase 2TerminatedNCT02895373

Thomas Staudinger50 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Respiratory Distress Syndrome, Adult Extracorporeal Membrane Oxygenation

Interventions

AlprostadilDRUG

5ng/kg/min, continuously, start within 24h of initiation of ECMO therapy and end at the end of ECMO therapy

0.9% sodium chloride solutionDRUG

continuously, start within 24h of initiation of ECMO therapy and end at the end of ECMO therapy

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Medical University of Vienna, Department of Medicine I, Intensive Care Unit

Vienna, Austria

Outcomes

Primary Outcomes

Bleeding rate (quantified by the number of packed red blood cells transfused in relation to the duration of ECMO therapy)

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.

Time frame: up to 6 months

Secondary Outcomes

number of bleeding incidences and severity of bleeding (bleeding grades)

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

Time frame: up to six months

Number of Clotting Events

* 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.

Time frame: up to six months

Function of the membrane oxygenator

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.

Time frame: up to six months

Number of changes of the membrane oxygenator relative to the duration of ECMO therapy

Membrane oxygenators need to be changed due to loss of function (cause by clotting etc.).

Time frame: up to six months

Data from ClinicalTrials.gov

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