PGE1 as Additive Anticoagulant in ECMO-Therapy (ECMO_PGE1)

Thomas Staudinger

Status and phase: Terminated; Phase 2

Conditions: Respiratory Distress Syndrome, Adult; Extracorporeal Membrane Oxygenation

Treatments: Drug: Alprostadil; Drug: 0.9% sodium chloride solution

Study type: Interventional

Funder types: Other

Identifiers

NCT02895373

ECMO_PGE1_2.1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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50 participants in 2 patient groups, including a placebo group

Alprostadil

Experimental group

Description:

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

Treatment:

Drug: Alprostadil

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: 0.9% sodium chloride solution