Clinical trial NCT02895373: PGE1 as Additive Anticoagulant in ECMO-Therapy
Official title: A Prospective Randomized, Double Blind Study on Safety and Efficacy of Alprostadil as Additional Anticoagulant in Patients With Veno- Venous Extracorporeal Membrane Oxygenation (ECMO)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Respiratory Distress Syndrome, Adult
Extracorporeal Membrane Oxygenation
Keywords: platelet inhibition
alprostadil
extracorporeal membrane oxygenation
bleeding
thromboembolic
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2016-09-09
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Bleeding rate (quantified by the number of packed red blood cells transfused in relation to the duration of ECMO therapy)
timeFrame: up to 6 months
Secondary outcomes:
measure: number of bleeding incidences and severity of bleeding (bleeding grades)
timeFrame: up to six months
measure: Number of Clotting Events
timeFrame: up to six months
measure: Function of the membrane oxygenator
timeFrame: up to six months
measure: Number of changes of the membrane oxygenator relative to the duration of ECMO therapy
timeFrame: up to six months
measure: Inflammation specific biomarkers (i.e. C-reactive protein, blood counts, reticulated platelets, etc.)
timeFrame: 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
measure: Global Coagulation assays
timeFrame: 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
measure: Thromboelastometry
timeFrame: 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
measure: platelet function analyzer-100
timeFrame: 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
measure: Fibrinogen levels
timeFrame: 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
measure: whole blood aggregometry
timeFrame: 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
measure: D-Dimer levels
timeFrame: 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
measure: Catecholamines
timeFrame: 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
measure: cardiac output
timeFrame: 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
measure: blood pressure
timeFrame: 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
measure: mortality
timeFrame: 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
measure: number of platelet transfusions, fresh frozen plamsa, coagulation interventions etc.
timeFrame: up to six months
measure: number of platelet transfusions
timeFrame: up to six months
measure: number of coagulation interventions
timeFrame: up to six months
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna, Department of Medicine I, Intensive Care Unit
Study officials:
affiliation: Medical University of Vienna
name: Thomas Staudinger, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Buchtele N, Schorgenhofer C, Schwameis M, Jilma B, Schellongowski P, Herkner H, Riss K, Schmid M, Hermann A, Robak O, Nagler B, Traby L, Bojic A, Staudinger T. Add-On Prostaglandin E1 in Venovenous Extracorporeal Membrane Oxygenation: A Randomized, Double-Blind, Placebo-controlled Pilot Trial. Am J Respir Crit Care Med. 2022 Jul 15;206(2):170-177. doi: 10.1164/rccm.202110-2359OC.