PGE1 as Additive Anticoagulant in ECMO-Therapy

Respiratory Distress Syndrome, Adult Clinical Trial

— ECMO_PGE1  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02895373
• Other study ID #: ECMO_PGE1_2.1
• Status: Terminated
• Phase: Phase 2
• Start date: July 2016
• Est. completion date: July 2021

Study information

• Verified date: January 2022
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 50
• Est. completion date: July 2021
• Est. primary completion date: May 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Extracorporeal Membrane Oxygenation
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn

Intervention

Drug:
• Alprostadil
5ng/kg/min, continuously, start within 24h of initiation of ECMO therapy and end at the end of ECMO therapy
• 0.9% sodium chloride solution
continuously, start within 24h of initiation of ECMO therapy and end at the end of ECMO therapy

Locations

Country	Name	City	State
Austria	Medical University of Vienna, Department of Medicine I, Intensive Care Unit	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Thomas Staudinger

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	up to 6 months
Secondary	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	up to six months
Secondary	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.	up to six months
Secondary	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.	up to six months
Secondary	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.).	up to six months
Secondary	Inflammation specific biomarkers (i.e. C-reactive protein, blood counts, reticulated platelets, etc.)	daily routine measurements and frozen plasma	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Catecholamines	need for and dose of 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
Secondary	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
Secondary	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
Secondary	mortality	by chart review or telephone call	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
Secondary	number of platelet transfusions, fresh frozen plamsa, coagulation interventions etc.	by chart review, number relative to the duration of ECMO therapy	up to six months
Secondary	number of platelet transfusions	by chart review, number relative to the duration of ECMO therapy	up to six months
Secondary	number of coagulation interventions	by chart review, number relative to the duration of ECMO therapy	up to six months