A Prospective Randomized, Double Blind Study on Safety and Efficacy of Alprostadil as Additional Anticoagulant in Patients With Veno- Venous Extracorporeal Membrane Oxygenation (ECMO)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Bleeding rate (quantified by the number of packed red blood cells transfused in relation to the duration of ECMO therapy)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •minimum age 18 years
- •Veno-Venous- ECMO
- •Minimum of 24h planned ECMO- therapy
排除标准
- •• 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
研究组 & 干预措施
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
干预措施: Alprostadil (Drug)
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
干预措施: 0.9% sodium chloride solution (Drug)
结局指标
主要结局
Bleeding rate (quantified by the number of packed red blood cells transfused in relation to the duration of ECMO therapy)
时间窗: 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.
次要结局
- number of bleeding incidences and severity of bleeding (bleeding grades)(up to six months)
- Number of Clotting Events(up to six months)
- Function of the membrane oxygenator(up to six 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)
- number of platelet transfusions, fresh frozen plamsa, coagulation interventions etc.(up to six months)
- Number of changes of the membrane oxygenator relative to the duration of ECMO therapy(up to six months)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- number of platelet transfusions(up to six months)
- number of coagulation interventions(up to six months)
研究者
Thomas Staudinger
Ao.Univ.Prof. Dr. med
Medical University of Vienna