Strategies for Anticoagulation During Venovenous ECMO: The SAFE-ECMO Pilot Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 2
- 主要终点
- Number of Participants With Major Bleeding Events
研究概览
简要总结
Moderate intensity titrated dose anticoagulation has been used in patients receiving extracorporeal membrane oxygenation (ECMO) to prevent thromboembolism and thrombotic mechanical complications. As technology has improved, however, the incidence of thromboembolic events has decreased, leading to re-evaluation of the risks of anticoagulation, particularly during venovenous (V-V) ECMO. Recent data suggest that bleeding complications during V-V ECMO may be more strongly associated with mortality than thromboembolic complications, and case series have suggested that V-V ECMO can be safely performed without moderate or high intensity anticoagulation. At present, there is significant variability between institutions in the approach to anticoagulation during V-V ECMO. A definitive randomized controlled trial is needed to compare the effects of a low intensity fixed dose anticoagulation (low intensity) versus moderate intensity titrated dose anticoagulation (moderate intensity) on clinical outcomes during V-V ECMO. Before such a trial can be conducted, however, additional data are needed to inform the feasibility of the future trial.
详细描述
Since the inception of Extracorporeal Membrane Oxygenation (ECMO), moderate intensity titrated dose anticoagulation has been used to prevent clinically harmful thromboembolism and thrombotic mechanical complications. The impact of thromboembolic events on clinical outcomes during venovenous (V-V) extracorporeal membrane oxygenation (ECMO), however, is unclear, and complications related to bleeding are common and associated with increased morbidity and mortality. These findings have led many experts to suggest that anticoagulation strategies during V-V ECMO should be re-evaluated.
Critical illness, in general, is associated with both coagulopathy and impaired hemostasis. These problems are compounded during ECMO by the artificial interface between blood and the non-biologic surface of the circuit components, which leads to activation of the coagulation system, consumptive thrombocytopenia, fibrinolysis, and thrombin generation. The sheer stress on blood components during ECMO also lead to destruction of high-molecular-weight von Willebrand multimers, interrupting primary hemostasis.
Both bleeding and thromboembolism are common complications during ECMO. Bleeding events have been associated with poor clinical outcomes, likely mediated by an increased incidence of intracranial hemorrhage during ECMO. During intra-operative cardiopulmonary bypass and venoarterial (V-A) ECMO, ischemic strokes are a common and potentially deadly complication. During V-V ECMO, however, the majority of thromboembolic events are cannula-associated DVT and circuit thromboses requiring exchange, which are of unclear clinical significance.
Various anticoagulation strategies have been proposed to balance the risks of bleeding and thromboembolism during V-V ECMO, including high intensity anticoagulation, moderate intensity anticoagulation, and low intensity anticoagulation (the equivalent of DVT prophylaxis). Observational studies have suggested that, compared to moderate intensity anticoagulation, low intensity anticoagulation reduces transfusion requirements without affecting the incidence of thrombosis, hemorrhage, or death. In one case series of 60 patients who were treated with only low-intensity subcutaneous heparin during V-V ECMO, rates of transfusions were lower than historical controls without any effect on the rate of thrombotic events. Similarly, a recent systematic review suggested that the rates of thromboembolism and circuit thrombosis among patients managed with a moderate intensity anticoagulation strategy during V-V ECMO were comparable to the rates reported among patients managed with a less intense anticoagulation strategy.
To date, there are no randomized controlled trials comparing low intensity to moderate intensity anticoagulation during V-V ECMO. Guidelines from the Extracorporeal Life Support Organization (ELSO), the pre-eminent group for ECMO education and research, provide little guidance for the selection of anticoagulation strategy, and anticoagulation practices are highly variable across institutions. A large, multicenter, randomized trial is needed to determine the ideal strategy to anticoagulation during V-V ECMO. Before such a trial can be conducted, however, additional data are needed on the feasibility of randomizing patients to a specific anticoagulation strategy and study measurements.
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
- None
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
- •Patient receiving V-V ECMO
- •Patient is located in a participating unit of the Vanderbilt University Medical Center (VUMC) adult hospital.
排除标准
- •Patient is pregnant
- •Patient is a prisoner
- •Patient is < 18 years old
- •Patient underwent ECMO cannulation greater than 24 hours prior to screening
- •Presence of an indication for systemic anticoagulation:
- •Ongoing receipt of systemic anticoagulation
- •Planned administration of anticoagulation for an indication other than ECMO
- •Presence of or plan to insert an arterial ECMO cannula
- •Presence of a contraindication to anticoagulation:
- •Active bleeding determined by treating clinicians to make anticoagulation unsafe
- •Major surgery or trauma less than 72 hours prior to randomization
- •Known history of a bleeding diathesis
- •Ongoing severe thrombocytopenia (platelet count < 30,000)
- •History of heparin-induced thrombocytopenia (HIT)
- •Heparin allergy
- •Positive SARS-CoV-2 test within prior 21 days or high clinical suspicion for COVID-19
- •The treating clinician determines that the patient's risks of thromboembolism or bleeding necessitate a specific approach to anticoagulation management during V-V ECMO
结局指标
主要结局
Number of Participants With Major Bleeding Events
时间窗: From randomization to the date of death or the date 24 hours after decannulation, whichever came first, through study completion, up to 134 days.
Major bleeding event, according to the International Society on Thrombosis and Hemostasis, defined as: 1. Fatal bleeding 2. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome 3. Clinically overt bleeding associated with either a drop in hemoglobin level by at least 2.0 grams/dL or leading to transfusion of two or more units of packed red blood cells
Number of Participants With Thromboembolic Events
时间窗: From randomization to the date of death or the date 24 hours after decannulation, whichever came first, through study completion, up to 134 days.
Thromboembolic event defined as: 1. Deep venous thrombosis (DVT) 2. Acute pulmonary embolism (PE) 3. Intra-cardiac thrombosis 4. Ischemic stroke 5. Acute circuit thrombosis requiring urgent circuit exchange 6. Acute arterial thromboembolism
次要结局
- Number of Participants With Cannula-associated Deep Vein Thrombosis(24-72 hours after decannulation)
- Number of Circuit or Circuit Component Exchanges(From randomization to the date of death or decannulation, whichever came first, through study completion, up to 134 days)
- New Heparin Induced Thrombocytopenia Diagnosis(From randomization to the date of death or decannulation, whichever came first, through study completion, up to 134 days)
- Lowest Platelet Count(From randomization to the the date of death or the date 24 hours after decannulation, whichever came first, through study completion, up to 134 days)
- Highest Total Bilirubin Values(From randomization to the the date of death or the date 24 hours after decannulation, whichever came first, through study completion, up to 134 days)
- Highest Lactate Dehydrogenase Value(From randomization to the the date of death or the date 24 hours after decannulation, whichever came first, through study completion, up to 134 days)
- Death Attributable to a Major Bleeding Event(From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days)
- Death Attributable to a Thromboembolic Event(From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days)
- Ventilator-free Days(From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days)
- ICU Length of Stay(From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days)
- Hospital Length of Stay(From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days)
- In-hospital Mortality(From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days)
研究者
Whitney Gannon
Acute Care Nurse Practitioner
Vanderbilt University Medical Center