A Pragmatic Pilot Randomised Phase II Controlled Trial of Prothrombin Complex Concentrates (PCC) Versus Fresh Frozen Plasma (FFP) in Adult Patients Who Are Undergoing Heart Surgery
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Recruitment rate
研究概览
简要总结
The PROPHESY trial is a single centre pilot trial investigating Fresh Frozen Plasma (FFP) or Prothrombin Complex Concentrate (PCC) treatment for patients who are bleeding during cardiac surgery, and who are NOT receiving a vitamin K antagonist agent (e.g. warfarin).
This pilot study will investigate the feasibility of delivering the different components of the trial, so that investigators can determine if it's feasible to move to a future large trial that will aim to compare the efficacy and safety of FFP versus PCC in adult patients who are actively bleeding during cardiac surgery.
详细描述
There are ~ 30,000 cardiac procedures performed each year in the United Kingdom (UK), and it is estimated that ~30% of these cases require plasma transfusion for management of bleeding during cardiovascular surgery. Bleeding after cardiac surgery that requires blood transfusion is associated with significant morbidity and mortality, resulting in substantial costs to the health service.
There have been no clinical trials that have compared the safety and efficacy of FFP versus PCC in cardiac surgery in patients who are bleeding, and who are not on vitamin K antagonists. In the UK, FFP transfusion is the standard treatment for management of bleeding: however, the use of PCC in this setting is rising, with several observational studies now demonstrating that it is safe, and that its administration is associated with reduced blood transfusion requirements, albeit no difference in other outcomes. Potential advantages of PCC over FFP are: increased concentration of clotting factors leading to faster improvement of reversing coagulopathy; improved ease and speed of administration; reduced fluid volume; and reduced incidence of immune modulatory side effects.
While observational studies have suggested that PCC can be safely administered in bleeding patients undergoing cardiac surgery, the clinical equipoise and, the lack of high quality evidence means that a randomised control trial is required to compare the clinical efficacy and safety of both in bleeding patients undergoing cardiac surgery not relating to warfarin. Prior to such a trial, the investigators will perform a single-centre pilot study to assess if individual components of a large trial are deliverable.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 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
- •Age ≥18 years
- •Able to give consent
- •Any cardiovascular surgeries excluding procedures under exclusion criteria
排除标准
- •Unable to consent
- •Patients refusing blood transfusion for any reason
- •First time isolated coronary artery bypass grafts (CABG)
- •First time isolated aortic valve replacement (excluding active endocarditis)
- •Thoraco-abdominal surgeries
- •Minor surgeries that do not involve cardiopulmonary bypass
- •Use of warfarin within four days
- •Use of direct oral anticoagulants (i.e. dabigatran, rivaroxaban, apixaban or edoxaban) within 48 hrs (or 72 hours if patient has renal impairment - i.e. estimated glomerular filtration rate of <30ml/min)
- •Inherited bleeding disorder (i.e. any inherited clotting factor deficiencies, or platelet disorders)
- •Pregnancy
- •Known or suspected allergy to FFP or PCC
- •Known or suspected allergy to heparin, Sodium citrate dihydrate, sodium dihydrogenphosphate dihydrate and Glycine
- •History of Heparin-induced thrombocytopenia
- •Individuals who have Immunoglobulin A (IgA) deficiency with known antibodies against IgA
- •Documented venous thromboembolism in the last three months
- •Documented antiphospholipid syndrome
- •Severe protein S deficiency
- •Participation in another clinical trial, where the patient has received Investigational Medicinal Product in the last 3 months
研究组 & 干预措施
Fresh Frozen Plasma (FFP)
Patients randomised to the comparator arm will receive Fresh Frozen Plasma (FFP)
FFP will be provide as a solution for intravenous administration, once thawed.
The dose of the FFP will be ~ 15 mL/kg.
Subjects may receive multiple doses of FFP as required if bleeding continues, as per usual care
干预措施: Fresh Frozen Plasma (Biological)
Prothrombin Complex Concentrate (PCC)
Patients randomised to the experimental arm will receive PCC at ~15 IU/kg. PCC will be reconstituted into a solution for intravenous administration.
Subjects will receive a single dose of PCC, and if bleeding continues, standard treatment will be administered
干预措施: Prothrombin Complex Concentrate (PCC) (Drug)
结局指标
主要结局
Recruitment rate
时间窗: Within 24 hours of surgery
Proportion of eligible patients who consent to the study Proportion of patients who have consented and who bleed within 24 hours and who require FFP transfusion.
次要结局
- Delivery of different components of the trial to see if a larger trial is feasible(Collected at 90 days or death, whichever occurs first)
- To compare the impact of FFP and PCC on the haemostatic capacity of bleeding patients after cardiac surgery(Within 24 hours of surgery)
- Qualitative research involving completion of a Delphi survey to apprise the management and conduct of a larger trial(Completed over a 4 month period during the study follow-up stage)
- Qualitative research involving interviews of patients and healthcare professionals involved in PROPHESY to apprise the management and conduct of a larger trial(By the 90 days end of study visit)