A Trial of Complete Percutaneous Pericardial Drainage Facilitated by Intrapericardial Alteplase Compared to Conventional Pericardiocentesis When Indicated in Adults With Large Pericardial Effusion Due to Tuberculous and Non-tuberculous Pericarditis
试验速览
- 阶段
- 3 期
- 入组人数
- 2,176
- 试验地点
- 2
- 主要终点
- Composite outcome of cardiac tamponade requiring pericardiocentesis or constrictive pericarditis.
研究概览
简要总结
The Second Investigation of the Management of Pericarditis (IMPI-2) Trial will compare the effectiveness and safety of complete percutaneous pericardial drainage facilitated by intrapericardial alteplase (recombinant human tissue-type plasminogen activator) to conventional pericardiocentesis when indicated in 2176 patients with large pericardial effusion due to tuberculous and non-tuberculous pericarditis. An internal pilot study of 218 patients will initially confirm the feasibility of conducting a large-scale multi-centre clinical trial of intrapericardial fibrinolysis in patients with large pericardial effusion, and also provide preliminary safety data, following a dose finding study of intrapericardial alteplase.
详细描述
Intrapericardial fibrinolytic agents are used in the drainage of tuberculous, purulent, neoplastic and other inflammatory pericardial effusions to prevent recurrent effusions and constrictive pericarditis. This use is based on evidence from case reports and a small trial that did not have the statistical power to reliably evaluate the effect of pericardial drainage facilitated by intrapericardial fibrinolysis on safety and important clinical outcomes.
The Second Investigation of the Management of Pericarditis (IMPI-2) Trial will compare the effectiveness and safety of complete percutaneous pericardial drainage facilitated by intrapericardial alteplase (recombinant human tissue-type plasminogen activator) to conventional pericardiocentesis when indicated in 2176 patients with large pericardial effusion due to tuberculous and non-tuberculous pericarditis. An internal pilot study of 218 patients will initially confirm the feasibility of conducting a large-scale multi-centre clinical trial of intrapericardial fibrinolysis in patients with large pericardial effusion, and also provide preliminary safety data, following a dose finding study of intrapericardial alteplase.
Hypothesis: We hypothesise that patients with large pericardial effusion randomized to intrapericardial alteplase to ensure complete pericardial drainage will have at least a 35% reduction in cardiac tamponade requiring pericardiocentesis or constrictive pericarditis compared to conventional pericardiocentesis when indicated.
Objectives: The primary objectives of the IMPI-2 Trial are:
- To demonstrate the feasibility of conducting a multicentre clinical trial of intrapericardial fibrinolysis in patients with large pericardial effusion, and to assess the safety of intrapericardial alteplase in an internal pilot study, and
- To determine the effectiveness of intrapericardial alteplase in reducing the composite outcome of cardiac tamponade requiring pericardiocentesis or constrictive pericarditis in patients with large pericardial effusion in the full trial.
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
- Single (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
- •Age ≥ 18 years of age;
- •Confirmed large pericardial effusion on echocardiography (i.e., echo free space ≥1 cm anterior to the right ventricle of the heart in diastole);
- •Willingness to participate for the full duration of the trial (i.e., 12 months); and
- •Provision of written informed consent.
排除标准
- •Age < 18 years;
- •Uraemic pericarditis (i.e., urea > 21.4 mmol/l);
- •Thrombocytopenia (i.e., < 100,000 platelets per µl);
- •Presence of a contra-indication to the administration of a fibrinolytic agent (i.e., major haemorrhage or major trauma; coincidental stroke; major surgery in the previous 5 days; blood pressure >200/100 mmHg).
研究组 & 干预措施
Pericardiocentesis with Alteplase
Complete percutaneous pericardial drainage facilitated by intrapericardial alteplase.
干预措施: Pericardiocentesis with Alteplase (Other)
Conventional Pericardiocentesis
Conventional pericardiocentesis when indicated.
干预措施: Conventional Pericardiocentesis (Other)
结局指标
主要结局
Composite outcome of cardiac tamponade requiring pericardiocentesis or constrictive pericarditis.
时间窗: 12 months
Cardiac tamponade requiring pericardiocentesis shall refer to a combination of physical and echocardiographic findings, i.e., patients with clinical signs of tachycardia (\> 90 bpm), hypotension (systolic blood pressure \< 100 mmHg), elevated jugular venous pressure and/or pulsus paradoxus \> 10 mmHg plus evidence of a large pericardial effusion with echocardiographic signs of tamponade in the absence of other cardiac disease, as defined in the IMPI trial. Constrictive pericarditis shall refer to a combination of physical and echocardiographic findings (i.e., patients with a prior history of pericardial effusion who have pulsus paradoxus, a raised jugular venous pressure with or without evidence of pericardial thickening on imaging) in the absence of either large pericardial effusion or other cardiac disease, as described in the IMPI trial.
次要结局
- Major bleeding(12 months)
- Clinically relevant non-major bleeding(12 months)
- Any bleeding(12 months)
- Other adverse events(12 months)
- Persistent pericardial effusion without cardiac tamponade(12 months)
- Recurrent pericardial effusion without cardiac tamponade(12 months)
- Hospitalisation for any cause; and death from any cause(12 months)
- Cardiac tamponade requiring pericardiocentesis(12 months)
- Constrictive pericarditis(12 months)
- Death(12 months)
研究者
Bongani M Mayosi
Professor of Medicine
University of Cape Town