Clinical Trial: IMPI 2 - A Trial of Intrapericardial Alteplase in Large Pericardial Effusion

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Trial of Complete Percutaneous Pericardial Drainage Facilitated by Intrapericardial Alteplase Compared to Conventional Pericardiocentesis When Indicated in Adults With Large Pe

Brief Summary: 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.

Detailed Summary:

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:

  1. To demonstrate the feasibility of conducting a multicentre clinical trial of intrapericardial fibrinolysis in patients with large pericardial effusion,
    Sponsor: University of Cape Town

    Current Primary Outcome: Composite outcome of cardiac tamponade requiring pericardiocentesis or constrictive pericarditis. [ Time Frame: 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.



    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Major bleeding [ Time Frame: 12 months ]
      Defined as clinically overt bleeding accompanied by one or more of the following: a decrease in the haemoglobin level of 2 g per decilitre or more over a 24-hour period, transfusion of 2 or more units of packed red cells, bleeding at a critical site (intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, or retroperitoneal), or fatal bleeding
    • Clinically relevant non-major bleeding [ Time Frame: 12 months ]
      Defined as clinically overt bleeding that does not satisfy the criteria for major bleeding and that leads to hospital admission, physician-guided medical or surgical treatment.
    • Any bleeding [ Time Frame: 12 months ]
      Any other form of bleeding that is not covered by safety outcomes 1-3
    • Other adverse events [ Time Frame: 12 months ]
      Any other adverse events
    • Persistent pericardial effusion without cardiac tamponade [ Time Frame: 12 months ]
      Refers to the echocardiographic presence of a pericardial effusion without criteria for cardiac tamponade requiring pericarditis during follow-up visits. The pericardial effusion is the same size or larger than that measured at the time of enrollment (where no pericardiocentesis was done) or post-pericardiocentesis.
    • Recurrent pericardial effusion without cardiac tamponade [ Time Frame: 12 months ]
      Refers to the echocardiographic presence of a pericardial effusion without criteria for cardiac tamponade requiring pericarditis during follow-up visits. Recurrence is present in the context of re-appearance of a pericardial effusion in the context where complete drainage was performed.
    • Hospitalisation for any cause; and death from any cause [ Time Frame: 12 months ]
      Refers to admission to hospital for at least 24 hours for any reason.
    • Cardiac tamponade requiring pericardiocentesis [ Time Frame: 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 [ Time Frame: 12 months ]
      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.
    • Death [ Time Frame: 12 months ]
      Death from any cause


    Original Secondary Outcome: Same as current

    Information By: University of Cape Town

    Dates:
    Date Received: February 1, 2016
    Date Started: February 2016
    Date Completion: January 2020
    Last Updated: February 1, 2016
    Last Verified: February 2016