Tenecteplase Pulmonary Embolism Italian Study
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|ClinicalTrials.gov Identifier: NCT00222651|
Recruitment Status : Terminated (competitor study about to start)
First Posted : September 22, 2005
Last Update Posted : May 6, 2008
|Condition or disease||Intervention/treatment||Phase|
|Pulmonary Embolism||Drug: tenecteplase||Phase 2|
In patients with major acute PE thrombolysis has been shown to be life saving (22). Recent registries showed the beneficial effect of thrombolysis also in patients with PE not associated with shock or hypotension (4-23). In these patients thrombolytic treatment has been shown to obtain an improvement of 37% in lung perfusion, detected by lung scan, with respect to an improvement of 18.8% obtained by heparin treatment (24). In a different trial, rt-PA resulted in a faster and greater improvement of pulmonary artery hypertension than heparin treatment (25). Indeed, PE has a wide spectrum of severity at presentation and it is conceivable that the use of more aggressive treatments should be reserved to patients at high risk for adverse outcome. Hence, the search started of prognostic factors of adverse outcome in patients with pulmonary embolism.
RVD has been associated with early adverse outcome (PE recurrence and mortality) in patients with acute PE (26-28; 3). In-hospital mortality in PE patients with and without echocardiographic RVD has been found to be 18.4% and 5.7%, respectively (3). Ribeiro et al. found a higher mortality in patients with PE and severe RVD: in-hospital mortality was 7.9% in the overall population with respect to 14.3% in patients with severe RVD (5). The ICOPER registry reported a 2-week mortality of 15.9% in patients presenting with RVD in comparison with 8% in patients without RVD (23). In MAPPET 10% of patients with RVD died within 30 days as compared to 4.1% of patients without (4).
RVD is a common finding in patients with acute PE and normal blood pressure (BP) (29-33). Recent data suggest that patients with objectively confirmed PE, normal BP and echocardiographic evidence of RVD have a high incidence of adverse outcome (7) and may potentially benefit from more aggressive treatment (34-35). In a recent study patients with acute PE were classified according to the presence of RVD and hypotension; the short-term mortality and the incidence of PE-related shock in patients with normal BP and echo RVD was respectively 5% and 10%. None of the patients with normal BP and no RVD died or experienced PE-related shock (6).
It has been recently demonstrated in patients with PE and pulmonary hypertension or RVD but without arterial hypotension or shock, that rt-PA significantly reduces the incidence of adverse in-hospital outcome events (death and clinical deterioration) with respect to heparin (8).
Consecutive patients with symptomatic PE, since no more than four days, confirmed by objective testing (high probability lung scan or intermediate probability lung scan and objectively confirmed deep vein thrombosis or spiral CT or pulmonary angiography or TE echocardiography) will undergo echocardiographic examination within 24 hour from diagnosis. Patients with RVD and normal BP (Systolic BP> 100 mmHg) will be included in the study.
180 patients will be randomized in the study. The patients included in the study will be randomized, in a double blind fashion, to receive Tenecteplase + UFH (90 patients) or Placebo + UFH (90 patients).
Study treatment should be administered within 6 hours from echocardiography. Echocardiography will be repeated at 24 hours and 7 days or discharge (whichever comes first) from Tenecteplase or Placebo injection. A Follow-up visit at 30 days from randomization will include: clinical history, physical examination and ECG and an echocardiographic examination.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||180 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Phase II Multicenter, Randomized, Double Blind Study Comparing the Efficacy and Safety of Single Bolus i.v. Tenecteplase Versus Placebo in Normotensive Patients With Pulmonary Embolism and Right Ventricular Dysfunction|
|Study Start Date :||July 2004|
|Estimated Study Completion Date :||July 2006|
- Clinically relevant reduction of RVD [ Time Frame: 24 hours from Tenecteplase or Placebo injection ]
- Clinically relevant reduction of RVD; Clinical deterioration requiring escalation of treatment [ Time Frame: 7 days from Tenecteplase or Placebo ]
- PE recurrence [ Time Frame: 30 days ]
- Death [ Time Frame: 30 days ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00222651
|Study Chair:||Giancarlo Agnelli, MD||Department of Internal Medicine - University of Perugia|
|Study Director:||Cecilia Becattini, MD||Department of Internal Medicine - University of Perugia|