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
|First Submitted Date ICMJE||September 16, 2005|
|First Posted Date ICMJE||September 22, 2005|
|Last Update Posted Date||May 6, 2008|
|Study Start Date ICMJE||July 2004|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Clinically relevant reduction of RVD [ Time Frame: 24 hours from Tenecteplase or Placebo injection ]|
|Original Primary Outcome Measures ICMJE
||• Clinically relevant reduction of RVD at 24 hours from Tenecteplase or Placebo injection|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Tenecteplase Pulmonary Embolism Italian Study|
|Official Title ICMJE||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|
|Brief Summary||To assess the efficacy and safety of Tenecteplase versus Placebo in normotensive patients with sub-massive Pulmonary Embolism and Right Ventricular Dysfunction (RVD) all receiving unfractionated heparin (UFH)|
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 ICMJE||Interventional|
|Study Phase ICMJE||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Condition ICMJE||Pulmonary Embolism|
|Intervention ICMJE||Drug: tenecteplase|
|Study Arms ICMJE||Not Provided|
|Publications *||Becattini C, Agnelli G, Salvi A, Grifoni S, Pancaldi LG, Enea I, Balsemin F, Campanini M, Ghirarduzzi A, Casazza F; TIPES Study Group. Bolus tenecteplase for right ventricle dysfunction in hemodynamically stable patients with pulmonary embolism. Thromb Res. 2010 Mar;125(3):e82-6. doi: 10.1016/j.thromres.2009.09.017. Epub 2009 Oct 14.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Terminated|
|Estimated Enrollment ICMJE
|Original Enrollment ICMJE||Same as current|
|Estimated Study Completion Date ICMJE||July 2006|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages ICMJE||18 Years to 85 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Italy|
|Removed Location Countries|
|NCT Number ICMJE||NCT00222651|
|Other Study ID Numbers ICMJE||CRU-UniPg-01-02|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Department of Internal Medicine, University of Perugia|
|Study Sponsor ICMJE||University Of Perugia|
|Collaborators ICMJE||Not Provided|
|PRS Account||University Of Perugia|
|Verification Date||April 2008|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP