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Tenecteplase Pulmonary Embolism Italian Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00222651
Recruitment Status : Terminated (competitor study about to start)
First Posted : September 22, 2005
Last Update Posted : May 6, 2008
Sponsor:
Information provided by:
University Of Perugia

Tracking Information
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
 (submitted: April 29, 2008)
Clinically relevant reduction of RVD [ Time Frame: 24 hours from Tenecteplase or Placebo injection ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 19, 2005)
• Clinically relevant reduction of RVD at 24 hours from Tenecteplase or Placebo injection
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2008)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2005)
  • • Clinically relevant reduction of RVD at 7 days from Tenecteplase or Placebo injection,
  • • Clinical deterioration within 7 days from Tenecteplase or Placebo injection requiring escalation of treatment, defined as:
  • o Secondary thrombolysis for one of the following indications:
  • a) deteriorating clinical symptoms, particularly dyspnea, or worsening respiratory failure due to pulmonary embolism;
  • b) persistent or worsening pulmonary hypertension or right ventricular dysfunction on echocardiography or right heart catheterization;
  • o Endotracheal intubation,
  • o Cardiopulmonary resuscitation,
  • o Emergency surgical embolectomy or catheter thrombus fragmentation.
  • • Haemodynamic collapse within 7 days from Tenecteplase or Placebo injection defined as systolic blood pressure <90mmHg or a drop >40mmHg for at least 30 minutes (or the need for supportive measures to maintain systolic blood pressure >90mmHg) with sign
  • • PE recurrence at 30 days
  • • Death at 30 days
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
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)
Detailed Description

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 Information
Recruitment Status  ICMJE Terminated
Estimated Enrollment  ICMJE
 (submitted: September 19, 2005)
180
Original Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2006
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • age between 18 and 85;
  • symptomatic PE confirmed by: high probability lung scan, or intermediate probability lung scan and objectively confirmed deep vein thrombosis, or spiral CT-scan or pulmonary angiography or TE echocardiography;
  • normal blood pressure (SBP >100mmHg);
  • RVD at echocardiography (see criteria);
  • written informed consent.

Exclusion Criteria:

  • absence of RVD at echocardiography;
  • shock or hypotension (SBP < 100 mmHg);
  • therapeutic heparin (UFH or LMWH) treatment for more than 48 hours prior to randomization;
  • administration of thrombolytic agents within the previous 4 days;
  • vena cava filter insertion or pulmonary thrombectomy within the previous 4 days
  • chronic pulmonary hypertension or severe COPD;
  • hypertension defined as blood pressure >180/110 mm Hg (systolic BP >180 mm Hg and/or diastolic BP >110 mm Hg) on a single, reliable measurement during current admission at enrolling site prior to randomisation;
  • use of GP IIb/IIIa antagonists within the preceding 7 days;
  • significant bleeding disorders either at present or within the past 6 months;
  • active peptic ulceration;
  • known diabetic haemorrhagic retinopathy or other haemorrhagic ophthalmic conditions;
  • known haemorrhagic diathesis;
  • known arterial aneurysm and known arterial/venous malformation;
  • known neoplasm with increased bleeding risk;
  • prolonged cardiopulmonary resuscitation (>10 minutes) in the previous two weeks;
  • current oral anticoagulation;
  • major surgery, biopsy of a parenchymal organ, or significant trauma within the past 2 months;
  • any known history of stroke or transient ischaemic attack (TIA) or dementia;
  • any recent head trauma and any other trauma occurring after onset of the current pulmonary embolism;
  • any known history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery);
  • known subacute bacterial endocarditis;
  • known acute pancreatitis;
  • known severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension
  • (oesophageal varices) and active hepatitis;
  • pregnancy or lactation or parturition within the previous 30 days;
  • women of childbearing potential must have a negative pregnancy test, or use a medically accepted method of birth control;
  • treatment with an investigational drug under another study protocol in the past 7 days;
  • previous enrolment in this study;
  • known hypersensitivity to Tenecteplase, Alteplase, unfractionated heparin, or to any of the excipients;
  • anticipated or obvious problem with vascular access;
  • any other condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated;
  • inability to follow protocol requirements
Sex/Gender  ICMJE
Sexes Eligible for Study: All
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  
 
Administrative Information
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
Investigators  ICMJE
Study Chair: Giancarlo Agnelli, MD Department of Internal Medicine - University of Perugia
Study Director: Cecilia Becattini, MD Department of Internal Medicine - University of Perugia
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