Tenecteplase Pulmonary Embolism Italian Study

This study has been terminated.
(competitor study about to start)
Sponsor:
Information provided by:
University Of Perugia
ClinicalTrials.gov Identifier:
NCT00222651
First received: September 16, 2005
Last updated: April 29, 2008
Last verified: April 2008
  Purpose

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)


Condition Intervention Phase
Pulmonary Embolism
Drug: tenecteplase
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University Of Perugia:

Primary Outcome Measures:
  • Clinically relevant reduction of RVD [ Time Frame: 24 hours from Tenecteplase or Placebo injection ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinically relevant reduction of RVD; Clinical deterioration requiring escalation of treatment [ Time Frame: 7 days from Tenecteplase or Placebo ] [ Designated as safety issue: No ]
  • PE recurrence [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Death [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 180
Study Start Date: July 2004
Estimated Study Completion Date: July 2006
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.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00222651

Locations
Italy
Dipartimento di Cardiologia - Ospedale del Delta
Lagosanto, Ferrara, Italy, 44023
Unità Operativa di Cardiologia - Azienda Ospedaliera - Ospedale Civile di Vimercate
Desio, Milano, Italy, 20033
Divisione di Cardiologia - Azienda Ospedaliera - Ospedale Civile di Legnano
Legnano, Milano, Italy, 2025
Unità Operativa di Cardiologia - Ospedale di Circolo e Fondazione Macchi
Varese, Milano, Italy, 21100
Divisione Medica II - Ospedale di Vimercate
Vimercate, Milano, Italy, 22059
Medicina D'Urgenza e Pronto Soccorso - Opsedale Regionale
Ancona, Italy, 60020
Divisione di Cardiologia - Azienda Ospedaliera di Venere -Giovanni XXIII
Bari, Italy, 70012
Medicina d'Urgenza - Policlinico S. Orsola
Bologna, Italy
U.O. di Cardiologia - Ospedale di Bentivoglio
Bologna, Italy, 40010
Reparto di Cardiologia - Casa di Cura Poliambulanza - Congregazione Suore Ancelle della Carità
Brescia, Italy, 25124
UTIC - Ospedale Civile di Brescia
Brescia, Italy, 25100
Medicina D'Urgenza, Cardiologia - Ospedale Civile "San Sebastiano"
Caserta, Italy, 81100
Dipartimento di Emergenza Accettazione - Azienda Ospedaliera Universitaria Careggi
Firenze, Italy, 50100
Dipartimento di Emegernza e Accetazione (DEA) - Az. Ospedale-Università San Martino di Genova
Genova, Italy, 16132
Divisione Medica II - Ospedale Galliera
Genova, Italy, 16128
Reparto di Cardiologia - Presidio Ospedaliero Piana di Lucca
Lucca, Italy, 55100
Dipartimento Cuore Polmone - Ospedale Carlo Poma
Mantova, Italy, 46100
Reparto di Pneumologia - Ospedale San Giuseppe
Milano, Italy, 20123
Reparto di Cardiologia - Azienda Ospedaliera Fatebenfratelli Oftalmico
Milano, Italy, 20121
Unità Operativa di Cardiologia - Ospedale S Carlo Borromeo
Milano, Italy, 20153
Medicina D'Urgenza - Az. Osped. Ospedale Niguarda "Cà Granda"
Milano, Italy, 20162
Medicina D'Urgenza - Ospedale Maggiore Policlinico
Milano, Italy, 20122
Medicina Interna II - Azienda Ospedaliera "Maggiore della Carità" di Novara
Novara, Italy, 28100
Department of Internal Medicine - University of Perugia
Perugia, Italy, 06129
Malattie Apparato Respiratorio - Ospedale Cisanello
Pisa, Italy, 56124
Reparto di Angiologia - Arcispedale Santa Maria Nuova
Reggio Emilia, Italy, 42100
Divisione di Cardiologia - Ospedale Civile
Rovigo, Italy, 45100
Divisione di Pneumologia - Ospedale S Maria
Terni, Italy, 05100
Medicina D'Urgenza - Azienda Ospedaliera S. Giovanni Battista "Le Molinette"
Torino, Italy, 10100
Medicina D'Urgenza - Ospedale Cattinara
Trieste, Italy, 34100
Sponsors and Collaborators
University Of Perugia
Investigators
Study Chair: Giancarlo Agnelli, MD Department of Internal Medicine - University of Perugia
Study Director: Cecilia Becattini, MD Department of Internal Medicine - University of Perugia
  More Information

No publications provided by University Of Perugia

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Department of Internal Medicine, University of Perugia
ClinicalTrials.gov Identifier: NCT00222651     History of Changes
Other Study ID Numbers: CRU-UniPg-01-02
Study First Received: September 16, 2005
Last Updated: April 29, 2008
Health Authority: Italy: Ministry of Health
Italy: The Italian Medicines Agency

Keywords provided by University Of Perugia:
pulmonary embolism
right ventricular dysfunction
thrombolysis
echocardiography

Additional relevant MeSH terms:
Embolism
Pulmonary Embolism
Ventricular Dysfunction
Ventricular Dysfunction, Right
Cardiovascular Diseases
Embolism and Thrombosis
Heart Diseases
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Tenecteplase
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014