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Tenecteplase Pulmonary Embolism Italian Study

Primary Purpose

Pulmonary Embolism

Status
Terminated
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
tenecteplase
Sponsored by
University Of Perugia
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Embolism focused on measuring pulmonary embolism, right ventricular dysfunction, thrombolysis, echocardiography

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Dipartimento di Cardiologia - Ospedale del Delta
  • Unità Operativa di Cardiologia - Azienda Ospedaliera - Ospedale Civile di Vimercate
  • Divisione di Cardiologia - Azienda Ospedaliera - Ospedale Civile di Legnano
  • Unità Operativa di Cardiologia - Ospedale di Circolo e Fondazione Macchi
  • Divisione Medica II - Ospedale di Vimercate
  • Medicina D'Urgenza e Pronto Soccorso - Opsedale Regionale
  • Divisione di Cardiologia - Azienda Ospedaliera di Venere -Giovanni XXIII
  • U.O. di Cardiologia - Ospedale di Bentivoglio
  • Medicina d'Urgenza - Policlinico S. Orsola
  • UTIC - Ospedale Civile di Brescia
  • Reparto di Cardiologia - Casa di Cura Poliambulanza - Congregazione Suore Ancelle della Carità
  • Medicina D'Urgenza, Cardiologia - Ospedale Civile "San Sebastiano"
  • Dipartimento di Emergenza Accettazione - Azienda Ospedaliera Universitaria Careggi
  • Divisione Medica II - Ospedale Galliera
  • Dipartimento di Emegernza e Accetazione (DEA) - Az. Ospedale-Università San Martino di Genova
  • Reparto di Cardiologia - Presidio Ospedaliero Piana di Lucca
  • Dipartimento Cuore Polmone - Ospedale Carlo Poma
  • Reparto di Cardiologia - Azienda Ospedaliera Fatebenfratelli Oftalmico
  • Medicina D'Urgenza - Ospedale Maggiore Policlinico
  • Reparto di Pneumologia - Ospedale San Giuseppe
  • Unità Operativa di Cardiologia - Ospedale S Carlo Borromeo
  • Medicina D'Urgenza - Az. Osped. Ospedale Niguarda "Cà Granda"
  • Medicina Interna II - Azienda Ospedaliera "Maggiore della Carità" di Novara
  • Department of Internal Medicine - University of Perugia
  • Malattie Apparato Respiratorio - Ospedale Cisanello
  • Reparto di Angiologia - Arcispedale Santa Maria Nuova
  • Divisione di Cardiologia - Ospedale Civile
  • Divisione di Pneumologia - Ospedale S Maria
  • Medicina D'Urgenza - Azienda Ospedaliera S. Giovanni Battista "Le Molinette"
  • Medicina D'Urgenza - Ospedale Cattinara

Outcomes

Primary Outcome Measures

Clinically relevant reduction of RVD

Secondary Outcome Measures

Clinically relevant reduction of RVD; Clinical deterioration requiring escalation of treatment
PE recurrence
Death

Full Information

First Posted
September 16, 2005
Last Updated
April 29, 2008
Sponsor
University Of Perugia
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1. Study Identification

Unique Protocol Identification Number
NCT00222651
Brief Title
Tenecteplase Pulmonary Embolism Italian Study
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 Type
Interventional

2. Study Status

Record Verification Date
April 2008
Overall Recruitment Status
Terminated
Why Stopped
competitor study about to start
Study Start Date
July 2004 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
July 2006 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
University Of Perugia

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Embolism
Keywords
pulmonary embolism, right ventricular dysfunction, thrombolysis, echocardiography

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
180 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
tenecteplase
Primary Outcome Measure Information:
Title
Clinically relevant reduction of RVD
Time Frame
24 hours from Tenecteplase or Placebo injection
Secondary Outcome Measure Information:
Title
Clinically relevant reduction of RVD; Clinical deterioration requiring escalation of treatment
Time Frame
7 days from Tenecteplase or Placebo
Title
PE recurrence
Time Frame
30 days
Title
Death
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Giancarlo Agnelli, MD
Organizational Affiliation
Department of Internal Medicine - University of Perugia
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Cecilia Becattini, MD
Organizational Affiliation
Department of Internal Medicine - University of Perugia
Official's Role
Study Director
Facility Information:
Facility Name
Dipartimento di Cardiologia - Ospedale del Delta
City
Lagosanto
State/Province
Ferrara
ZIP/Postal Code
44023
Country
Italy
Facility Name
Unità Operativa di Cardiologia - Azienda Ospedaliera - Ospedale Civile di Vimercate
City
Desio
State/Province
Milano
ZIP/Postal Code
20033
Country
Italy
Facility Name
Divisione di Cardiologia - Azienda Ospedaliera - Ospedale Civile di Legnano
City
Legnano
State/Province
Milano
ZIP/Postal Code
2025
Country
Italy
Facility Name
Unità Operativa di Cardiologia - Ospedale di Circolo e Fondazione Macchi
City
Varese
State/Province
Milano
ZIP/Postal Code
21100
Country
Italy
Facility Name
Divisione Medica II - Ospedale di Vimercate
City
Vimercate
State/Province
Milano
ZIP/Postal Code
22059
Country
Italy
Facility Name
Medicina D'Urgenza e Pronto Soccorso - Opsedale Regionale
City
Ancona
ZIP/Postal Code
60020
Country
Italy
Facility Name
Divisione di Cardiologia - Azienda Ospedaliera di Venere -Giovanni XXIII
City
Bari
ZIP/Postal Code
70012
Country
Italy
Facility Name
U.O. di Cardiologia - Ospedale di Bentivoglio
City
Bologna
ZIP/Postal Code
40010
Country
Italy
Facility Name
Medicina d'Urgenza - Policlinico S. Orsola
City
Bologna
Country
Italy
Facility Name
UTIC - Ospedale Civile di Brescia
City
Brescia
ZIP/Postal Code
25100
Country
Italy
Facility Name
Reparto di Cardiologia - Casa di Cura Poliambulanza - Congregazione Suore Ancelle della Carità
City
Brescia
ZIP/Postal Code
25124
Country
Italy
Facility Name
Medicina D'Urgenza, Cardiologia - Ospedale Civile "San Sebastiano"
City
Caserta
ZIP/Postal Code
81100
Country
Italy
Facility Name
Dipartimento di Emergenza Accettazione - Azienda Ospedaliera Universitaria Careggi
City
Firenze
ZIP/Postal Code
50100
Country
Italy
Facility Name
Divisione Medica II - Ospedale Galliera
City
Genova
ZIP/Postal Code
16128
Country
Italy
Facility Name
Dipartimento di Emegernza e Accetazione (DEA) - Az. Ospedale-Università San Martino di Genova
City
Genova
ZIP/Postal Code
16132
Country
Italy
Facility Name
Reparto di Cardiologia - Presidio Ospedaliero Piana di Lucca
City
Lucca
ZIP/Postal Code
55100
Country
Italy
Facility Name
Dipartimento Cuore Polmone - Ospedale Carlo Poma
City
Mantova
ZIP/Postal Code
46100
Country
Italy
Facility Name
Reparto di Cardiologia - Azienda Ospedaliera Fatebenfratelli Oftalmico
City
Milano
ZIP/Postal Code
20121
Country
Italy
Facility Name
Medicina D'Urgenza - Ospedale Maggiore Policlinico
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Reparto di Pneumologia - Ospedale San Giuseppe
City
Milano
ZIP/Postal Code
20123
Country
Italy
Facility Name
Unità Operativa di Cardiologia - Ospedale S Carlo Borromeo
City
Milano
ZIP/Postal Code
20153
Country
Italy
Facility Name
Medicina D'Urgenza - Az. Osped. Ospedale Niguarda "Cà Granda"
City
Milano
ZIP/Postal Code
20162
Country
Italy
Facility Name
Medicina Interna II - Azienda Ospedaliera "Maggiore della Carità" di Novara
City
Novara
ZIP/Postal Code
28100
Country
Italy
Facility Name
Department of Internal Medicine - University of Perugia
City
Perugia
ZIP/Postal Code
06129
Country
Italy
Facility Name
Malattie Apparato Respiratorio - Ospedale Cisanello
City
Pisa
ZIP/Postal Code
56124
Country
Italy
Facility Name
Reparto di Angiologia - Arcispedale Santa Maria Nuova
City
Reggio Emilia
ZIP/Postal Code
42100
Country
Italy
Facility Name
Divisione di Cardiologia - Ospedale Civile
City
Rovigo
ZIP/Postal Code
45100
Country
Italy
Facility Name
Divisione di Pneumologia - Ospedale S Maria
City
Terni
ZIP/Postal Code
05100
Country
Italy
Facility Name
Medicina D'Urgenza - Azienda Ospedaliera S. Giovanni Battista "Le Molinette"
City
Torino
ZIP/Postal Code
10100
Country
Italy
Facility Name
Medicina D'Urgenza - Ospedale Cattinara
City
Trieste
ZIP/Postal Code
34100
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
19833379
Citation
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.
Results Reference
derived

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Tenecteplase Pulmonary Embolism Italian Study

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