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PEITHO Pulmonary Embolism Thrombolysis Study

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
German Federal Ministry of Education and Research
Boehringer Ingelheim
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00639743
First received: March 13, 2008
Last updated: June 13, 2014
Last verified: June 2014
  Purpose

Heparin is the reference therapy for most patients with pulmonary embolism. Some patients with sub-massive pulmonary embolism defined by normal blood pressure and dysfunction of the right ventricle have a higher mortality risk. It has been suggested that thrombolytic treatment, a drug that dissolves blood clots more rapidly, may reduce the mortality in those patients. The studies reported to date were unable to confirm or refute this hypothesis because the number of patients included in those studies is too low. The aim of the study is to compare thrombolytic treatment with heparin (which is the reference therapy for pulmonary embolism) in a large group of patients with sub-massive pulmonary embolism.


Condition Intervention Phase
Pulmonary Embolism
Drug: placebo ( group B)
Drug: tenecteplase (group A)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Comparison Trial Evaluating Efficacy and Safety of Single i.v. Bolus Tenecteplase Plus Standard Anticoagulation as Compared With Standard Anticoagulation in Normotensive Patients

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Clinical composite endpoint of all-cause mortality or haemodynamic collapse within 7 days [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]
  • Haemodynamic collapse is defined as: need for cardiopulmonary resuscitation; or systolic blood pressure < 90 mm Hg for at least 15 min or drop of syst [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Death within 7 days [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]
  • Haemodynamic collapse within 7 days [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]
  • Confirmed symptomatic pulmonary embolism recurrence within 7 days [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]
  • Death within 30 days [ Time Frame: Day 30 ] [ Designated as safety issue: Yes ]
  • Total strokes (intra cranial haemorrhage or ischaemic stroke) within 7 days [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]
  • Major bleeding (other intracranial haemorrhage or ischaemic stroke) [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]

Enrollment: 1005
Study Start Date: November 2007
Estimated Study Completion Date: July 2014
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: group A
tenecteplase (group A)
Drug: tenecteplase (group A)
tenecteplase (group A)
Other Name: tenecteplase (group A)
Placebo Comparator: group B
placebo ( group B)
Drug: placebo ( group B)
placebo ( group B)
Other Name: placebo ( group B)

Detailed Description:

A prospective, randomized, double-blind, placebo-controlled, international, multicentre, parallel-group comparison trial evaluating the efficacy and safety of single i.v. bolus tenecteplase plus standard anticoagulation as compared with standard anticoagulation in normotensive patients with acute pulmonary embolism and with echocardiographic and laboratory evidence of right ventricular dysfunction.Patients suffering from acute pulmonary embolism (first symptoms occurring within 15 days) confirmed by lung scanning or a positive spiral computed tomogram, or a positive pulmonary angiogram, presenting with right ventricular dysfunction on echocardiography and tested troponin I or T positive will be included in the study if they have no exclusion criteria.Patients in the investigational group will receive: Ø Tenecteplase as a single body-weight (known or estimated) adjusted IV bolus administered over 5 - 10 seconds not later than 30 minutes after randomization, and not later than 2 hours after the diagnosis of RV dysfunction Weight (kg) Dose in mg Dose in units Dose in ml<60 30 mg 6000 U 6 ml>60 to <70 35 mg 7000 U 7 ml>70 to <80 40 mg 8000 U 8 ml>80 to <90 45 mg 9000 U 9 ml>90 50 mg 10000 U 10 mlØ and: concomitant therapy-Unfractionated heparin at a dose of 80 IUxKg-1 as an intravenous bolus, followed by an infusion of 18 IUxKg-1xh-1, to be administered immediately after randomization in all patients for at least 48 hours following randomization. Beyond this period, intravenous UFH may be substituted with subcutaneous heparin (LMWH) treatment. The bolus will be omitted when heparin was started before randomisation.Patients in the control group will receive Ø placebo as a single body-weight (known or estimated) adjusted IV bolus administered over 5 - 10 seconds not later than 30 minutes after randomization, and not later than 2 hours after the diagnosis of RV dysfunction. Weight (kg) Dose in ml<60 6 ml>60 to <70 7 ml>70 to <80 8 ml>80 to <90 9 ml>90 10 mlØ and concomitant therapy with Unfractionated heparin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 years or older
  • Acute PE (first symptoms occurring 15 days or less before randomisation) confirmed by lung scan, or a positive spiral computed tomogram, or a positive pulmonary angiogram
  • Right ventricular dysfunction confirmed by echocardiography or spiral computed tomography of the chest and a positive troponin I or T test

Exclusion criteria:

  • Haemodynamic collapse at presentation as defined above
  • Known significant bleeding risk
  • Administration of thrombolytic agents within the previous 4 days
  • Vena cava filter insertion or pulmonary thrombectomy within the previous 4 days
  • Uncontrolled hypertension defined as systolic BP >180 mm Hg and/or diastolic BP >110 mm Hg at randomisation
  • Treatment with an investigational drug under another study protocol in the previous 7 days or greater, according to local requirements
  • Previous enrolment in this study
  • Known hypersensitivity to tenecteplase, alteplase, unfractionated heparin, or to any of the excipients
  • Pregnancy, lactation or parturition within the previous 30 days. Women of childbearing age must have a negative pregnancy test or use a medically accepted method of birth control
  • Known coagulation disorder (including vitamin K antagonists)
  • Any other condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated
  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: NCT00639743

Locations
Austria
Vienna Medical University
Vienne, Austria
Belgium
Hospital St. Luc
Brussels, Belgium
France
CHU Hopital Jean Minjoz
Besançon, France
Germany
Universistaetsklinik
Freiburg, Germany
Greece
Democritus University of Thrace
Alexandroupolis, Greece
Hungary
University of Pécs
Pécs, Hungary
Israel
Rambam Health Care Campus
Haifa, Israel
Italy
Istituto di Cardiologia, Policlinico S.Orsola-MaBologna
Bologna, Italy
Poland
Medical University of Warsaw
Warsaw, Poland
Portugal
Hospital Garcia de Orta
Almada, Portugal
Slovenia
University Medical Center
Ljubljana, Slovenia
Spain
Ramon y Cajal Hospital
Madrid, Spain
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
German Federal Ministry of Education and Research
Boehringer Ingelheim
Investigators
Principal Investigator: Guy MEYER, MD PhD Assistance Publique Hopitaux de Paris - Department of pneumology - European Hospital George Pompidou - Paris 15
Principal Investigator: Stavros Konstantinides, MD, PhD Department of Cardiology and Pulmonolog - Universitaetsmedizin Goettingen - 37099 Goettingen, Germany
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00639743     History of Changes
Other Study ID Numbers: P030444
Study First Received: March 13, 2008
Last Updated: June 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Pulmonary embolism
Heparin
Thrombolytic therapy
Bleeding

Additional relevant MeSH terms:
Embolism
Pulmonary Embolism
Cardiovascular Diseases
Embolism and Thrombosis
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Tenecteplase
Tissue Plasminogen Activator
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014