PEITHO Pulmonary Embolism Thrombolysis Study

NCT00639743 | Completed Phase 3 DMC

• 1 other identifier: P030444
• Study Type: interventional
• Target: 1,005
• Locations: 12 countries
• Sites: 12

Brief Summary

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.

Conditions

Pulmonary Embolism

Keywords

Pulmonary embolism; Heparin; Thrombolytic therapy; Bleeding

Outcome Measures

Primary Outcomes (2)

• Clinical composite endpoint of all-cause mortality or haemodynamic collapse within 7 days

  Day 7

• 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

  Day 7

Secondary Outcomes (6)

• Death within 7 days

  Day 7

• Haemodynamic collapse within 7 days

  Day 7

• Confirmed symptomatic pulmonary embolism recurrence within 7 days

  Day 7

• Death within 30 days

  Day 30

• Total strokes (intra cranial haemorrhage or ischaemic stroke) within 7 days

  Day 7

Study Arms (2)

group A

EXPERIMENTAL

tenecteplase (group A)

Drug: tenecteplase (group A)

group B

PLACEBO COMPARATOR

placebo ( group B)

Drug: placebo ( group B)

Interventions

placebo ( group B) DRUG

placebo ( group B)

group B

tenecteplase (group A) DRUG

tenecteplase (group A)

group A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• German Federal Ministry of Education and Research: collaborator
• Boehringer Ingelheim: collaborator

Study Sites (12)

Vienna Medical University

Vienna, Austria

Location

Hospital St. Luc

Brussels, Belgium

Location

CHU Hopital Jean Minjoz

Besançon, France

Location

Universistaetsklinik

Freiburg im Breisgau, Germany

Location

Democritus University of Thrace

Alexandroupoli, Greece

Location

University of Pécs

Pécs, Hungary

Location

Rambam Health Care Campus

Haifa, Israel

Location

Istituto di Cardiologia, Policlinico S.Orsola-MaBologna

Bologna, Italy

Location

Medical University of Warsaw

Warsaw, Poland

Location

Hospital Garcia de Orta

Almada, Portugal

Location

University Medical Center

Ljubljana, Slovenia

Location

Ramon y Cajal Hospital

Madrid, Spain

Location

Related Publications (5)

• Wan S, Quinlan DJ, Agnelli G, Eikelboom JW. Thrombolysis compared with heparin for the initial treatment of pulmonary embolism: a meta-analysis of the randomized controlled trials. Circulation. 2004 Aug 10;110(6):744-9. doi: 10.1161/01.CIR.0000137826.09715.9C. Epub 2004 Jul 19.

  PMID: 15262836 RESULT

• Zuo Z, Yue J, Dong BR, Wu T, Liu GJ, Hao Q. Thrombolytic therapy for pulmonary embolism. Cochrane Database Syst Rev. 2021 Apr 15;4(4):CD004437. doi: 10.1002/14651858.CD004437.pub6.

  PMID: 33857326 DERIVED

• Konstantinides SV, Vicaut E, Danays T, Becattini C, Bertoletti L, Beyer-Westendorf J, Bouvaist H, Couturaud F, Dellas C, Duerschmied D, Empen K, Ferrari E, Galie N, Jimenez D, Kostrubiec M, Kozak M, Kupatt C, Lang IM, Lankeit M, Meneveau N, Palazzini M, Pruszczyk P, Rugolotto M, Salvi A, Sanchez O, Schellong S, Sobkowicz B, Meyer G. Impact of Thrombolytic Therapy on the Long-Term Outcome of Intermediate-Risk Pulmonary Embolism. J Am Coll Cardiol. 2017 Mar 28;69(12):1536-1544. doi: 10.1016/j.jacc.2016.12.039.

  PMID: 28335835 DERIVED

• Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, Bluhmki E, Bouvaist H, Brenner B, Couturaud F, Dellas C, Empen K, Franca A, Galie N, Geibel A, Goldhaber SZ, Jimenez D, Kozak M, Kupatt C, Kucher N, Lang IM, Lankeit M, Meneveau N, Pacouret G, Palazzini M, Petris A, Pruszczyk P, Rugolotto M, Salvi A, Schellong S, Sebbane M, Sobkowicz B, Stefanovic BS, Thiele H, Torbicki A, Verschuren F, Konstantinides SV; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014 Apr 10;370(15):1402-11. doi: 10.1056/NEJMoa1302097.

  PMID: 24716681 DERIVED

• Steering Committee. Single-bolus tenecteplase plus heparin compared with heparin alone for normotensive patients with acute pulmonary embolism who have evidence of right ventricular dysfunction and myocardial injury: rationale and design of the Pulmonary Embolism Thrombolysis (PEITHO) trial. Am Heart J. 2012 Jan;163(1):33-38.e1. doi: 10.1016/j.ahj.2011.10.003.

  PMID: 22172434 DERIVED

MeSH Terms

Conditions

Pulmonary Embolism; Hemorrhage

Interventions

Tenecteplase

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2008
• First Posted: March 20, 2008
• Study Start: November 16, 2007
• Primary Completion: July 26, 2012
• Study Completion: November 1, 2014
• Last Updated: November 9, 2020

Record last verified: 2020-11

Locations

DE (1); HU (1); ES (1); PL (1); FR (1); GR (1); IT (1); SL (1); AU (1); IL (1); BE (1); PT (1)