PEITHO Pulmonary Embolism Thrombolysis Study

NCT ID: NCT00639743

Last Updated: 2020-11-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1005 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-16
• Study Completion Date: 2014-11-30

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.

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

Conditions

Pulmonary Embolism

Keywords

Pulmonary embolism; Heparin; Thrombolytic therapy; Bleeding

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

group A

tenecteplase (group A)

Group Type: EXPERIMENTAL

tenecteplase (group A)

Intervention Type: DRUG

tenecteplase (group A)

group B

placebo ( group B)

Group Type: PLACEBO_COMPARATOR

placebo ( group B)

Intervention Type: DRUG

placebo ( group B)

Interventions

placebo ( group B)

placebo ( group B)

Intervention Type: DRUG

tenecteplase (group A)

tenecteplase (group A)

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role: collaborator

Boehringer Ingelheim

INDUSTRY

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guy MEYER, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique Hopitaux de Paris - Department of pneumology - European Hospital George Pompidou - Paris 15

Stavros Konstantinides, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Cardiology and Pulmonolog - Universitaetsmedizin Goettingen - 37099 Goettingen, Germany

Locations

Vienna Medical University

Vienna, , Austria

Hospital St. Luc

Brussels, , Belgium

CHU Hopital Jean Minjoz

Besançon, , France

Universistaetsklinik

Freiburg im Breisgau, , Germany

Democritus University of Thrace

Alexandroupoli, , Greece

University of Pécs

Pécs, , Hungary

Rambam Health Care Campus

Haifa, , Israel

Istituto di Cardiologia, Policlinico S.Orsola-MaBologna

Bologna, , Italy

Medical University of Warsaw

Warsaw, , Poland

Hospital Garcia de Orta

Almada, , Portugal

University Medical Center

Ljubljana, , Slovenia

Ramon y Cajal Hospital

Madrid, , Spain

Countries

Austria; Belgium; France; Germany; Greece; Hungary; Israel; Italy; Poland; Portugal; Slovenia; Spain

References

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.

Reference Type: RESULT

PMID: 15262836 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33857326 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28335835 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24716681 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22172434 (View on PubMed)

Other Identifiers

P030444

Identifier Type: -

Identifier Source: org_study_id