Pulmonary Embolism International THrOmbolysis Study-3
PEITHO-3
A Reduced Dose of Thrombolytic Treatment for Patients With Intermediate High-risk Acute Pulmonary Embolism: a Randomized Controled Trial
3 other identifiers
interventional
800
14 countries
98
Brief Summary
In this study, we will assess the efficacy and safety of a reduced dose of thrombolytic therapy given in addition to low-molecular-weight heparin in patients with intermediate-high-risk acute pulmonary embolism. Half of participants will receive thrombolytic treatment, while the other half will receive a placebo.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Aug 2021
Longer than P75 for phase_3
98 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 10, 2020
CompletedFirst Posted
Study publicly available on registry
June 12, 2020
CompletedStudy Start
First participant enrolled
August 4, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 1, 2028
May 16, 2025
May 1, 2025
5.1 years
June 10, 2020
May 14, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Composite of (1) death from any cause or (2) hemodynamic decompensation or (3) objectively confirmed recurrent PE.
30 days
Secondary Outcomes (19)
Fatal or GUSTO severe or life threatening bleeding
30 days
Composite of the primary efficacy endpoint and GUSTO severe or life-threatening bleeding
30 days
All-cause mortality
30 days
PE related death
30 days
Hemodynamic decompensation
30 days
- +14 more secondary outcomes
Study Arms (2)
Alteplase
EXPERIMENTALPlacebo
PLACEBO COMPARATORInterventions
Eligibility Criteria
You may qualify if:
- Age 18 years or older
- Objectively confirmed acute PE with first symptoms occurring 2 weeks or less before randomization. Objective confirmation is based on at least one of the following criteria: (a) at least one segmental ventilation-perfusion mismatch on lung scanning; (b) a spiral computed tomography pulmonary angiography or pulmonary angiography showing a filling defect or an abrupt obstruction of a segmental or more proximal pulmonary artery
- Acute PE confirmed within 24 hours prior to randomization
- Elevated risk of early death, or of hemodynamic collapse, or PE recurrence, indicated by at least one of the following criteria: (a) systolic blood pressure ≤ 110 mm Hg over at least 15 minutes upon enrolment, (b) temporary need for fluid resuscitation and/or treatment with low-dose catecholamines, provided that the patient could be stabilized within 2 hours of admission and maintains SBP of ≥ 90 mmHg and adequate organ perfusion without catecholamine infusion; (c) respiratory rate \> 20/min or oxygen saturation on pulse oximetry SpO2 \<90% o(or partial arterial oxygen pressure \< 60 mm Hg) at rest while breathing room air, (d) documented history of chronic symptomatic heart failure
- Right ventricular dysfunction indicated by RV/LV diameter ratio \>1.0 on echocardiography apical four-chamber or subcostal four-chamber view or on Computed Tomography Pulmonary Angiography (transverse plane)
- Serum troponin I or T concentration above the upper limit of local normal using a high-sensitivity assay
- Ability to randomize the patient within 6 hours after the investigator receives the results of the second of the two criteria for RV dysfunction (RV/LV diameter ratio \>1.0) and myocardial injury (serum troponin I or T concentration above the upper limit of local normal), whichever comes latest.
- Signed informed consent form
You may not qualify if:
- Hemodynamic instability
- Active bleeding
- History of non-traumatic intracranial bleeding, any time
- Acute ischemic stroke or transient ischemic attack (TIA) within the previous 6 months
- Known central nervous system neoplasm/metastasis
- Neurologic, ophthalmologic, abdominal, cardiac, thoracic, vascular or orthopedic surgery or trauma within 3 previous weeks
- Platelet count \< 100 G/L
- INR \> 1.4. If INR not available: prothrombin time ratio \< 60%. If both INR and prothrombin time ratio are measured, INR is relevant for the assessment of this criterion.
- Treatment with antiplatelet agents other than (a) acetylsalicylic acid (ASA) ≤ 100 mg once daily or (b) clopidogrel 75 mg once daily or (c) a single loading dose of ASA or clopidogrel. Dual antiplatelet therapy (ASA + clopidogrel) is not allowed.
- Known pericarditis or endocarditis
- Known significant bleeding risk according to the investigator's judgement
- Administration of thrombolytic agents within the previous 4 days
- Vena cava filter insertion or pulmonary thrombectomy within the previous 4 days
- Current participation in another interventional clinical study
- Previous enrolment in this study
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Assistance Publique - Hôpitaux de Parislead
- Johannes Gutenberg University Mainzcollaborator
- Life Sciences Research Partners (D Collen Research Foundation)collaborator
- Canadian Institutes of Health Research (CIHR)collaborator
- Instituto de Salud Carlos IIIcollaborator
- International Network of VENous Thromboembolism Clinical Research Networkscollaborator
- Boehringer Ingelheimcollaborator
Study Sites (98)
Graz, Mediz Universität
Graz, 8036, Austria
Ordensklinikum Linz GmbH Elisabethinen
Linz, 4020, Austria
UCL Brussels
Brussels, Belgium
KU Leuven
Leuven, 3000, Belgium
CHU Liège
Liège, 4000, Belgium
Foothills Medical Centre
Calgary, Alberta, Canada
Juravinski Hospital - Hamilton Health Sciences Corporation
Hamilton, Ontario, ON L8V 1C3, Canada
Hamilton General Hospital - Hamilton Health Sciences Corporation
Hamilton, Ontario, Canada
Kingston Health Sciences Centre
Kingston, Ontario, Canada
London Health Sciences Centre
London, Ontario, Canada
The Ottawa Hopsital, General and Civic campuses
Ottawa, Ontario, Canada
Jewish General Hospital
Montreal, Quebec, Canada
CHU d'Angers
Angers, 49933, France
CHU de Besançon - Hôpital Jean-Minjoz
Besançon, 25030, France
CHU de Brest - Hôpital de la Cavale Blanche
Brest, 29000, France
CHU de Tours - Hôpital Trousseau
Chambray-lès-Tours, 37170, France
CHU de Clermont-Ferrand - Hôpital Gabriel Montpied
Clermont-Ferrand, 63000, France
AP-HP - hôpital Henri-Mondor
Créteil, 94010, France
CHU de Grenoble - Hôpital Michallon
La Tronche, 38700, France
AP-HP - hôpital Bicêtre
Le Kremlin-Bicêtre, 94270, France
CHU de Lille - Institut Cœur Poumon
Lille, 59000, France
HCL - Hôpital Edouard Herriot
Lyon, 69000, France
HCL - Hôpital Edouard Herriot
Lyon, 69000, France
HCL - Centre Hospitalier Lyon-Sud, Pierre-Bénite
Lyon, 69495, France
AP-HM - Hôpital de la Timone
Marseille, 13000, France
CHU de Montpellier - Hôpital Lapeyronie
Montpellier, 34000, France
CHU de Nice - Hôpital Pasteur
Nice, 06000, France
AP-HP - Hôpital Lariboisière
Paris, 75010, France
AP-HP - hôpital européen Georges-Pompidou
Paris, 75015, France
AP-HP - Hôpital Bichat-Claude-Bernard
Paris, 75018, France
AP-HP - Hôpital Tenon
Paris, 75020, France
HCL - Centre Hospitalier Lyon-Sud
Pierre-Bénite, 69495, France
CHU de Saint-Étienne - Hôpital Nord
Saint-Etienne, 42055, France
CHU de Strasbourg - Hôpital Civil
Strasbourg, 67000, France
CHU de Toulouse - Hôpital Rangueil
Toulouse, 31000, France
Universitäts-Herzzentrum Freiburg - Bad Krozingen
Bad Krozingen, 79189, Germany
DRK Kliniken Berlin Köpenick
Berlin, 10117, Germany
Berlin, DRK Kliniken Westend
Berlin, 14050, Germany
Augustinerinnen Hospital
Cologne, 50678, Germany
Cologne Universität Herzzentrum
Cologne, 50937, Germany
Dresden, Städtisches Klinikum
Dresden, 01067, Germany
Düsseldorf, Augusta-Krankenhaus
Düsseldorf, 40472, Germany
Freiburg Universität
Freiburg im Breisgau, 79085, Germany
Greifswald, Univ.-Medizin
Greifswald, 17489, Germany
Hannover, Medizinische Hochschule Hannover
Hanover, 30625, Germany
Leipzig, Univ.-Klinikum
Leipzig, 4103, Germany
Mainz Universitätsmedizin, CTH
Mainz, 55131, Germany
Mainz, Katholisches Klinikum
Mainz, 55131, Germany
Universitätsmedizin Mannheim UMM
Mannheim, 68167, Germany
Regensburg, Uniklinik
Regensburg, 93053, Germany
Tübingen, Univ.-Klinikum
Tübingen, 72076, Germany
Ulm, Universitätsklinikum
Ulm, 89081, Germany
University Hospital Ancona / Ospedali Riunit
Ancona, 60020, Italy
Spedali Riuniti - Cremona
Cremona, 26100, Italy
Ospedale San Giuseppe - Empoli
Empoli, 50053, Italy
Azienda Ospedaliera Careggi - Firenze
Florence, 50134, Italy
Humanitas Hospital - Milano
Milan, 20089, Italy
University of Perugia
Perugia, 06123, Italy
Ospedale Ca Foncello - Treviso
Treviso, 31100, Italy
Catharina hospital
Eindhoven, Netherlands
Medisch Spectrum Twente
Enschede, Netherlands
Martini hospital
Groningen, Netherlands
Maasstad hospital
Rotterdam, Netherlands
Antonius hospital
Sneek, Netherlands
Haaglanden hospital
The Hague, Netherlands
Isala hospital
Zwolle, Netherlands
Medical University of Bialystok
Bialystok, Poland
Department of Cardiac and Vascular Diseases
Krakow, Poland
Medical University of Lodz
Lodz, Poland
University of Warmia Mazury in Olsztyn - School of Medicine
Olsztyn, 11-041, Poland
Poznan University of Medical Sciences
Poznan, Poland
Medical University of Warsaw
Warsaw, Poland
Hospital Garcia de Orta
Almada, Portugal
Centro Hospitalar de Lisboa Norte/ Hospitalde Santa Maria
Lisbon, Portugal
Centro Hospitalar de Lisboa Ocidental
Lisbon, Portugal
Hospital Pedro Hispano
Matosinhos Municipality, Portugal
Centro Hospitalar do Porto
Porto, Portugal
Centro Hospitalar de Setubal
Setúbal, Portugal
Spitalul Judetean de Urgenta Baia Mare
Baia Mare, 430031, Romania
Bucuresti - Spitalul Clinic de Urgenta Sf. Pantelimon
Bucharest, Romania
Spitalul Judetean de Urgenta Constanta
Constanța, 900591, Romania
Iasi - St Spiridon Emergency Conty Hospital
Iași, 700111, Romania
Institutul de Boli Cardio-Vasculare Timisoara
Timișoara, Romania
Cardiology Clinic, Emergency Center, Clinical Center of Serbia
Belgrade, Serbia
Cardiology Clinic, Clinical Center of Niš
Niš, Serbia
Institute for Lung Diseases of Vojvodina, Sremska Kamenica
Novi Sad, Serbia
University Medical Centre Ljubljana
Ljubljana, 1000, Slovenia
Hospital Germans Trias i Pujol
Badalona, 08916, Spain
Hospital Clinic
Barcelona, 08036, Spain
Hospital Bellvitge
Barcelona, 08907, Spain
Hospital Cartagena
Cartagena, Spain
Hospital Galdakao
Galdakao, 48960, Spain
Clínica Universitaria Navarra
Madrid, 28027, Spain
Hospital Ramón y Cajal
Madrid, 28034, Spain
Hospital Virgen del Rocío
Seville, 41013, Spain
Hospital La Fe
Valencia, 46026, Spain
Geneva University Hospital
Geneva, 1205, Switzerland
Hôpital du Valais
Sion, 1951, Switzerland
Related Publications (5)
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: 24716681BACKGROUNDBarco S, Vicaut E, Klok FA, Lankeit M, Meyer G, Konstantinides SV; PEITHO Investigators. Improved identification of thrombolysis candidates amongst intermediate-risk pulmonary embolism patients: implications for future trials. Eur Respir J. 2018 Jan 18;51(1):1701775. doi: 10.1183/13993003.01775-2017. Print 2018 Jan. No abstract available.
PMID: 29348184BACKGROUNDKonstantinides 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: 28335835BACKGROUNDMarti C, John G, Konstantinides S, Combescure C, Sanchez O, Lankeit M, Meyer G, Perrier A. Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis. Eur Heart J. 2015 Mar 7;36(10):605-14. doi: 10.1093/eurheartj/ehu218. Epub 2014 Jun 10.
PMID: 24917641BACKGROUNDSanchez O, Charles-Nelson A, Ageno W, Barco S, Binder H, Chatellier G, Duerschmied D, Empen K, Ferreira M, Girard P, Huisman MV, Jimenez D, Katsahian S, Kozak M, Lankeit M, Meneveau N, Pruszczyk P, Petris A, Righini M, Rosenkranz S, Schellong S, Stefanovic B, Verhamme P, de Wit K, Vicaut E, Zirlik A, Konstantinides SV, Meyer G; PEITHO-3 Investigators. Reduced-Dose Intravenous Thrombolysis for Acute Intermediate-High-risk Pulmonary Embolism: Rationale and Design of the Pulmonary Embolism International THrOmbolysis (PEITHO)-3 trial. Thromb Haemost. 2022 May;122(5):857-866. doi: 10.1055/a-1653-4699. Epub 2021 Oct 31.
PMID: 34560806BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Olivier SANCHEZ, MD
Assistance Publique - Hôpitaux de Paris
- PRINCIPAL INVESTIGATOR
Stavros Konstantinides, MD
University Medical Center Mainz
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 10, 2020
First Posted
June 12, 2020
Study Start
August 4, 2021
Primary Completion (Estimated)
September 1, 2026
Study Completion (Estimated)
August 1, 2028
Last Updated
May 16, 2025
Record last verified: 2025-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, ICF
- Time Frame
- One year after the last publication
- Access Criteria
- Data sharing must be accepted by the sponsor and the PI based on scientific project and scientific involvement of the PI team. The founder could be involved in the decision. Teams wishing obtain IPD must meet the sponsor and IP team to present scientifics (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractualization.
Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared.