Pulmonary EmbolismPhase 3PEITHO-3NCT04430569
Pulmonary Embolism International THrOmbolysis Study-3
A Phase 3 study testing Alteplase in people with Pulmonary Embolism, run by Assistance Publique - Hôpitaux de Paris at 85 sites in 14 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Embolism
- What is being tested?
- Alteplase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 800 participants
- Where
- 85 sitesin 14 countries
- Study dates
- 4 Aug 2021to Mar 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 28Show fewer
- 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.
- Any direct oral anticoagulant within 12 hours of inclusion
- Uncontrolled hypertension defined by SBP > 180 mm Hg at the time of inclusion
- 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
- Known hypersensitivity to alteplase, gentamicin (a residue of the Actilyse® manufacturing process present in trace amounts), any of the excipients of Actilyse®, or low-molecular weight heparin (LMWH)
- Known previous immune heparin-induced thrombocytopenia
- Known severe liver disease (grade ≥ 3) including liver failure, cirrhosis, portal hypertension (esophageal varices) and active hepatitis
- Acute symptomatic pancreatitis
- Gastrointestinal ulcers or esophageal varices, documented within the past 3 months
- Known arterial aneurysm, arterial or venous malformations
- Pregnancy or parturition within the previous 30 days or current breastfeeding.
- Women of childbearing potential who do not have a negative pregnancy test at the inclusion visit and do not use one of the following methods of birth control: hormonal contraception or intrauterine device or bilateral tubal occlusion
- Any other condition that the investigator feels would place the patient at increased risk upon start of the investigational treatment
- Life expectancy of less than 6 months or inability to complete 6-month follow-up.
- Patient under legal protection
Trial locations and contacts
85 sites in 14 countries.
85 sites in 14 countries
France18 sites
CHU d'Angers
Angers, 49933
CHU de Besançon - Hôpital Jean-Minjoz
Besançon, 25030
CHU de Brest - Hôpital de la Cavale Blanche
Brest, 29000
CHU de Tours - Hôpital Trousseau
Chambray-lès-Tours, 37170
CHU de Clermont-Ferrand - Hôpital Gabriel Montpied
Clermont-Ferrand, 63000
AP-HP - hôpital Henri-Mondor
Créteil, 94010
CHU de Grenoble - Hôpital Michallon
La Tronche, 38700
AP-HP - hôpital Bicêtre
Le Kremlin-Bicêtre, 94270
HCL - Hôpital Edouard Herriot
Lyon, 69000
HCL - Centre Hospitalier Lyon-Sud, Pierre-Bénite
Lyon, 69495
AP-HM - Hôpital de la Timone
Marseille, 13000
CHU de Nice - Hôpital Pasteur
Nice, 06000
AP-HP - hôpital européen Georges-Pompidou
Paris, 75015
AP-HP - Hôpital Bichat-Claude-Bernard
Paris, 75018
AP-HP - Hôpital Tenon
Paris, 75020
CHU de Saint-Étienne - Hôpital Nord
Saint-Etienne, 42055
CHU de Strasbourg - Hôpital Civil
Strasbourg, 67000
CHU de Toulouse - Hôpital Rangueil
Toulouse, 31000
Germany15 sites
Universitäts-Herzzentrum Freiburg - Bad Krozingen
Bad Krozingen, 79189
DRK Kliniken Berlin Köpenick
Berlin, 10117
Augustinerinnen Hospital
Cologne, 50678
Cologne Universität Herzzentrum
Cologne, 50937
Dresden, Städtisches Klinikum
Dresden, 01067
Düsseldorf, Augusta-Krankenhaus
Düsseldorf, 40472
Freiburg Universität
Freiburg im Breisgau, 79085
Greifswald, Univ.-Medizin
Greifswald, 17489
Hannover, Medizinische Hochschule Hannover
Hanover, 30625
Leipzig, Univ.-Klinikum
Leipzig, 4103
Mainz Universitätsmedizin, CTH
Mainz, 55131
Mainz, Katholisches Klinikum
Mainz, 55131
Universitätsmedizin Mannheim UMM
Mannheim, 68167
Tübingen, Univ.-Klinikum
Tübingen, 72076
Ulm, Universitätsklinikum
Ulm, 89081
Spain8 sites
Hospital Germans Trias i Pujol
Badalona, 08916
Hospital Clinic
Barcelona, 08036
Hospital Bellvitge
Barcelona, 08907
Hospital Cartagena
Cartagena
Hospital Galdakao
Galdakao, 48960
Hospital Ramón y Cajal
Madrid, 28034
Hospital Virgen del Rocío
Seville, 41013
Hospital La Fe
Valencia, 46026
Canada7 sites
Foothills Medical Centre
Calgary, Alberta
Juravinski Hospital - Hamilton Health Sciences Corporation
Hamilton, Ontario, ON L8V 1C3
Hamilton General Hospital - Hamilton Health Sciences Corporation
Hamilton, Ontario
Kingston Health Sciences Centre
Kingston, Ontario
London Health Sciences Centre
London, Ontario
Jewish General Hospital
Montreal, Quebec
The Ottawa Hopsital, General and Civic campuses
Ottawa, Ontario
Italy7 sites
University Hospital Ancona / Ospedali Riunit
Ancona, 60020
Spedali Riuniti - Cremona
Cremona, 26100
Ospedale San Giuseppe - Empoli
Empoli, 50053
Azienda Ospedaliera Careggi - Firenze
Florence, 50134
Humanitas Hospital - Milano
Milan, 20089
University of Perugia
Perugia, 06123
Ospedale Ca Foncello - Treviso
Treviso, 31100
Netherlands7 sites
Catharina hospital
Eindhoven
Medisch Spectrum Twente
Enschede
Martini hospital
Groningen
Maasstad hospital
Rotterdam
Antonius hospital
Sneek
Haaglanden hospital
The Hague
Isala hospital
Zwolle
Portugal6 sites
Hospital Garcia de Orta
Almada
Centro Hospitalar de Lisboa Norte/ Hospitalde Santa Maria
Lisbon
Centro Hospitalar de Lisboa Ocidental
Lisbon
Hospital Pedro Hispano
Matosinhos Municipality
Centro Hospitalar do Porto
Porto
Centro Hospitalar de Setubal
Setúbal
Romania5 sites
Spitalul Judetean de Urgenta Baia Mare
Baia Mare, 430031
Bucuresti - Spitalul Clinic de Urgenta Sf. Pantelimon
Bucharest
Spitalul Judetean de Urgenta Constanta
Constanța, 900591
Iasi - St Spiridon Emergency Conty Hospital
Iași, 700111
Institutul de Boli Cardio-Vasculare Timisoara
Timișoara
Belgium3 sites
UCL Brussels
Brussels
KU Leuven
Leuven, 3000
CHU Liège
Liège, 4000
Serbia3 sites
Cardiology Clinic, Emergency Center, Clinical Center of Serbia
Belgrade
Cardiology Clinic, Clinical Center of Niš
Niš
Institute for Lung Diseases of Vojvodina, Sremska Kamenica
Novi Sad
Poland2 sites
Medical University of Bialystok
Bialystok
University of Warmia Mazury in Olsztyn - School of Medicine
Olsztyn, 11-041
Switzerland2 sites
Geneva University Hospital
Geneva, 1205
Hôpital du Valais
Sion, 1951
About this study
Official title: A Reduced Dose of Thrombolytic Treatment for Patients With Intermediate High-risk Acute Pulmonary Embolism: a Randomized Controled Trial
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.
Read the detailed description
In patients with intermediate-risk pulmonary embolism, full-dose thrombolytic treatment was associated with a reduction in the combined risk of hemodynamic instability or death but was also associated with an increased risk of major and intracranial bleeding. Previous studies suggest that reduced dose of thrombolytic treatment may be as effective as the full dosage, but with a decreased risk of life-threatening bleeding. In this study, we will assess the efficacy and safety of a reduced dosage of thrombolytic therapy in patients with intermediate-high-risk acute pulmonary embolism.
The study is a randomized, placebo-controlled, double blind, multicenter, multinational trial with long-term follow-up.
Patients fulfilling the inclusion criteria and without any of the exclusion criteria will be randomized within 6 hours after the investigator had confirmed the diagnosis.
Patients will receive:
- Alteplase (if randomized in the experimental group) or placebo (if randomized in the reference group) given within 30 minutes of randomization as a 15 min intravenous infusion at a dosage of 0.6 mg/kg with a total dose not exceeding 50 mg.
- Parenteral anticoagulation with low molecular weight heparin, unfractionnated heparin or fondaparinux
Primary objective is to assess the efficacy of reduced dose thrombolytic therapy in patients with acute intermediate-high-risk pulmonary embolism at day 30.
Secondary objectives are:
- To assess the safety of reduced dose thrombolytic therapy in patients with intermediate-high-risk acute pulmonary embolism at day 30
- To assess the net clinical benefit of reduced dose thrombolytic therapy in patients with intermediate-high-risk acute pulmonary embolism at day 30
- To assess the effect of reduced dose thrombolytic therapy on overall mortality of patients with intermediate-high-risk acute pulmonary embolism at day 30
- To assess the effect of reduced dose thrombolytic therapy on long-term mortality, functional impairment, residual right ventricular dysfunction and chronic thromboembolic pulmonary hypertension at 6 months and 2 years
- To assess the effect of reduced-dose thrombolytic therapy on utilization of health care resources at day 30 and day 180
- Conditions
- Pulmonary Embolism
- Being tested
- Alteplase, Placebo
- Keywords
- Intermediate-high-risk acute pulmonary embolism, Thrombolysis
- Medical subject headings
- Pulmonary Embolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlteplaseDrug
Alteplase single intravenous infusion of 0.6 mg/kg of estimated bodyweight with a maximum of 50 mg given over 15 minutes.
PlaceboDrug
Placebo single intravenous infusion of 0.6 mg/kg of estimated bodyweight with a maximum of 50 mg given over 15 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Alteplase | Experimental | Not described Receives: Drug: Alteplase |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite of (1) death from any cause or (2) hemodynamic decompensation or (3) objectively confirmed recurrent PE.
Measured: 30 days
Secondary outcomes (19)
Fatal or GUSTO severe or life threatening bleeding
Measured: 30 days
Composite of the primary efficacy endpoint and GUSTO severe or life-threatening bleeding
Assessment of net clinical benefit
Measured: 30 days
All-cause mortality
Measured: 30 days
PE related death
Measured: 30 days
Hemodynamic decompensation
Measured: 30 days
Recurrent PE
Measured: 30 days
Need for rescue thrombolysis, catheter-directed treatment or surgical embolectomy
Measured: 30 days
Ischemic or hemorrhagic stroke
Measured: 30 days
Serious adverse events
Measured: 30 days
Persisting dyspnea
Measured: 180 days
Persisting dyspnea
Measured: 2 years
Persistent right ventricular dysfunction
Measured: 180 days
Persistent right ventricular dysfunction
Measured: 2 years
Functional outcome
Measured: 180 days
Functional outcome
Measured: 2 years
All-cause mortality
Measured: 2 years
Confirmed chronic thromboembolic pulmonary hypertension
Measured: 2 years
Utilization of health care ressources
Questionnaire assessing the impact of the treatment on utilization of health care ressources
Measured: 30 days
Utilization of health care ressources
Questionnaire assessing the impact of the treatment on utilization of health care ressources
Measured: 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2020
- Study start4 Aug 2021
- Primary completion13 Apr 2026
- Study completionMar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Pulmonary EmbolismStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Johannes Gutenberg University Mainz, Life Sciences Research Partners (D Collen Research Foundation), Canadian Institutes of Health Research (CIHR), Instituto de Salud Carlos III, International Network of VENous Thromboembolism Clinical Research Networks, Boehringer Ingelheim
- Responsible party
- Sponsor
- Investigators
- Olivier SANCHEZ, MD, Principal investigator, Assistance Publique - Hôpitaux de ParisStavros Konstantinides, MD, Principal investigator, University Medical Center Mainz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04430569
- Sponsor's protocol ID
- P160924
- Other IDs
- P160924, PHRCN-16-0580, 2018-000816-96, 2018
- Acronym
- PEITHO-3
- Status last verified
- Jun 2026
- First submitted
- 10 Jun 2020
- Last updated
- 1 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared.
Publications
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.
PubMed 24716681Barco 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.
PubMed 29348184Konstantinides 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.
PubMed 28335835Marti 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.
PubMed 24917641Sanchez 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.
PubMed 34560806
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Reduced Dose of Thrombolytic Treatment for Patients With Intermediate High-risk Acute Pulmonary Embolism: a Randomized Controled Trial
- ClinicalTrials.gov ID
- NCT04430569
- Acronym / sponsor ID
- PEITHO-3 / P160924
- Conditions
- Pulmonary Embolism
- Keywords
- Intermediate-high-risk acute pulmonary embolism, Thrombolysis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 800 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Johannes Gutenberg University Mainz, Life Sciences Research Partners (D Collen Research Foundation), Canadian Institutes of Health Research (CIHR), Instituto de Salud Carlos III, International Network of VENous Thromboembolism Clinical Research Networks, Boehringer Ingelheim
- Study start
- 4 Aug 2021 (actual)
- Primary completion
- 13 Apr 2026 (actual)
- Study completion
- Mar 2028 (estimated)
- First posted
- 12 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In patients with intermediate-risk pulmonary embolism, full-dose thrombolytic treatment was associated with a reduction in the combined risk of hemodynamic instability or death but was also associated with an increased risk of major and intracranial bleeding. Previous studies suggest that reduced dose of thrombolytic treatment may be as effective as the full dosage, but with a decreased risk of life-threatening bleeding. In this study, we will assess the efficacy and safety of a reduced dosage of thrombolytic therapy in patients with intermediate-high-risk acute pulmonary embolism.
The study is a randomized, placebo-controlled, double blind, multicenter, multinational trial with long-term follow-up.
Patients fulfilling the inclusion criteria and without any of the exclusion criteria will be randomized within 6 hours after the investigator had confirmed the diagnosis.
Patients will receive:
- Alteplase (if randomized in the experimental group) or placebo (if randomized in the reference group) given within 30 minutes of randomization as a 15 min intravenous infusion at a dosage of 0.6 mg/kg with a total dose not exceeding 50 mg.
- Parenteral anticoagulation with low molecular weight heparin, unfractionnated heparin or fondaparinux
Primary objective is to assess the efficacy of reduced dose thrombolytic therapy in patients with acute intermediate-high-risk pulmonary embolism at day 30.
Secondary objectives are:
- To assess the safety of reduced dose thrombolytic therapy in patients with intermediate-high-risk acute pulmonary embolism at day 30
- To assess the net clinical benefit of reduced dose thrombolytic therapy in patients with intermediate-high-risk acute pulmonary embolism at day 30
- To assess the effect of reduced dose thrombolytic therapy on overall mortality of patients with intermediate-high-risk acute pulmonary embolism at day 30
- To assess the effect of reduced dose thrombolytic therapy on long-term mortality, functional impairment, residual right ventricular dysfunction and chronic thromboembolic pulmonary hypertension at 6 months and 2 years
- To assess the effect of reduced-dose thrombolytic therapy on utilization of health care resources at day 30 and day 180
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alteplase | Experimental | Drug: Alteplase |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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)
Key exclusion criteria (28 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlteplaseAlteplase single intravenous infusion of 0.6 mg/kg of estimated bodyweight with a maximum of 50 mg given over 15 minutes. | Drug | Alteplase |
| PlaceboPlacebo single intravenous infusion of 0.6 mg/kg of estimated bodyweight with a maximum of 50 mg given over 15 minutes. | Drug | Placebo |
Primary outcome
Composite of (1) death from any cause or (2) hemodynamic decompensation or (3) objectively confirmed recurrent PE.
Time frame: 30 days
19 secondary outcomes
Fatal or GUSTO severe or life threatening bleeding
Time frame: 30 days
Composite of the primary efficacy endpoint and GUSTO severe or life-threatening bleeding
Time frame: 30 days
All-cause mortality
Time frame: 30 days
PE related death
Time frame: 30 days
Hemodynamic decompensation
Time frame: 30 days
Recurrent PE
Time frame: 30 days
Need for rescue thrombolysis, catheter-directed treatment or surgical embolectomy
Time frame: 30 days
Ischemic or hemorrhagic stroke
Time frame: 30 days
Serious adverse events
Time frame: 30 days
Persisting dyspnea
Time frame: 180 days
Persisting dyspnea
Time frame: 2 years
Persistent right ventricular dysfunction
Time frame: 180 days
Persistent right ventricular dysfunction
Time frame: 2 years
Functional outcome
Time frame: 180 days
Functional outcome
Time frame: 2 years
All-cause mortality
Time frame: 2 years
Confirmed chronic thromboembolic pulmonary hypertension
Time frame: 2 years
Utilization of health care ressources
Time frame: 30 days
Utilization of health care ressources
Time frame: 180 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2026.
- Background: PubMed 24716681Meyer 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.
- Background: PubMed 29348184Barco 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.
- Background: PubMed 28335835Konstantinides 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.
- Background: PubMed 24917641Marti 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.
- Background: PubMed 34560806Sanchez 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.
- Individual participant dataSharing planned: Yes. Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olivier SANCHEZ, MD principal investigator
Assistance Publique - Hôpitaux de Paris
Stavros Konstantinides, MD principal investigator
University Medical Center Mainz
85 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Alteplase in people with Pulmonary Embolism, run by Assistance Publique - Hôpitaux de Paris at 85 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 85 sites in France, Germany, Spain, Canada, Italy and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite of (1) death from any cause or (2) hemodynamic decompensation or (3) objectively confirmed recurrent PE. (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04430569, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2026.