Clinical trial • Phase III • Cardiology

ALTEPLASE for Intermediate-high-risk acute pulmonary embolism | Pulmonary embolism

Phase III trial of ALTEPLASE for Intermediate-high-risk acute pulmonary embolism | Pulmonary embolism.

Overview

Trial Therapeutic Area
Cardiology
Trial Disease
Intermediate-high-risk acute pulmonary embolism | Pulmonary embolism
Trial Stage
Phase III
Drug Modality
Peptide/protein/enzyme

Key dates

Initial CTIS Submission Date
06-05-2024
First CTIS Authorization Date
17-06-2024

Trial design

Randomised, placebo arm: actilyse 50mg placebo; active arm: reduced-dose alteplase (actilyse, active substance alteplase) administered intravenously (maximum total dose shown = 50 mg). detailed dosing schedule not specified in provided json.-controlled Phase III trial in Netherlands, Austria, Germany and others.

Randomised
Yes
Comparator
Placebo arm: ACTILYSE 50mg placebo; Active arm: reduced-dose alteplase (ACTILYSE, active substance alteplase) administered intravenously (maximum total dose shown = 50 mg). Detailed dosing schedule not specified in provided JSON.
Target Sample Size
760
Trial Duration For Participant
730

Eligibility

Recruits 760 No vulnerable populations selected (isVulnerablePopulationSelected=false). Patients under legal protection are explicitly excluded. Participants must be adults (Age ≥ 18) and provide a signed informed consent form; no assent provisions for minors are applicable because minors are excluded..

Pregnancy Exclusion
Pregnancy or parturition within the previous 30 days or current breastfeeding.
Vulnerable Population
No vulnerable populations selected (isVulnerablePopulationSelected=false). Patients under legal protection are explicitly excluded. Participants must be adults (Age ≥ 18) and provide a signed informed consent form; no assent provisions for minors are applicable because minors are excluded.

Inclusion criteria

  • {"criterion_text":"- Age 18 years or older"}
  • {"criterion_text":"- 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 computed tomography pulmonary angiography (CTPA) or selective pulmonary angiography showing a filling defect or an abrupt obstruction of a segmental or more proximal pulmonary artery;"}
  • {"criterion_text":"- Acute PE confirmed within 24 hours prior to randomization;"}
  • {"criterion_text":"- Elevated risk of early death, or of hemodynamic collapse, or PE recurrence, indicated by at least one of the following criteria:  systolic blood pressure ≤ 110 mm Hg over at least 15 minutes upon enrolment  temporary need for fluid resuscitation and/or treatment with low dose catecholamines because of arterial hypotension at presentation, provided that the patient could be stabilized within 2 hours of admission and maintains SBP of ≥ 90 mm Hg and adequate organ perfusion without catecholamine infusion  respiratory rate > 20/min or oxygen saturation on pulse oximetry (SpO2) < 90% (or partial arterial oxygen pressure < 60 mm Hg) at rest while breathing room air  documented history of chronic symptomatic heart failure, defined as previous diagnosis of heart failure (i.e. heart failure with reduced, moderately reduced or preserved ejection fraction) or treatment for heart failure at any time during the past 12 months;"}
  • {"criterion_text":"- RV dysfunction indicated by RV/LV diameter ratio > 1.0 on echocardiography apical four-chamber or subcostal four-chamber view or on CTPA (transverse plane);"}
  • {"criterion_text":"- Serum troponin I or T concentration above the upper limit of local normal using a high sensitivity assay"}
  • {"criterion_text":"- Ability to randomize the patient within 6 hours after the investigator receives the result 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 the latest."}
  • {"criterion_text":"- Signed informed consent form."}
  • {"criterion_text":"- [France] Patient insured under a social security system"}

Exclusion criteria

  • {"criterion_text":"- Hemodynamic instability, defined by at least one of the following criteria [1] - cardiac arrest; - obstructive shock, defined as: (i) systolic BP < 90 mm Hg, or vasopressors required to achieve a SBP ≥90 mm Hg despite an adequate filling status; and (ii) end-organ hypoperfusion (altered mental status; cold, clammy skin; oliguria/anuria; increased serum lactate); - isolated persistent hypotension (systolic BP < 90 mm Hg, or a systolic pressure drop ≥ 40 mm Hg for > 15 min), if not caused by new-onset arrhythmia, hypovolemia, or sepsis"}
  • {"criterion_text":"- Previous enrolment in this study"}
  • {"criterion_text":"- Known hypersensitivity to alteplase, gentamicin (a residue of the Actilyse®/Activase® (only for Canada) manufacturing process present in trace amounts), any of the excipients of Actilyse®/Activase® (only for Canada), or low-molecular weight heparin"}
  • {"criterion_text":"- Any direct oral anticoagulant within 12 hours of inclusion"}
  • {"criterion_text":"- Uncontrolled hypertension defined by SBP > 180 mm Hg at the time of inclusion"}
  • {"criterion_text":"- Known pericarditis or endocarditis"}
  • {"criterion_text":"- Active bleeding"}
  • {"criterion_text":"- History of non-traumatic intracranial bleeding, any time"}
  • {"criterion_text":"- Acute ischemic stroke or transient ischemic attack (TIA) within the previous 6 months"}
  • {"criterion_text":"- Known central nervous system neoplasm/metastasis"}
  • {"criterion_text":"- Neurologic, ophthalmologic, abdominal, cardiac, thoracic, vascular or orthopedic surgery or trauma within the previous 3 weeks"}
  • {"criterion_text":"- Platelet count < 100 x 109/L"}
  • {"criterion_text":"- Known previous immune heparin-induced thrombocytopenia"}
  • {"criterion_text":"- Known severe liver disease (grade ≥ 3)1 including liver failure, cirrhosis, portal hypertension (esophageal varices) and active hepatitis"}
  • {"criterion_text":"- Acute symptomatic pancreatitis"}
  • {"criterion_text":"- Gastrointestinal ulcers or esophageal varices, documented within the past 3 months"}
  • {"criterion_text":"- Known arterial aneurysm, arterial or venous malformations"}
  • {"criterion_text":"- Pregnancy or parturition within the previous 30 days or current breastfeeding."}
  • {"criterion_text":"- 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"}
  • {"criterion_text":"- Any other condition that in the investigator’s opinion would place the patient at increased risk upon start of the investigational treatment"}
  • {"criterion_text":"- Life expectancy of less than 6 months or inability to complete 6-month follow-up."}
  • {"criterion_text":"- Patient under legal protection"}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- 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 anti-platelet therapy (ASA + clopidogrel) is not allowed."}
  • {"criterion_text":"- Known significant bleeding risk according to the investigator’s judgement"}
  • {"criterion_text":"- Administration of thrombolytic agents within the previous 4 days"}
  • {"criterion_text":"- Vena cava filter insertion or pulmonary thrombectomy within the previous 4 days"}
  • {"criterion_text":"- [Italy and the Netherlands] Participation in another interventional clinical study within 30 days from the inclusion"}
  • {"criterion_text":"- [All countries except Italy and the Netherlands] Current participation in another interventional clinical study"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The primary outcome is the composite of (1) death from any cause, or (2) hemodynamic decompensation, or (3) objectively confirmed recurrent PE at day 30.","definition_or_measurement_approach":"Composite endpoint assessed at day 30 consisting of: death from any cause; hemodynamic decompensation (as a component of the composite; no further definition in provided JSON); objectively confirmed recurrent pulmonary embolism. Measurement timing: day 30."}

Secondary endpoints

  • {"endpoint_text":"- Fatal or GUSTO severe or life-threatening bleeding within 30 days","definition_or_measurement_approach":"Bleeding classified by GUSTO criteria assessed within 30 days."}
  • {"endpoint_text":"- Net clinical benefit defined as the composite of the primary efficacy outcome and GUSTO severe or life-threatening bleeding within 30 days","definition_or_measurement_approach":"Composite of the primary efficacy outcome (see primary endpoint) and GUSTO severe or life‑threatening bleeding within 30 days."}
  • {"endpoint_text":"- All-cause mortality within 30 days","definition_or_measurement_approach":"Death from any cause assessed at 30 days."}

Recruitment

Planned Sample Size
760
Recruitment Window Months
84
Consent Approach
Written informed consent required (principal inclusion: 'Signed informed consent form.'). Participants are adults (≥18 years). Subject information and ICF documents are provided for adults in multiple languages (documents available for NL, EN, FR, DE, SP, PL, IT, SL as present in published ICF/SIS files). No assent for minors (minors excluded).

Geography

Total Number Of Sites
55
Total Number Of Participants
760

Netherlands

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
14-04-2025
Processing Time Days
319
Number Of Sites
2
Number Of Participants
5

Sites

Site Name
Radboud universitair medisch centrum Stichting
Department Name
Internal Medicine Department, Vascular Medicine
Contact Person Name
Jenneke Leentjens
Site Name
Maasstad Ziekenhuis Stichting
Department Name
Internal Medicine and Hematology
Contact Person Name
Reinier SPRENGER

Austria

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
28-04-2025
Processing Time Days
333
Number Of Sites
2
Number Of Participants
5

Sites

Site Name
Ordensklinikum Linz GmbH
Department Name
2nd Internal Department - Cardiology, Angiology & Internal Intensive Care Medicine
Contact Person Name
Regina Steringer-Mascherbauer
Site Name
Ordensklinikum Linz GmbH
Department Name
Internal Medicine II
Contact Person Name
Johannes Neumeister

Germany

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
31-03-2025
Processing Time Days
304
Number Of Sites
14
Number Of Participants
175

Sites

Site Name
Herzzentrum Leipzig GmbH
Department Name
Cardiology Clinic
Contact Person Name
Holger Thiele
Site Name
DRK Kliniken Berlin
Department Name
Clinic for Internal Medicine - Cardiology
Contact Person Name
Dirk Habedank
Site Name
Medical Center - University Of Freiburg
Department Name
Clinic for Cardiology and Angiology I
Contact Person Name
Christoph Benedikt Olivier
Site Name
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
Department Name
Center for Thrombosis and Hemostasis
Contact Person Name
Stavros Konstantinides
Site Name
Universitaetsklinikum Leipzig AöR
Department Name
Interdisciplinary Internal Intensive Care Medicine
Contact Person Name
Sirak Petros
Site Name
Marienhaus Klinikum Mainz GmbH
Department Name
Cardiology
Contact Person Name
Sabine Genth-Zotz
Site Name
Augustinerinnen Krankenhaeuser gGmbH
Department Name
Cardiology and Internal Intensive Care Medicine
Contact Person Name
Ingo Ahrens
Site Name
Universitaetsmedizin Greifswald KöR
Department Name
Clinic and Polyclinic for Internal Medicine B
Contact Person Name
Alexander Heine
Site Name
Staedtisches Klinikum Dresden
Department Name
2nd Medical Clinic
Contact Person Name
Sebastian Schellong
Site Name
Medizinische Hochschule Hannover
Department Name
Clinic for Pneumology
Contact Person Name
Marius Hoeper
Contact Person Email
hoeper.marius@mh-hannover.de
Site Name
Klinikum Nuernberg
Department Name
Clinic for Internal Medicine 3
Contact Person Name
Joachim Ficker
Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
Internal Medicine III
Contact Person Name
Tobias Geisler
Site Name
Universitat Heidelberg
Department Name
I. Clinique médicale
Contact Person Name
Ibrahim Akin
Contact Person Email
ibrahim.akin@umm.de
Site Name
Medical Center - University Of Freiburg (Bad Krozingen)
Department Name
Clinique de cardiologie et d'angiologie
Contact Person Name
Philipp Breitbart

France

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
27-03-2025
Processing Time Days
300
Number Of Sites
15
Number Of Participants
440

Sites

Site Name
Assistance Publique Hopitaux De Paris
Department Name
Cardiologie
Principal Investigator Name
Prof. Olivier SANCHEZ
Principal Investigator Email
olivier.sanchez@aphp.fr
Contact Person Name
Grégory Ducrocq
Contact Person Email
gregory.ducrocq@aphp.fr
Site Name
Centre Hospitalier Universitaire Grenoble Alpes
Department Name
Cardiologie
Contact Person Name
Hélène Bouvaist
Contact Person Email
hbouvaist@chu-grenoble.fr
Site Name
Centre Hospitalier Universitaire De Saint Etienne
Department Name
Médecin vasculaire et thérapeutique
Contact Person Name
Laurent Bertoletti
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Réanimation et URC Médico-Chirurgicale
Contact Person Name
Aude Gibelin
Contact Person Email
aude.gibelin@aphp.fr
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Chirurgie vasculaire
Contact Person Name
Gabrielle Sarlon-Bartoli
Contact Person Email
gabrielle.sarlon@ap-hm.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Pneumologie
Contact Person Name
Laurent Savale
Contact Person Email
laurent.savale@aphp.fr
Site Name
Centre Hospitalier Regional Et Universitaire De Brest
Department Name
Pneumologie
Contact Person Name
Francis Couturaud
Contact Person Email
francis.couturaud@chu-brest.fr
Site Name
Hospices Civils De Lyon
Department Name
Unité d'anesthésie
Contact Person Name
Donatien De Marignan
Site Name
Besancon University Hospital Center
Department Name
Cardiologie
Contact Person Name
Nicolas Meneveau
Site Name
University Hospital Of Clermont-Ferrand
Department Name
Accueil des Urgences
Contact Person Name
Jeannot Schmidt
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Pneumologie, soins intensifs et endoscopies bronchiques
Principal Investigator Name
Prof. Olivier SANCHEZ
Principal Investigator Email
olivier.sanchez@aphp.fr
Contact Person Name
Olivier Sanchez
Contact Person Email
olivier.sanchez@aphp.fr
Site Name
Centre Hospitalier Universitaire D'Angers
Department Name
Urgences adultes
Contact Person Name
Pierre-Marie Roy
Contact Person Email
pmroy@chu-angers.fr
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Unité de Soins Intensifs en cardiologie
Contact Person Name
Caroline Biendel-Piquet
Contact Person Email
biendel.c@chu-toulouse.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Cardiologie
Contact Person Name
Pascal Lim
Contact Person Email
pascal.lim@aphp.fr
Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
Cardiologie
Contact Person Name
Patrick Ohlmann

Spain

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
27-03-2025
Processing Time Days
300
Number Of Sites
9
Number Of Participants
45

Sites

Site Name
Hospital De Galdakao Usansolo
Department Name
Neumology
Contact Person Name
Aitor BALLAZ-QUINCOCES
Contact Person Email
aitorballaz@gmail.com
Site Name
General University Hospital Santa Lucia
Department Name
Internal Medicine
Contact Person Name
Javier TRUJILLO-SANTOS
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Pneumology
Contact Person Name
Raquel LOPEZ REYES
Contact Person Email
raquel.lopez@separ.es
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Respiratory Department
Contact Person Name
David JIMENEZ
Contact Person Email
djimenez.hrc@gmail.com
Site Name
Bellvitge University Hospital
Department Name
Internal Medicine
Contact Person Name
Antoni RIERA-MESTRE
Contact Person Email
ariera@bellvitgehospital.cat
Site Name
Hospital Germans Trias I Pujol
Department Name
Pneumology
Contact Person Name
Juan José NUNEZ-LOPEZ
Contact Person Email
juanjolopezn@gmail.com
Site Name
Hospital Clinic De Barcelona
Department Name
Respiratory Department
Contact Person Name
Jorge MOISES-LAFUENTE
Contact Person Email
JRMOISES@clinic.cat
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Pneumology
Contact Person Name
Remedios OTERO-CANDELERA
Contact Person Email
rotero@separ.es
Site Name
Hospital Universitario Rio Hortega
Department Name
Intensive Medicine
Contact Person Name
Virginia FRAILE
Contact Person Email
vicky_uvi@yahoo.es

Poland

Earliest CTIS Part Ii Submission Date
02-07-2024
Latest Decision Or Authorization Date
22-04-2025
Processing Time Days
294
Number Of Sites
3
Number Of Participants
25

Sites

Site Name
Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego
Department Name
Department Internal Medicine Hypertension and Angiology
Contact Person Name
Piotr PRUSZCZYK
Contact Person Email
piotr.pruszczyk@wum.edu.pl
Site Name
Uniwersytecki Szpital Kliniczny W Bialymstoku
Department Name
Department of Cardiology
Contact Person Name
Katarzyna PTASZYNSKA
Contact Person Email
kasia.ptaszynska@op.pl
Site Name
Uniwersytecki Szpital Kliniczny W Olsztynie
Department Name
Department of Cardiology and Internal Diseases
Contact Person Name
Leszek GROMADZINSKI
Contact Person Email
lgol@op.pl

Italy

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
28-03-2025
Processing Time Days
301
Number Of Sites
9
Number Of Participants
55

Sites

Site Name
Azienda Socio Sanitaria Territoriale Dei Sette Laghi
Department Name
Dipartimento Emergenza
Contact Person Name
Marco Paolo DONADINI
Site Name
Humanitas Research Hospital
Department Name
Cardiovascular Department Centro Trombosi e Malattie Emorragiche
Contact Person Name
Corrado LODIGIANI
Contact Person Email
corrado.lodigiani@humanitas.it
Site Name
Azienda Ulss 5 Polesana
Department Name
Cardiology department
Contact Person Name
Claudio PICARIELLO
Site Name
Azienda Unita Locale Socio Sanitaria N. 2 Marca Trevigiana
Department Name
UOS “Area Critica” presso U.O.C. Pronto Soccorso e Medicina Generale d'Urgenza
Contact Person Name
Enrico BERNARDI
Contact Person Email
protocollo.aulss2@pecveneto.it
Site Name
Careggi University Hospital
Department Name
SOC Medicina e Chirurgia d'urgenza e Accettazione Trauma Center - Pronto Soccorso
Contact Person Name
Maddalena OTTAVIANI
Site Name
Azienda Ospedaliero Universitaria Delle Marche
Department Name
Dipartimento di emergenza-urgenza ed accettazione (DEA)
Contact Person Name
Cinzia NITTI
Site Name
Azienda Socio Sanitaria Territoriale Di Cremona
Department Name
UO Cardiologia
Contact Person Name
Silvia FRATINNI
Site Name
Universita' Degli Studi Di Perugia
Department Name
Dipartimento di Medicina Interna e Cardiovascolare – Unità Ictus
Contact Person Name
Cecilia BECATTINI
Contact Person Email
cecilia.becattini@unipg.it
Site Name
Azienda Ulss 5 Polesana (additional site listed)
Department Name
Cardiology department
Contact Person Name
Claudio PICARIELLO

Slovenia

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
31-03-2025
Processing Time Days
304
Number Of Sites
1
Number Of Participants
10

Sites

Site Name
University Medical Center Ljubljana
Department Name
Department for Vascular Diseases
Contact Person Name
Matija KOZAK
Contact Person Email
matija.kozak@kclj.si

Sponsor

Primary sponsor

Full Name
Assistance Publique Hopitaux De Paris
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
France

Third parties

  • {"country":"France","full_name":"Aixial","duties_or_roles":"[\"1\",\"12\",\"5\",\"8\"]","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
ACTILYSE, poudre et solvant pour solution injectable et perfusion
Active Substance
ALTEPLASE
Modality
Peptide/protein/enzyme
Routes Of Administration
Intravenous use
Route
Intravenous
Authorisation Status
Market authorisation exists (marketingAuthNumber: 34009 558 530 1 5 in FR)
Maximum Dose
50 mg
Investigational Product Name
ACTILYSE 50mg placebo
Modality
Other
Authorisation Status
Not applicable / placebo

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