Pulmonary Embolism International Thrombolysis Trial: A reduced dose of thrombolytic treatment for patients with intermediate high-risk acute pulmonary embolism: a randomized controlled trial.

Phase 3

Not yet recruiting

Conditions: longembolie
blockage in one of the pulmonary arteries in your lungs

Registration Number: NL-OMON56449

Lead Sponsor: Assistance Publique - Hôpitaux de Paris, Clinical Research and Innovation Direction (DRCI)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 75

Inclusion Criteria

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) 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;
* *cute 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 (SBP) <= 110 mm Hg over at least 15 min upon enrolment, (b) 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; (c) respiratory
rate > 20/min or SpO2 < 90% (or partial arterial oxygen pressure < 60 mm Hg) at
rest while breathing room air, (d) 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;
* 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);
* 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 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 latest;
* Signed informed consent form;
* [France] Patient insured under a social security system

Exclusion Criteria

* Hemodynamic instability, defined by at least one of the following criteria
- cardiac arrest;
- obstructive shock, defined as: (i) SBP < 90 mm Hg, or vasopressors required
to achieve a SBP >= 90 mmHg despite an adequate filling status; and (ii)
end-organ hypoperfusion (altered mental status; cold, clammy skin;
oliguria/anuria; increased serum lactate);
- isolated persistent hypotension (SBP < 90 mm Hg, or a systolic pressure drop
>= 40 mm Hg for > 15 min), if not caused by new-onset arrhythmia, hypovolemia,
or sepsis
* 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 the previous 3 weeks
* Platelet count < 100 x 109/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 anti-platelet 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
* [Italy and the Netherlands] Participation in another interventional clinical
study within 30 days from the inclusion
* [All countries except Italy and the Netherlands] 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 in the investigator*s opinion 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