Reduced-Dose Versus Full-Dose Alteplase for High-Risk Pulmonary Embolism
ConditionPulmonary Embolism Acute
Trial statusNot yet recruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorSahlgrenska University Hospital
About this trial
High-risk pulmonary embolism is a life-threatening condition requiring immediate reperfusion therapy. Full-dose systemic thrombolysis is recommended as first-line treatment, but its use is limited by the risk of major bleeding, including intracranial hemorrhage. Reduced-dose systemic thrombolysis may reduce bleeding while maintaining clinical efficacy, but this strategy has not been adequately evaluated in patients with high-risk pulmonary embolism.
REDSTEM is an international, multicenter, randomized, adaptive, open-label, blinded-endpoint phase 4 trial comparing reduced-dose alteplase with standard full-dose alteplase in adults with acute high-risk pulmonary embolism. The trial will assess whether reduced-dose alteplase preserves early clinical efficacy while reducing severe clinically significant bleeding. Participants will be followed for up to 12 months.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Participant aged 18 years or older.
Acute pulmonary embolism verified by computed tomography pulmonary angiography or pulmonary angiography. In hemodynamically unstable participants unable to undergo immediate imaging, presumed pulmonary embolism may be diagnosed based on bedside echocardiographic findings consistent with acute right ventricular pressure overload and high clinical suspicion of pulmonary embolism, provided that alternative causes of hemodynamic instability have been reasonably excluded. In such cases, the treating clinician must have independently decided to initiate thrombolytic therapy irrespective of study participation, and confirmatory imaging demonstrating pulmonary embolism must be performed as soon as clinically feasible.
Cardiac arrest with return of spontaneous circulation;
Obstructive shock, defined as systolic blood pressure <90 mmHg or use of vasopressors to maintain systolic blood pressure ≥90 mmHg despite adequate filling status, together with end-organ hypoperfusion such as elevated serum lactate >2 mmol/L, altered mental status, or cold clammy skin;
Disqualifiers
Catastrophic pulmonary embolism, defined as ongoing cardiac arrest and/or need for extracorporeal cardiopulmonary resuscitation and/or immediate VA-ECMO as judged by the treating physicians.
Known hypersensitivity to alteplase or any of its excipients.
History of hemorrhagic stroke;
Ischemic stroke within the previous 6 months;
Trial design
Design model
Parallel
Treatments tested in this trial
Reduced-dose alteplase
DrugAlteplase 0.6 mg/kg body weight, maximum 50 mg, administered as an intravenous infusion over 15 minutes
Full-dose alteplase
DrugAlteplase 1.5 mg/kg body weight, maximum 100 mg, administered as a 10 mg intravenous bolus over 1 to 2 minutes followed by 90 mg as an intravenous infusion over 2 hours.
Treatment groups
400 Participants
are divided into 2 treatment groupsGroup A: Reduced-Dose AlteplaseExperimental treatment 1 intervention
Group B: Full-Dose AlteplaseActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Incidence of composite efficacy endpoint
Incidence of a composite endpoint comprising all-cause mortality within 7 days, cardiopulmonary resuscitation and/or veno-arterial extracorporeal membrane oxygenation within 7 days, recurrent pulmonary embolism within 7 days, clinical deterioration within 24 hours, and lack of clinical improvement at 6 hours.
Time frame
Within 7 days after randomization2
Key secondary endpoint - Incidence of severe clinically significant bleeding
Incidence of severe clinically significant bleeding, defined as major bleeding according to International Society on Thrombosis and Haemostasis criteria or bleeding requiring urgent medical intervention.
Time frame
Within 7 days after randomizationSecondary outcomes
1
All-cause mortality
Incidence of death from any cause.
Time frame
At 7 days and 30 days after randomization2
Pulmonary embolism-related mortality
Incidence of pulmonary embolism-related death.
Time frame
At 7 days and 30 days after randomization3
Cardiopulmonary resuscitation and/or VA-ECMO
Incidence of cardiopulmonary resuscitation and/or veno-arterial extracorporeal membrane oxygenation.
Time frame
Within 7 days after randomization4
Incidence of clinical deterioration
Incidence of life-threatening hemodynamic or respiratory decline requiring cardiopulmonary resuscitation, endotracheal intubation, or VA-ECMO, or an increase in SCAI SHOCK stage after investigational medicinal product administration.
Time frame
Within 24 hours after randomizationOther outcomes
1
All-cause mortality at 12 months
Incidence of death from any cause.
Time frame
At 12 months after randomization2
At 12 months after randomization
Incidence of objectively confirmed recurrent pulmonary embolism.
Time frame
At 12 months after randomization3
Persistent dyspnea assessed using the modified Medical Research Council scale
Persistent dyspnea assessed using the modified Medical Research Council scale.
Time frame
At 3 months and 12 months after randomization4
Functional status assessed using the Post-VTE Functional Status Scale
Functional status assessed using the post-VTE functional status (PVFS) scale. Scores range from 0 to 4, where 0 indicates no functional limitations and 4 indicates severe functional limitations. Higher scores indicate worse functional status. Death before the scheduled assessment is recorded as grade D.
Time frame
At 3 months and 12 months after randomizationSponsors and contacts
Click on the lead sponsor to view all of their trials.
Sahlgrenska University Hospital
Lead sponsor
Göteborg University
Collaborator
Leiden University Medical Center
Collaborator
Assistance Publique - Hôpitaux de Paris
Collaborator
Rigshospitalet, Denmark
Collaborator
University Hospital, Akershus
Collaborator
University of Zurich
Collaborator
Source ClinicalTrials.gov
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