Efficacy and Safety of Half Dose Alteplase Added to Heparine, in Patients With Moderate Pulmonary Embolism (MONALYSE)
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|ClinicalTrials.gov Identifier: NCT02604238|
Recruitment Status : Not yet recruiting
First Posted : November 13, 2015
Last Update Posted : November 16, 2015
The primary aim of this study is to evaluate whether mid dose (safe dose) of Alteplase in addition to standard treatment with heparin (LMWH) in patients with pulmonary embolism (PE) at intermediate risk, it is effective to reduce:
- right ventricular dysfunction
- pulmonary hypertension 24 hours and 7 days after the treatment
- PE recurrence to 7days and 30 days after the treatment without increasing the incidence of bleeding intra-extracranial
|Condition or disease||Intervention/treatment||Phase|
|Pulmonary Embolism||Drug: Alteplase||Phase 3|
The guidelines of the European Society of Cardiology (ESC2014) confirm the indication for pharmacological revascularization with thrombolysis only to cases of pulmonary embolism at high risk and thus hemodynamically unstable (class of recommendation I, level of evidence B), reserving the surgical or interventional procedures to cases where thrombolysis has failed or is contraindicated, while it remains controversial the role of thrombolysis in patients with pulmonary embolism at intermediate risk; the current state, in EP intermediate risk, the standard treatment involves the administration of low molecular weight heparin (LMWH), or fondaparinux (for 5-10 days followed by anticoagulation therapy with vitamin K antagonists) or alternatively the new anticoagulants oral (NAO). Although the results of the study PEITHO, recently published, confirm the indication for thrombolytic therapy for primary reperfusion in patients with embolism pulmonary high risk and provide element of reflection about the incidence of intracranial hemorrhage major, recent studies suggest that the thrombolysis with tPA to reduced dose (about half the dose that used in standard thrombolysis) in addition to anticoagulants (low molecular weight heparin) may reduce pulmonary hypertension (systolic artery pulmonary pressure> 40 mmHg) and the incidence of recurrent PE. In this protocol, based on the study MOPETT and pharmacokinetic data available, it is used a "safe dose" (safe dose reduced) of alteplase which provides a intravenous (iv) bolus loading dose of 10 mg in 1 min, followed by intravenous infusion 40 mg within two hours (for patients weighing <50 kg loading dose iv bolus of 0.5 mg in 1 min, followed by iv infusion of 40 mg within two hours).
After treatment with alteplase, the heparin therapy will be resumed when aPTT values are less than twice the upper limit of normal; the infusion will be adjusted to maintain aPTT between 50-70 seconds (1.5 to 2.5 times the reference value), and for safety reasons are excluded patients> 65 -70 years (increased risk of bleeding complications related age and comorbidities).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||130 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Efficacy and Safety of Thrombolytic Therapy With Half Dose Alteplase, Added to Standard Anticoagulation Therapy With Heparine, in Patients With Moderate Pulmonary Embolism: a Prospective, Randomized, Open Label,Controlled Trial|
|Study Start Date :||March 2016|
|Estimated Primary Completion Date :||March 2020|
|Estimated Study Completion Date :||March 2021|
Experimental: Group A
Administered a "safe dose" of Alteplase. All patients are treated with low molecular weight heparin ( LMWH ) according to the Guidelines ESC2014 heparin in addition it is administered a "safe dose" of Alteplase.
Enoxaparin (1mg) 100UI aXa/kg/sc [LMWH], 15 -30 minutes prior to administration of intravenous (iv) bolus loading dose of 10 mg in 1 min, followed by iv infusion of 40 mg within two hours (for patients weighing <50 kg, a loading dose of bolus of 0.5 mg in 1 min, followed by iv infusion of 40 mg in two hours); the infusion will be adjusted to maintain the value of aPTT between 50-70 seconds (1.5 to 2.5 times the reference value).
Other Name: tPA-tissue Plasminigen Activator
No Intervention: Group B
All patients are treated with low molecular weight heparin ( LMWH ) according to the Guidelines ESC2014 heparin. It not added any treatment.
- Pulmonary hypertension reduction (systolic pulmonary pressure greater or equal to 30 mm Hg) [ Time Frame: 24 hour ]Pulmonary hypertension reduction documented on echocardiography
- Incidence of recurrent pulmonary embolism fatal or non fatal [ Time Frame: 7 days ]Incidence of recurrent pulmonary embolism fatal or non fatal
- Incidence of hemodynamic shock [ Time Frame: 24 hour and 30 days ]Incidence of hemodynamic shock [defined as: need for cardiopulmonary resuscitation, or SBP <90 mmHg for a period ≥15 min or reduction SBP ≥40 mm Hg for SBP ≥15 min, with evidence of systemic hypoperfusion (cold extremities, diuresis <30 mL / h, mental confusion), or need for infusion of amines to maintain adequate organ perfusion and SBP> 90 mm Hg
- Incidence of hospital death from all causes [ Time Frame: 30days ]Incidence of hospital death from all causes
- Bleeding extracranial minor and major [ Time Frame: 24 hour and 30 days ]Bleeding extracranial minor and major
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02604238
|Contact: Alberto Conti, MDemail@example.com|
|Contact: Lorella Magnani, PharmDfirstname.lastname@example.org|
|Principal Investigator:||Alberto Conti, MD||Azienda USL1 di Massa e Carrara|