Pulmonary EmbolismPhase 3MONALYSENCT02604238
Efficacy and Safety of Half Dose Alteplase Added to Heparine, in Patients With Moderate Pulmonary Embolism
A Phase 3 study testing Alteplase in people with Pulmonary Embolism, run by Azienda U.S.L. 1 di Massa e Carrara.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Pulmonary Embolism
- What is being tested?
- Alteplase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Mar 2016to Mar 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- pulmonary embolism at intermediate risk as defined by the Guidelines ESC2014[ documented pulmonary CT angiography]
- pulmonary hypertension (systolic pulmonary pressure greater or equal to 40 mm Hg) [documented echocardiogram presence of thrombotic material in the right-sided]
- disfunction Ventricular right confirmed by echocardiogram or TC chest:
- dilation of the right sections (> 30 mm in parasternal or relationship right ventricle/left ventricle > 1)
- paradoxical movement of the interventricular septum
- TAPSE reduced (Tricuspid Annular Plane Systolic Excursion)
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- tricuspid regurgitation with gradient VD/AD> 30 mmHg, in the absence of right ventricular hypertrophy, McConnell sign (apical segment of the free wall of the right ventricle normalKinetic or hyperkinetic than a hypokinesia or akinesia of the remaining parts of the right ventricular wall),
- myocardial damage confirmed with:
- Troponin I or T positive
- higt value of the biomarkers of myocardial damage : BNP or NTproBNP
- informed consent
Who cannot join
- age <18 years and> 65 years
- HASBLED score ≥ 3 (23)
- intracranial tumors
- ischemic stroke within 2 months
- surgery neurological within 1 month and surgery within 10 days
- trauma within 15 days
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- hypotension to hospitalization (systemic blood pressure <90 mmHg)
- uncontrolled hypertension (SBP> 180mmHg and PAD> 110mmHg)
- clotting disorders
- thrombocytopenia (<100.000)
- platelet counts below 100 × 109 /L severe thrombocytopenia (platelet count <50.000 ptl / mm3)
- liver failure
- kidney failure
- gastrointestinal bleeding within 10 days
- pregnancy or childbirth within 30 days
- contraindications to the use of thrombolytics
- contraindications to the use of low molecular weight heparin (enoxaparin)
- anticoagulation therapy started more than 8 hours
- COPD
- endocarditis
- severe obesity
About this study
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
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
Read the detailed description
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).
- Conditions
- Pulmonary Embolism
- Being tested
- Alteplase
- Keywords
- Pulmonary Embolism at intermediate risk
- 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
Also called tPA-tissue Plasminigen Activator
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).
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | 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. Receives: Drug: Alteplase |
| Group B | No intervention | All patients are treated with low molecular weight heparin ( LMWH ) according to the Guidelines ESC2014 heparin. It not added any treatment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pulmonary hypertension reduction (systolic pulmonary pressure greater or equal to 30 mm Hg)
Pulmonary hypertension reduction documented on echocardiography
Measured: 24 hour
Secondary outcomes (3)
Incidence of recurrent pulmonary embolism fatal or non fatal
Incidence of recurrent pulmonary embolism fatal or non fatal
Measured: 7 days
Incidence of hemodynamic shock
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
Measured: 24 hour and 30 days
Incidence of hospital death from all causes
Incidence of hospital death from all causes
Measured: 30days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2015 (estimated)
- Study startMar 2016
- Primary completionMar 2016
- Study completionMar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary EmbolismStudies of the same condition, open and under way.
- 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
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda U.S.L. 1 di Massa e Carrara
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alberto Conti, MD, Principal investigator, Azienda USL1 di Massa e Carrara
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02604238
- Sponsor's protocol ID
- Azienda USL1 Massa e Carrara
- Acronym
- MONALYSE
- Status last verified
- Jun 2018
- First submitted
- 11 Nov 2015
- Last updated
- 8 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02604238
- Acronym / sponsor ID
- MONALYSE / Azienda USL1 Massa e Carrara
- Conditions
- Pulmonary Embolism
- Keywords
- Pulmonary Embolism at intermediate risk
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Azienda U.S.L. 1 di Massa e CarraraUniversity, hospital or other
- Study start
- Mar 2016 (actual)
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 13 Nov 2015 (estimated)
- 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.
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
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: AlteplaseAdministered 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. |
| Group B | No intervention | –All patients are treated with low molecular weight heparin ( LMWH ) according to the Guidelines ESC2014 heparin. It not added any treatment. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- pulmonary embolism at intermediate risk as defined by the Guidelines ESC2014[ documented pulmonary CT angiography]
- pulmonary hypertension (systolic pulmonary pressure greater or equal to 40 mm Hg) [documented echocardiogram presence of thrombotic material in the right-sided]
- disfunction Ventricular right confirmed by echocardiogram or TC chest:
- myocardial damage confirmed with:
- informed consent
Key exclusion criteria (21 listed)
- age <18 years and> 65 years
- HASBLED score ≥ 3 (23)
- intracranial tumors
- ischemic stroke within 2 months
- surgery neurological within 1 month and surgery within 10 days
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 |
|---|---|---|
| AlteplaseAlso: tPA-tissue Plasminigen ActivatorEnoxaparin (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). | Drug | Group A |
Primary outcome
Pulmonary hypertension reduction (systolic pulmonary pressure greater or equal to 30 mm Hg)
Time frame: 24 hour
Pulmonary hypertension reduction documented on echocardiography
3 secondary outcomes
Incidence of recurrent pulmonary embolism fatal or non fatal
Time frame: 7 days
Incidence of hemodynamic shock
Time frame: 24 hour and 30 days
Incidence of hospital death from all causes
Time frame: 30days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2024.
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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.
Alberto Conti, MD principal investigator
Azienda USL1 di Massa e Carrara
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Alteplase in people with Pulmonary Embolism, run by Azienda U.S.L. 1 di Massa e Carrara.
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 11 inclusion and 21 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: withdrawn, as of the sponsor's last update on 8 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Pulmonary hypertension reduction (systolic pulmonary pressure greater or equal to 30 mm Hg) (time frame: 24 hour). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Feb 2024.