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Low Dose Prolonged Infusion of Tissue Type Plasminogen Activator Therapy in Massive Pulmonary Embolism

Phase 4
Conditions
Pulmonary Embolism
Interventions
Drug: 25 mg Actilyse ( Boehringer Ingelheim, Germany) infusion in 6 hours
Registration Number
NCT02029456
Lead Sponsor
Ahi Evren Chest and Cardiovascular Surgery Education and Research Hospital
Brief Summary

The aim of the present study was to assess the effects of low-dose (25mg) prolonged administration (in 6 hours) of tissue type plasminogen activator (tPA) on in-hospital mortality and outcomes in patients with massive PE.

Detailed Description

Pulmonary embolism (PE) is life threatening disease requiring early diagnosis and treatment. Thrombolytic therapy (TT) is required in patients with massive PE. PE has a high mortality but the in-hospital all-cause case mortality rates were lower in unstable patients who received TT than those who did not. However, it was reported that minority (nearly 30%) of unstable patients received thrombolytic therapy. The reason that majority of unstable patients failed to receive thrombolytic therapy is unclear. The higher rates of complications including the life threatening bleeding may be a reason of reluctance in the use of TT.

The lungs are the only organ receiving the entire cardiac output. Therefore, they are the point of convergence for the entire molecules of the thrombolytic agent, independent from the route of administration. So that lower doses of the TT might be effective in PE, with the additional benefits of enhancing its safety profile. The percutaneous endovenous intervention for deep venous thrombosis has suggested an exquisitely favorable pulmonary response to low-dose thrombolysis. The aim of the present study was to assess the effects of low-dose (25mg) prolonged administration (in 6 hours) of tissue type plasminogen activator (tPA) on in-hospital mortality and outcomes in patients with massive PE.

The primary end points consisted of in hospital all cause mortality, major complications, pulmonary hypertension and right ventricular dysfunction. Secondary points are all cause mortality, pulmonary hypertension and right ventricular dysfunction at 6 month.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
30
Inclusion Criteria

Patients with massive PE aged 18 years or older with confirmed PE and able to give informed consent will be included in the study. PE is defined according to current guidelines as adult patients presenting with signs and symptoms suggestive of PE plus imaging documentation on computed tomography angiography. Massive PE was defined as acute PE with sustained hypotension (systolic blood pressure<90 mm Hg for at least 15 minutes or requiring inotropic support, not due to a cause other than PE, such as arrhythmia, hypovolemia, sepsis, or left ventricular [LV] dysfunction), pulselessness, or persistent profound bradycardia (heart rate<40 bpm with signs or symptoms of shock).

Exclusion Criteria

Patients with prior intracranial hemorrhage, known structural intracranial cerebrovascular disease (eg, arteriovenous malformation), known malignant intracranial neoplasm, ischemic stroke within 3 months, suspected aortic dissection, active bleeding or bleeding diathesis, recent surgery encroaching on the spinal canal or brain, and recent significant closed-head or facial trauma with radiographic evidence of bony fracture or brain injury were excluded from the study.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Low dose prolonged infusion arm25 mg Actilyse ( Boehringer Ingelheim, Germany) infusion in 6 hoursLow dose prolonged infusion of tPA arm (25mg Actilyse in 6 hours)
Primary Outcome Measures
NameTimeMethod
All cause in hospital mortalityparticipants will be followed for the duration of hospital stay, an expected average of 7 days

Death occured during hospitalization period.

Major complicationsparticipants will be followed for the duration of hospital stay, an expected average of 7 days.

Major bleeding, intracranial bleeding, resuscitated cardiac arrest, thromboembolism and stroke are described as major complications.

Development of pulmonary hypertensionparticipants will be followed for the duration of hospital stay, an expected average of 7 days

Pulmonary artery systolic pressure \>40mmHg measured by transthoracic echocardiography prior to discharge was described as pulmonary hypertension.

Right Ventricular dysfunctionparticipants will be followed for the duration of hospital stay, an expected average of 7 days

Right ventricular dysfunction detected by transthoracic echocardiography:

1. Decreased right ventricular diameter (at least 25% decrease of Right ventricle/Left ventricle diameter)

2. Tricuspid annular plane systolic excursion\>16mm)

3. s'\> 10.0 cm/s

4. Tissue Doppler derived right ventricle myocardial performance index\>0.55

Restoration of hemodynamic status6 hours after the beginning of thrombolytic therapy

Systolic blood pressure \>100mmHG

Secondary Outcome Measures
NameTimeMethod
Pulmonary hypertension6 month

Pulmonary artery systolic pressure \>40mmHg

Right ventricular dysfunction6 months

1. Tricuspid annular plane systolic excursion \>16mm

2. s'\> 10.0 cm/s

3. Tissue Doppler derived right ventricle myocardial performance index\>0.55

4. Right ventricle/Left ventricle diameter \<1

Trial Locations

Locations (1)

Department of Cardiology, Ahi Evren Chest and Cardiovascular Surgery Education and Research Hospital

đŸ‡¹đŸ‡·

Trabzon, Turkey

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