Clinical trial NCT02029456: Low Dose Prolonged Infusion of Tissue Type Plasminogen Activator Therapy in Massive Pulmonary Embolism
Official title: Low Dose Prolonged Infusion of Tissue Type Plasminogen Activator Therapy in Massive Pulmonary Embolism: AYKAN Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Pulmonary Embolism
Keywords: Massive Pulmonary embolism
thrombolytic therapy
high risk
elderly
Lead sponsor: Ahi Evren Chest and Cardiovascular Surgery Education and Research Hospital
Sponsor class: OTHER
First posted: 2014-01-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: All cause in hospital mortality
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 7 days
measure: Major complications
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 7 days.
measure: Development of pulmonary hypertension
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 7 days
measure: Right Ventricular dysfunction
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 7 days
measure: Restoration of hemodynamic status
timeFrame: 6 hours after the beginning of thrombolytic therapy
Secondary outcomes:
measure: Pulmonary hypertension
timeFrame: 6 month
measure: Right ventricular dysfunction
timeFrame: 6 months
Other outcomes:
Locations:
city: Trabzon
country: Turkey
facility: Department of Cardiology, Ahi Evren Chest and Cardiovascular Surgery Education and Research Hospital
Study officials:
affiliation: Department of Cardiology, Ahi Evren Chest and Cardiovascular Surgery Education and Research Hospital
name: Ahmet Ç AYKAN, MD
role: STUDY_CHAIR
References:
citation: Ozkan M, Cakal B, Karakoyun S, Gursoy OM, Cevik C, Kalcik M, Oguz AE, Gunduz S, Astarcioglu MA, Aykan AC, Bayram Z, Biteker M, Kaynak E, Kahveci G, Duran NE, Yildiz M. Thrombolytic therapy for the treatment of prosthetic heart valve thrombosis in pregnancy with low-dose, slow infusion of tissue-type plasminogen activator. Circulation. 2013 Jul 30;128(5):532-40. doi: 10.1161/CIRCULATIONAHA.113.001145. Epub 2013 Jun 28.
citation: Ozkan M, Gunduz S, Biteker M, Astarcioglu MA, Cevik C, Kaynak E, Yildiz M, Oguz E, Aykan AC, Erturk E, Karavelioglu Y, Gokdeniz T, Kaya H, Gursoy OM, Cakal B, Karakoyun S, Duran N, Ozdemir N. Comparison of different TEE-guided thrombolytic regimens for prosthetic valve thrombosis: the TROIA trial. JACC Cardiovasc Imaging. 2013 Feb;6(2):206-16. doi: 10.1016/j.jcmg.2012.10.016.