Sidlenafil in Combination With Oral Anticoagulants in Patients With Intermediate-high Risk of Pulmonary Embolism

Study Overview
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Brief Summary
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Pilot randomized study of the sidlenafil efficacy in combination with oral anticoagulants in the treatment of patients with intermediate-high risk of pulmonary embolism

Official Title
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Pilot Randomized Study of the Sidlenafil Efficacy in Combination With Oral Anticoagulants in the Treatment of Patients With Intermediate-high Risk of Pulmonary Embolism

Conditions
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Pulmonary Embolism, Intermediate-high Risk, Combination of Oral Anticoagulation Therapy and Sildenafil

Intervention / Treatment
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* Drug: Sildenafil/apixaban
* Drug: apixaban


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: pulmonary embolism confirmed by CT scan with contrast, with localization of thrombusa in at least one main or proximal lobar pulmonary artery. Right-left ventricular ratio (RV / LV) ≥1 derived from the apical four-chamber view Who gave written informed consent to participate in research Exclusion Criteria: Age <18 or >80 years Symptoms of pulmonary embolism> 14 days Inadequate echocardiographic image quality in the apical four-chamber projection, which limits the measurement of RV / LV ratio A significant risk of bleeding The administration of thrombolytic drugs within the previous 4 days Active bleeding Known coagulopathy Thrombocytopenia <100,10^9 / l Previous use of vitamin K antagonists with an INR> 2.5 at admission History of any intracranial or spinal surgery or trauma or intracranial / spinal bleeding Intracranial neoplasm Arteriovenous malformations or aneurysms GIH <3 months Cataract Surgery Obstetrical manipulation Cardiopulmonary resuscitation needed. Other invasive procedures <10 days Allergy, hypersensitivity, thrombocytopenia to heparin or tissue plasminogen activator Allergy to iodine contrast A well-known right-left cardiac shunt, for example, a large patent foramen ovale, or atrial septal defect; large (> 10 mm), or a blood clot in right atrium/right ventricle Systolic blood pressure <90 mm Hg for at least 15 minutes, or fall of systolic blood pressure is not less than 40 mm Hg for at least 15 min., with evidence of organ hypoperfusion (cold extremities or low diuresis <30 mL / h, or confusion), or the need for administration of catecholamines to maintain adequate perfusion of organs and systolic blood pressure> 90 mm Hg Severe hypertension (systolic> 180 mm Hg or diastolic> 105 mm Hg.). Pregnancy, lactation, delivery<30 days Participation in any other study (drug or device) Life expectancy <90 days Refusal to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: double drug therapy<br> | Drug: Sildenafil/apixaban<br>* After arrival to the emergency department, a series of surveys to determine the risk of death from pulmonary embolism are carried out. Then angiography, tensiometry of SBCC, catheter thrombus fragmentation are scheduled. Then puncture of the right jugular vein is performed. PigTail catheter is inserted via guidewire into the pulmonary artery . Angiography of the pulmonary arteries is performed. Miller index is calculated. Catheter thrombus fragmentation is performed by a PigTail catheter. RV, RA pressures are measured. In the ICU heparin is prescribed (of 1000 units per hour) under the control of PTT (50-75s). The next day patients are randomizaed to assign them into 2 groups. Dual drug therapy is going to be administered to this group (experimental): sildenafil 30mg 3p \ g + 10 mg apixaban 2p \ d for 14 days. On the 7th day MSCT angiography of the pulmonary aretry with contrast and echocardiogram are performed. On the 14th day the controlechocardiogram is performed .<br>|
| Active Comparator: mono drug therapy<br> | Drug: apixaban<br>* After arrival to the emergency department, a series of surveys to determine the risk of death from pulmonary embolism are carried out. Then angiography, tensiometry of SBCC, catheter thrombus fragmentation are scheduled. Then puncture of the right jugular vein is performed. PigTail catheter is inserted via guidewire into the pulmonary artery . Angiography of the pulmonary arteries is performed. Miller index is calculated. Catheter thrombus fragmentation is performed by a PigTail catheter. RV, RA pressures are measured. In the ICU heparin is prescribed (of 1000 units per hour) under the control of PTT (50-75s). The next day patients are randomizaed to assign them into 2 groups.Mono drug therapy is going to be administered to this group (active comparator): apixaban 10 mg 2p \ d for 14 days. On the 7th day MSCT angiography of the pulmonary aretry with contrast and echocardiogram are performed. On the 14th day the controlechocardiogram is performed .<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MSCT RV \ LV Index | on the 7th day of treatment RV \ LV Index (calculated according to MSCT angiography of the pulmonary arteries) | 7th day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Echocardiogram RV \ LV Index | Echocardiogram (an index of RV \ LV) on 7th day | 7th day | 
| Echocardiogram RV \ LV Index | Echocardiogram (an index of RV \ LV) on 14th day | 14th day | 
| Echocardiogram RV \ LV Index | Echocardiogram (an index of RV \ LV) on one month | one month | 
| Echocardiogram pressure in the pulmonary artery | the average pressure in the pulmonary artery according to echocardiography | one month | 
| hemodynamic instability | in the hospital and within a month follow-up | one month | 
| death | in the hospital and within a month follow-up | one month | 
| bleeding | clinically significant bleeding on a scale HAS-BLED | one month | 
| recurrent venous thrombosis | recurrent venous thrombosis | one month | 
| recurrent pulmonary embolism | recurrent pulmonary embolism. | one month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Embolism, sildenafil, oral anticoagulation therapy