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

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

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

Study Overview

• Status: Unknown
• Conditions: Pulmonary Embolism; Intermediate-high Risk; Combination of Oral Anticoagulation Therapy and Sildenafil
• Intervention / Treatment: Drug: Sildenafil/apixaban; Drug: apixaban

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Novosibirsk, Russian Federation, 630055
    • Recruiting
    • Federal State Institution Academician E.N.Meshalkin Novosibirsk State Research Institute Of Circulation Pathology Rusmedtechnology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: double drug therapy	Drug: Sildenafil/apixaban; 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 .
ACTIVE_COMPARATOR: mono drug therapy	Drug: apixaban; 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 .

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Meshalkin Research Institute of Pathology of Circulation

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (ANTICIPATED): October 1, 2020
• Study Completion (ANTICIPATED): October 1, 2020

Study Registration Dates

• First Submitted: October 20, 2016
• First Submitted That Met QC Criteria: October 25, 2016
• First Posted (ESTIMATE): October 27, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): November 1, 2016
• Last Update Submitted That Met QC Criteria: October 29, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: sildenafil; Pulmonary Embolism; oral anticoagulation therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Pulmonary Embolism; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Apixaban; Sildenafil Citrate
• Other Study ID Numbers: NRICP-45734