Sildenafil To Prevent Clot (SToPClot)
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|ClinicalTrials.gov Identifier: NCT03199612|
Recruitment Status : Recruiting
First Posted : June 27, 2017
Last Update Posted : November 7, 2019
|Condition or disease||Intervention/treatment||Phase|
|Thrombosis Hemolysis||Drug: Sildenafil Drug: Placebo Oral Tablet||Early Phase 1|
Despite the remarkable improvements in survival with durable continuous flow (CF) pumps and the clear lifesaving effects of Impella and veno-arterial extracorporeal membrane oxygenation (VA ECMO), serious adverse hematological events such as bleeding and thrombosis create substantial morbidity and mortality and remain major barriers for further expansion of this technology. In particular, thrombosis is a devastating adverse event during CF pump support as it can lead to stroke, device stoppage, and hemodynamic collapse. Although the annual incidence of pump thrombosis has been reported to range from 8 to nearly 30%, the pathobiological mechanisms of thrombus formation during CF pump support with ongoing anticoagulation remain elusive. Our preliminary data associates hemolysis, which is inherent to such devices due to high shear stress, with subsequent formation of thrombosis and stroke, possibly through increasing platelet activation and aggregation. Our prelim data and drawing from a body of literature from diseases of intravascular hemolysis such as sickle cell anemia suggest that free hemoglobin released during hemolysis, which reduces NO levels, may be activating platelets. In retrospective analysis, we have noted a significant reduction in mean platelet volume (potential in-vivo marker of platelet activation), thrombosis and stroke with concurrent sildenafil administration. However, this mechanism and efficacy of NO signaling enhancers such as sildenafil remains to be proven during CF pump support.
Aim: To conduct a randomized placebo controlled study to test the hypothesis that platelet activation and aggregation, endothelial dysfunction and pro-thrombotic inflammation during ongoing low level hemolysis in outpatients on chronic CF pump support can be reduced by sildenafil.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||46 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Placebo controlled randomized trial with 1:1 enrollment in each study arm.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||The Role of Hemolysis in Promoting Thrombosis During Mechanical Circulatory Support With Continuous Flow Pumps (Aim 2)|
|Actual Study Start Date :||June 3, 2019|
|Estimated Primary Completion Date :||August 30, 2023|
|Estimated Study Completion Date :||August 30, 2023|
Active Comparator: Sildenafil
Baseline blood samples and study measurements will be acquired. Then 20 mg of the study drug will be administered. Then BP will be recorded every 30 minutes for two hours. If BP is stable (drop is < 5 mmHg after 2 hours and patient is asymptomatic), patient will proceed to take 20 mg of the study drug every 8 hours. The patient will return to clinic on day 8 and 20 mg of the study drug will be administered. After 2 hours blood samples and study measurements will be collected and the patient will resume 20 mg of the study for the next two doses. The patient will return for a third clinic visit on the next day and if BP is in the acceptable range, 40 mg of the study drug will be administered. If BP remains stable for 2 hours, then the patient will continue taking 40 mg every 8 hours. The patient will return to clinic on day 15 for a final study visit and will be given the last 40 mg dose of the study drug and after 2 hours blood samples and study measurements will be taken.
To conduct a randomized placebo controlled study to test the hypothesis that platelet activation and aggregation during ongoing low level hemolysis in outpatients on chronic CF pump support can be reduced by sildenafil.
Placebo Comparator: Placebo Oral Tablet
Negative control to understand the potential changes in platelet activation and aggregation in comparison to sildenafil.
Drug: Placebo Oral Tablet
Negative control to understand the potential changes in platelet activation adn aggregation in comparison to sildenafil.
Other Name: Sildenafil matching placebo
- Change in platelet activation and aggregation (aggregometry) [ Time Frame: Baseline, day 8 and day 15 ]During the study period platelet activation and aggregation will be measured from drawn blood samples. Platelet rich plasma will be isolated from these samples and platelet aggregometry will be used to measure platelet activation and aggregation.
- Changes in Endothelial Function as measured by the vascular reactivity index (VRI) [ Time Frame: Baseline, day 8 and day 15 ]During the study period endothelial function will be measured by the VRI as calculated by the Endothelix device, after a 5 minute blood pressure cuff occlusion of the brachial artery.
- Changes in Endothelial Function as measured by Endothelin 1 [ Time Frame: Baseline, day 8 and day 15 ]During the study period changes in endothelial function, will be measured by blood endothelin-1 (pg/mL) levels trough ELISA
- Change in pro-thrombotic inflammatory markers as measured by hs CRP [ Time Frame: Baseline, day 8 and day 15 ]During the study period pro-thrombotic inflammatory markers, including hs CRP (mg/L) in serum will be measured by ELISA.
- Change in pro-thrombotic inflammatory markers as measured by fibrinogen [ Time Frame: Baseline, day 8 and day 15 ]During the study period pro-thrombotic inflammatory markers including fibrinogen (mg/dL) will be measured by ELISA.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03199612
|Contact: Thiru Chinnadurai, MDfirstname.lastname@example.org|
|Contact: Omar Saeed, MDemail@example.com|
|United States, New York|
|Montefiore Medical Center||Recruiting|
|Bronx, New York, United States, 10467|
|Contact: Omar Saeed, MD 718-920-2626 firstname.lastname@example.org|
|Principal Investigator:||Omar Saeed, MD||Montefiore Medical Center|