Sildenafil To Prevent Clot
Mots clés
Abstrait
La description
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.
Rendez-vous
| Dernière vérification: | 10/31/2019 |
| Première soumission: | 06/21/2017 |
| Inscription estimée soumise: | 06/22/2017 |
| Première publication: | 06/26/2017 |
| Dernière mise à jour soumise: | 11/05/2019 |
| Dernière mise à jour publiée: | 11/06/2019 |
| Date de début réelle de l'étude: | 06/02/2019 |
| Date d'achèvement primaire estimée: | 08/29/2023 |
| Date estimée d'achèvement de l'étude: | 08/29/2023 |
Condition ou maladie
Intervention / traitement
Drug: Sildenafil
Drug: Placebo Oral Tablet
Phase
Groupes d'armes
| Bras | Intervention / traitement |
|---|---|
| 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. | Drug: Sildenafil 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. |
Critère d'éligibilité
| Âges éligibles aux études | 18 Years À 18 Years |
| Sexes éligibles à l'étude | All |
| Accepte les bénévoles en santé | Oui |
| Critères | Inclusion: -Adult outpatients (≥18 years old) with ongoing durable CF pump support. Exclusion: - Taking sildenafil or nitrates for clinical indications - Ongoing infection - Unwilling or unable to give written, informed consent |
Résultat
Mesures des résultats primaires
1. Change in platelet activation and aggregation (aggregometry) [Baseline, day 8 and day 15]
Mesures des résultats secondaires
1. Changes in Endothelial Function as measured by the vascular reactivity index (VRI) [Baseline, day 8 and day 15]
2. Changes in Endothelial Function as measured by Endothelin 1 [Baseline, day 8 and day 15]
3. Change in pro-thrombotic inflammatory markers as measured by hs CRP [Baseline, day 8 and day 15]
4. Change in pro-thrombotic inflammatory markers as measured by fibrinogen [Baseline, day 8 and day 15]
