Platelet Reactivity and Treatment With Prostacyclin Analogues in Pulmonary Arterial Hypertension (PAPAYA)
Background: Prostacyclin analogues (epoprostenol, treprostinil and iloprost) induce vasodilation in advanced pulmonary arterial hypertension (PAH) but also inhibit platelets, increasing patients' bleeding risk. The antiplatelet effects of different prostacyclin analogues have never been compared head-to-head. The goal of the PAPAYA (Platelet Reactivity and Treatment With Prostacyclin Analogues in Pulmonary Arterial Hypertension) trial is(i) to compare platelet function (platelet reactivity, extracellular vesicles concentration and thrombus formation) in patients with PAH treated with prostacyclin analogues on top of endothelin receptor antagonists (ERA) and/or phosphodiesterase type 5 inhibitors (PDE5i) and patients treated only with ERA and PDE5i, and (ii) to compare the antiplatelet effect of different prostacyclin analogues.
Venous blood will be collected from patients treated with prostacyclin analogues (study group; n=40) and patients treated with ERA or PDE5i (control group; n=40). Platelet reactivity will be analysed in whole blood by impedance aggregometry using arachidonic acid, adenosine diphosphate and thrombin receptor-activating peptide as agonists. Concentrations of extracellular vesicles from all platelets (CD61+), activated platelets (CD62P+), leukocytes (CD45+) and endothelial cells (CD146+) will be analysed in platelet-depleted plasma using flow cytometry (A-60 Micro). Platelet-rich thrombus formation will be measured using whole blood perfusion system. The study will determine the antiplatelet effect of prostacyclin analogues and compare different prostacyclin analogues head-to-head to identify the best drugs to use in case of thrombosis or bleeding.
Aperçu de l'étude
Statut
Les conditions
Type d'étude
Inscription (Réel)
Contacts et emplacements
Lieux d'étude
-
-
-
Warsaw, Pologne
- Department of Pulmonary Circulation, Thromboembolic Diseases and Cardiology, Centre of Postgraduate Education Medical, European Health Centre Otwock
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
Méthode d'échantillonnage
Population étudiée
La description
Inclusion Criteria:
- Informed consent to participate in the study
- Pulmonary arterial hypertension confirmed with right heart catheterization
- Treatment with prostacyclin analogues (epoprostenol, treprostinil, iloprost) - study group
- Treatment with endothelin receptor antagonists and phosphodiesterase type 5 inhibitors - control group
Exclusion Criteria:
- Known coagulopathy
- Active pathological bleeding
- Known history of bleeding disorder
- Severe thrombocytopenia (platelet count < 50,000/μL )
- Need for antiplatelet therapy with acetylsalicylic acid or P2Y12 antagonists
- Severe chronic renal failure (estimated glomerular filtration rate < 30 mL/min)
- Severe liver insufficiency (Child-Pugh class C)
- Known pregnancy, breast-feeding, or intention to become pregnant during the study period
- Study drug intolerance
- Participation in any previous study with prostacyclin analogues
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
|---|
|
Study group
Patients with pulmonary arterial hypertension treated with prostacyclin analogues on top of ERA or PDE-5i.
|
|
Control group
Patients with pulmonary arterial hypertension treated with ERA or PDE-5i only.
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Platelet reactivity
Délai: July 5, 2017 - November 30, 2019
|
Difference in platelet reactivity between patients treated with prostacyclin analogues and treated with ERA and/ or PDE5-i, assessed using impedance aggregometry
|
July 5, 2017 - November 30, 2019
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Concentration of extracellular vesicles from platelets, leukocytes and endothelial cells
Délai: July 5, 2017 - November 30, 2019
|
Differences in concentration of extracellular vesicles from platelets, leukocytes and endothelial cells between patients treated with prostacyclin analogues and treated with ERA and/ or PDE5i, assessed using flow cytometry
|
July 5, 2017 - November 30, 2019
|
|
Platelet-rich thrombus formation parameters
Délai: July 5, 2017 - November 30, 2019
|
Differences in platelet-rich thrombus formation parameters between patients treated with prostacyclin analogues and treated with ERA and/ or PDE5i, assessed using whole-blood flow-chamber perfusion system
|
July 5, 2017 - November 30, 2019
|
Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- KB/138/217
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Étudie un produit d'appareil réglementé par la FDA américaine
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .