PAPAYA: Platelet Reactivity and Treatment With Prostacyclin Analogues in Pulmonary Arterial Hypertension

• Sponsor: Medical University of Warsaw (Other)
• Overall Status: Completed
• CT.gov ID: NCT04578223
• Collaborator: European Health Centre Otwock (Other)
• Enrollment: 80
• Location: 1
• Actual Duration (Months): 38.6
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Hypertension

Study Design

• Study Type: Observational
• Actual Enrollment: 80 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Platelet Reactivity and Treatment With Prostacyclin Analogues in Pulmonary Arterial Hypertension
• Actual Study Start Date: Jul 5, 2017
• Actual Primary Completion Date: Nov 30, 2019
• Actual Study Completion Date: Sep 23, 2020

Arms and Interventions

Arm	Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

1. Platelet reactivity [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

Secondary Outcome Measures

1. Concentration of extracellular vesicles from platelets, leukocytes and endothelial cells [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

2. Platelet-rich thrombus formation parameters [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Pulmonary Circulation, Thromboembolic Diseases and Cardiology, Centre of Postgraduate Education Medical, European Health Centre Otwock	Warsaw		Poland

Sponsors and Collaborators

• Medical University of Warsaw
• European Health Centre Otwock

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Medical University of Warsaw
• ClinicalTrials.gov Identifier: NCT04578223
• Other Study ID Numbers: KB/138/217
• First Posted: Oct 8, 2020
• Last Update Posted: Oct 9, 2020
• Last Verified: Sep 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Medical University of Warsaw: prostacyclin analogues; pulmonary arterial hypertension; platelet reactivity; extracellular vesicles; thrombus formation
• Additional relevant MeSH terms: Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Hypertension

Study Results

No Results Posted as of Oct 9, 2020