Platelet Reactivity and Treatment With Prostacyclin Analogues in Pulmonary Arterial Hypertension

Pulmonary Hypertension Clinical Trial

— PAPAYA  

Official title:

Platelet Reactivity and Treatment With Prostacyclin Analogues in Pulmonary Arterial Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04578223
• Other study ID #: KB/138/217
• Status: Completed
• Start date: July 5, 2017
• Est. completion date: September 23, 2020

Study information

• Verified date: September 2020
• Source: Medical University of Warsaw
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: September 23, 2020
• Est. primary completion date: November 30, 2019
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of Warsaw	European Health Centre Otwock

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Platelet reactivity	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
Secondary	Concentration of extracellular vesicles from platelets, leukocytes and endothelial cells	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
Secondary	Platelet-rich thrombus formation parameters	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