Bosentan in Myocardium Metabolism and Perfusion Measured by 18F-FDG and 82Rb PET/CT on PAH and CTEPH

Terminated

• Conditions: Endothelial Dysfunction; Myocardial Dysfunction

• Registration Number: NCT02970851
• Lead Sponsor: University of Lausanne Hospitals

Brief Summary

The purpose of this study is to assess the effect of bosentan on the myocardial metabolism and the dependent endothelial coronary vasomotoricity in patients presenting a PAH.

Hypothesis : Bosentan may improve right ventricular function by decreasing myocardial stress and glucose metabolism. Patients may benefit from images with 18F-FDG PET / CT and 82Rb PET / CT for an earlier assessment and optimal management of PAH.

Detailed Description

Patients refered to the hospital for a right heart catheterization for a PAH suspected at the echocardiography will be presented with the protocol.If inclusion/exclusion criteria are fulfilled all the procedures will be planned. At the screening visit the patient will have a right heart catheterization and an echocardiography. After a maximum of 4 weeks each patient will have 18F-FDG and 82Rb PET/CTs before start of treatment with Bosentan. These PET/CTs together with an echocardiography will be repeated at 6 and 12 weeks after start of treatment with bosentan.

Finally a right heart catheterization will be planned at 12 weeks after start of treatment with bosentan as a routine procedure.

Study Timeline

• Study Start: 2013-04
• Study First Submitted: 2016-06-19
• Study First Submitted QC: 2016-11-17
• Study First Posted: 2016-11-22
• Primary Completion: 2018-12-31
• Study Completion: 2018-12-31
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-18
• Last Update Posted: 2020-03-23

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

• Patients with chronic PAH (PH group 1 Dana Point / stages 2 à 4 according to NYHA classification, defined by a mean arterial pulmonary pressure >25 millimeter of mercury (mmHg) at rest, an occlusion arterial pulmonary pressure <15 millimeter of mercury (mmHg) and vascular pulmonary resistance >240 dyn.s.cm-5 for which a treatment with bosentan is indicated Or Patients with CTEPH not candidate for a pulmonary endarterectomy or patient with residual CTEPH after pulmonary endarterectomy (PH group 4 Dana Point / stages 2 to 4 according to NYHA classification) and for which a treatment with bosentan is indicated
• Indication to perform a right heart catheterization in the context of PAH suspected during cardiac ultrasound
• Age from 18 to 80 years old, male and female
• Karnofsky index ≥80%
• Informed consent signed

Exclusion Criteria

• Patients with PAH stages 2,3 or 5 of Dana Point
• Patients with a contra-indication to adenosine including severe uncontrolled asthma, severe uncontrolled chronic obstructive pulmonary disease, 2nd or 3rd degree atrioventricular block without pacemaker,
• Patients with a contraindication to Bosentan, i.e :hypersensibility to the product, hepatic failure Child Pugh B or C, aminotransferases >3 times normal value (N),association with cyclosporine A or glibenclamide
• Pregnancy, female of child-bearing potential not using any acceptable contraceptive method, breastfeeding
• Atrial fibrillation (Ventricular Ejection Fraction (VEF) not evaluable at echography)
• Karnofsky index <80%
• Impossibility to obtain informed consent signed
• Left cardiopathies that can be responsible of post-capillar hypertension
• Involvement in another clinical study with an unregistered drug within 30 days prior to this specific study and during the entire course of the study
• Inability to comply with study procedures (linguistic problem, psychiatric problems, dementia, confusional state)
• Known or suspected non compliance drug or alcohol abuse
• Left heart assessment : diastolic and systolic function and valvular structures to exclude a cardiac pathology

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
On the images 82Rb PET/CT rest MBF	at 12 weeks after start of treatment	myocardial blood flow (MBF in mL/min/g) at rest
Analysis of each method of imaging for assessment of myocardial metabolism	at 12 weeks after start of treatment	On the images of au 18F-FDG PET/CT : myocardial ventricular right maximum standardized uptake value (SUVmax)
Analysis of each method of imaging for assessment of myocardial metabolism and endothelial dysfunction	at 12 weeks after start of treatment	On the images of au 18F-FDG PET/CT : myocardial ventricular left maximum standardized uptake value (SUVmax)
On the images 82Rb PET/CT stress MBF	at 12 weeks after start of treatment	myocardial blood flow (MBF in mL/min/g) at pharmacological stress
On the images 82Rb PET/CT, analysis of endothelial dysfunction cold test MBF	at 12 weeks after start of treatment	myocardial blood flow (MBF in mL/min/g) at cold test

Secondary Outcome Measures

Name	Time	Method
Analysis of right heart catheterization parameters PAP	at 12 weeks after start of treatment	PAP
Analysis of clinical parameters NT-pro-BNP	at 12 weeks after start of treatment	plasmatic NT-pro-BNP
Analysis of right heart catheterization parameters PWP	at 12 weeks after start of treatment	PWP
Analysis of right heart catheterization parameters RAP	at 12 weeks after start of treatment	RAP
Analysis of clinical parameters LFT	at 12 weeks after start of treatment	Results of lung function tests
Analysis of clinical parameters NYHA	at 12 weeks after start of treatment	New York Heart Association (NYHA) classification
Analysis of clinical parameters 6-min walk test	at 12 weeks after start of treatment	6-minute walk test

Trial Locations

Locations (1)

Centre Hospitalier Universitaire Vaudois; 🇨🇭 Lausanne, Vaud, Switzerland