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

Endothelial Dysfunction Clinical Trial

Official title:

Effect of Endothelin Receptor Antagonist Bosentan in Glucose Metabolism of the Myocardium and Coronary Dependant Endothelial Vasoreactivity Measured by 18F-FDG PET / CT and 82Rb PET / CT in Patients With PAH or CTEPH

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02970851
• Other study ID #: 08/12
• Status: Terminated
• Start date: April 2013
• Est. completion date: December 31, 2018

Study information

• Verified date: March 2020
• Source: University of Lausanne Hospitals
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: December 31, 2018
• Est. primary completion date: December 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Endothelial Dysfunction
• Myocardial Dysfunction

Locations

Country	Name	City	State
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne	Vaud

Sponsors (1)

Lead Sponsor	Collaborator
University of Lausanne Hospitals

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Analysis of each method of imaging for assessment of myocardial metabolism	On the images of au 18F-FDG PET/CT : myocardial ventricular right maximum standardized uptake value (SUVmax)	Baseline
Primary	Analysis of each method of imaging for assessment of myocardial metabolism	myocardial ventricular right maximum standardized uptake value (SUVmax) on the images of au 18F-FDG PET/CT	at 4 weeks after start of treatment
Primary	Analysis of each method of imaging for assessment of myocardial metabolism	On the images of au 18F-FDG PET/CT : myocardial ventricular right maximum standardized uptake value (SUVmax)	at 6 weeks after start of treatment
Primary	Analysis of each method of imaging for assessment of myocardial metabolism	On the images of au 18F-FDG PET/CT : myocardial ventricular right maximum standardized uptake value (SUVmax)	at 12 weeks after start of treatment
Primary	On the images 82Rb PET/CT rest MBF	myocardial blood flow (MBF in mL/min/g) at rest	Baseline
Primary	On the images 82Rb PET/CT rest MBF	myocardial blood flow (MBF in mL/min/g) at rest	at 4 weeks after start of treatment
Primary	On the images 82Rb PET/CT rest MBF	myocardial blood flow (MBF in mL/min/g) at rest	at 6 weeks after start of treatment
Primary	On the images 82Rb PET/CT rest MBF	myocardial blood flow (MBF in mL/min/g) at rest	at 12 weeks after start of treatment
Primary	On the images 82Rb PET/CT stress MBF	myocardial blood flow (MBF in mL/min/g) at pharmacological stress	Baseline
Primary	On the images 82Rb PET/CT stress MBF	myocardial blood flow (MBF in mL/min/g) at pharmacological stress	at 4 weeks after start of treatment
Primary	On the images 82Rb PET/CT stress MBF	myocardial blood flow (MBF in mL/min/g) at pharmacological stress	at 6 weeks after start of treatment
Primary	On the images 82Rb PET/CT stress MBF	myocardial blood flow (MBF in mL/min/g) at pharmacological stress	at 12 weeks after start of treatment
Primary	On the images 82Rb PET/CT, analysis of endothelial dysfunction cold test MBF	myocardial blood flow (MBF in mL/min/g) at cold test	Baseline
Primary	On the images 82Rb PET/CT, analysis of endothelial dysfunction cold test MBF	myocardial blood flow (MBF in mL/min/g) at cold test	at 4 weeks after start of treatment
Primary	On the images 82Rb PET/CT, analysis of endothelial dysfunction cold test MBF	myocardial blood flow (MBF in mL/min/g) at cold test	at 6 weeks after start of treatment
Primary	On the images 82Rb PET/CT, analysis of endothelial dysfunction cold test MBF	myocardial blood flow (MBF in mL/min/g) at cold test	at 12 weeks after start of treatment
Primary	Analysis of each method of imaging for assessment of myocardial metabolism and endothelial dysfunction	On the images of au 18F-FDG PET/CT : myocardial ventricular left maximum standardized uptake value (SUVmax)	Baseline
Primary	Analysis of each method of imaging for assessment of myocardial metabolism and endothelial dysfunction	On the images of au 18F-FDG PET/CT : myocardial ventricular left maximum standardized uptake value (SUVmax)	at 4 weeks after start of treatment
Primary	Analysis of each method of imaging for assessment of myocardial metabolism and endothelial dysfunction	On the images of au 18F-FDG PET/CT : myocardial ventricular left maximum standardized uptake value (SUVmax)	at 6 weeks after start of treatment
Primary	Analysis of each method of imaging for assessment of myocardial metabolism and endothelial dysfunction	On the images of au 18F-FDG PET/CT : myocardial ventricular left maximum standardized uptake value (SUVmax)	at 12 weeks after start of treatment
Secondary	Analysis of right heart catheterization parameters PAP	pulmonary arterial pressure (PAP)	at screening
Secondary	Analysis of right heart catheterization parameters PAP	PAP	at 12 weeks after start of treatment
Secondary	Analysis of right heart catheterization parameters RAP	right atrial pressure (RAP)	at screening
Secondary	Analysis of right heart catheterization parameters RAP	RAP	at 12 weeks after start of treatment
Secondary	Analysis of right heart catheterization parameters PWP	pulmonary wedge pressure (PWP)	at screening
Secondary	Analysis of right heart catheterization parameters PWP	PWP	at 12 weeks after start of treatment
Secondary	Analysis of clinical parameters NYHA	NYHA classification	at screening
Secondary	Analysis of clinical parameters NYHA	New York Heart Association (NYHA) classification	at 12 weeks after start of treatment
Secondary	Analysis of clinical parameters 6-min walk test	6-minute walk test	at screening
Secondary	Analysis of clinical parameters 6-min walk test	6-minute walk test	at 12 weeks after start of treatment
Secondary	Analysis of clinical parameters LFT	Results of lung function tests	at screening
Secondary	Analysis of clinical parameters LFT	Results of lung function tests	at 12 weeks after start of treatment
Secondary	Analysis of clinical parameters NT-pro-BNP	plasmatic N terminal - pro - Brain Natriuretic Peptide (NT-pro-BNP)	at screening
Secondary	Analysis of clinical parameters NT-pro-BNP	plasmatic NT-pro-BNP	at 12 weeks after start of treatment

External Links

•   abstract poster presentation about present study