A Dose Titration Study to Assess the Effects of SAR407899 in Patients with MVA and/or Persistent Stable Angina despite Angiographically Successful PCI
- Conditions
- MedDRA version: 20.0Level: PTClassification code 10072685Term: Microvascular coronary artery diseaseSystem Organ Class: 10007541 - Cardiac disordersTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]Microvascular coronary artery disease
- Registration Number
- EUCTR2016-000629-38-SE
- Lead Sponsor
- SANOFI-AVENTIS RECHERCHE ET DEVELOPPEMENT
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 260
- Male or female patient not at childbearing potential =18 year-old or legal age of majority.
- Female patient if she has undergone sterilization at least 3 months earlier or is postmenopausal.
- Post-menopausal status is defined by having no menses for 12 months without an alternative medical cause.
- In females not treated with hormonal replacement therapy (HRT), menopausal status is confirmed by a high follicle stimulating hormone (FSH) level greater than 40 IU/L.
- In females on HRT and whose menopausal status is in doubt (ie, in women aged less than 45 years), a highly effective contraception methods will be required. Contraception should be used during the whole study and for at least seven days corresponding to time needed to eliminate study treatment.
- Symptomatic stable angina pectoris (typical or atypical symptoms with an average of at least biweekly episodes over the past month).
- Patients with non-obstructive (<50% stenosis) coronary arteries or intermediate stenosis (between 50 and 70%) should have fractional flow reserve (FFR) >0.80 or instantaneous wave-free ratio (iFR) >0.89 on angiogram, documented within the previous 24 months*. In patients with stenting, a minimum diameter stenosis of <10% is required.
or
Coronary computed tomography angiography (CCTA) with finding of non-obstructive coronary arteries within the past 24 months* in patients without previous percutaneous coronary intervention (PCI).
*Note: in cases of clinically suspected progression of atherosclerosis as per the Investigator, a more contemporary (i.e., 6 months) evidence should be provided.
or
CCTA performed during screening period, with finding of non-obstructive coronary arteries, in patients diagnosed with microvascular angina (MVA) and stable angina without previous PCI who did not have a coronary angiogram or CCTA in the previous 24 months but between 24 months to 5 years.
- Baseline global coronary flow reserve (CFR) (measured during the study) assessed by 13Nammonia or 82Rubidium positron emission tomography (PET) scan <2.0.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 183
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 77
- Any use of nitrates (except short-acting nitrates) and/or dipyridamole and/or phosphodiesterase type 5 (PDE 5) inhibitors within one week prior to baseline PET scan or anticipated to be used during the study.
- Esophageal dysmotility or esophagitis.
- Patients with acute coronary syndrome (ACS) (myocardial infarction [MI] and/or unstable angina) in previous 3 months.
- Unsuccessful or incomplete coronary revascularization with residual obstructive stenosis or coronary artery disease (CAD) progression in native vessels as documented on invasive coronary angiography (=50% stenosis) within 24 months of enrollment.
- Percutaneous coronary intervention performed at the time of an ACS (MI or unstable angina) in the previous 12 months.
- Recent PCI within the past 3 months.
- Patients with history of coronary artery bypass grafting (CABG).
- Recent (=3 months) major surgery (ie, valvular surgery, surgery for congenital heart disease), stroke, transient ischemic attack [TIA], sustained ventricular arrhythmia, clinically significant structural heart disease (moderate-severe valvular disease, hypertrophic cardiomyopathy, congenital heart disease, pulmonary hypertension).
- Regional local flow abnormal perfusion defects at baseline PET scan*.
*Note: if contemporary evidence with invasive coronary angiography or coronary computed tomography angiography (CCTA) demonstrates non-obstructive coronary arteries or if the regional local flow abnormal perfusion defect on PET scan is consistent with previous studies then patient qualifies for the study.
- Patients with cardiac conduction abnormalities (second or third degree atrioventricular [AV] block, sick sinus syndrome, symptomatic bradycardia, sinus node disease) except in patients fitted with a functioning pacemaker.
- History or known carotid stenosis:
- Carotid stenosis (>50%)
or
- History of carotid stenosis in patients with previous symptoms.
- Contraindication or known hypersensitivity to adenosine or regadenoson.
- Contraindication to aminophylline.
- Contraindication to vasodilator stress PET scan and/or CCTA if CCTA needed during screening.
- Inability to discontinue treatment with methylxanthines treatment within 24 hours prior to PET scan.
- Patient unable to read, understand and fill a questionnaire without any help (eg, partially visually impaired or blind).
- Systolic blood pressure (SBP) <110 mmHg at baseline.
- Presence at baseline of symptomatic orthostatic hypotension (SBP decrease of 20 mmHg or more at Minute 3 or Minute 5 between seated and standing position), or asymptomatic orthostatic hypotension with a decrease in SBP equal or greater than 30 mmHg at Minute 3 or Minute 5 when changing from the seated to the standing position.
- Renal impairment with estimated glomerular filtration rate (eGFR) <50 mL/min/1.73 m2 at screening and baseline.
- Drug-induced liver injury related criteria:
- Underlying hepatobiliary disease.
- Alanine Aminotransferase (ALT) >3 times the upper limit of normal (ULN).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method