Effects of Ranolazine on Coronary Microvascular Dysfunction in Patients With Hypertrophic Cardiomyopathy

• Status: Completed
• Trial end date: 2020-03-06
• Target enrollment: 0
• Participant gender: All

Summary

To demonstrate the efficacy of ranolazine in improving coronary microvascular and diastolic dysfunction in patients affected by HCM evaluating changes in maximum (i.e. during dipyridamole-induced coronary vasodilatation) myocardial blood flow (MBF) measured by PET at baseline and after 4 months of treatment with ranolazine in patients with non obstructive HCM.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: IRCCS San Raffaele
• Collaborator: Menarini International Operations Luxembourg SA
• Treatments: Ranolazine

Criteria

Inclusion Criteria:

• Male and female gender (females of childbearing potential must be using highly effective contraceptive precautions such as implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence or vasectomised partner);

• Females of childbearing potential or within two years from the menopause must have a negative urine pregnancy test;

• Patients which fulfill conventional echocardiographic criteria for the diagnosis of HCM: maximum LV wall thickness ≥ 15 mm;

• Patients aged > 18 years and < 80 years;

• Sinus rhythm accepted isolated Supraventricular and Ventricular Premature Beats (VPB);

• Absence of severe resting LV outflow tract obstruction (peak gradient ≤ 50 mmHg);

• Written informed consent prior to enrolment into the study;

Exclusion Criteria:

• Females of childbearing potential not using highly effective contraceptive precautions;

• Presence of known coronary artery disease (CAD);

• Presence of Chronic Obstructive Airways Disease;

• Asthma;

• Other causes of microvascular dysfunction including long-standing history of arterial hypertension, diabetes, uncontrolled dyslipidemia;

• Body mass index >32 kg/m2; < 17 kg/m2

• Overt LV systolic dysfunction with end-stage progression (LV-EF <50%);

• Concomitant administration of potent CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, voriconazol, posaconazol, HIV protease inhibitors, clarithromycin, telithromycin, nefazodone);

• Patients treated with sotalol, dronedarone, class I antiarrhythmics (see appendix 4) or other QT-prolonging drugs; stable treatment with amiodarone is permitted;

• Patients with QTc (Bazett's formula) at baseline ≥ 450 ms males; ≥470 msec females;

• Any clinically relevant haematological or biochemical abnormality on routine screening, according to Investigator's judgment;

• Severe concurrent pathology, including terminal illness (cancer, AIDS, etc.);

• Severe renal impairment defined as GFR < 29 mL/min/1.73m2 or creatinine level > 2.5 mg/dL or BUN >60 mg/dL;

• Moderate or severe hepatic impairment or hepatic insufficiency defined as SGOT or SGPT > 2 times greater than normal upper limit of the local laboratory or total serum bilirubin > 1.5 times greater than normal upper limit of the local laboratory;

• Dementia, psychosis, alcoholism (>350 g ethanol/week) or chronic abuse of medicaments, drugs or psychoactive substances;

• Claustrophobia;

• Females who are pregnant or lactating;

• Conditions that in the Investigator's opinion may interfere with the study's execution or due to which the patient should not participate for safety reasons;

• Risk of poor patient cooperation;

• Participation in a clinical study ≤ 2 months before enrolment;

• Inability or unwillingness to issue the informed consent;

• Concomitant use of > 20 mg daily dose of Simvastatin during the study (in case of patients taking simvastatin > 20 mg daily, the switch to other statins not metabolized by the CYP3A4 could be considered);

• Concomitant use of Atorvastatin (> 80 mg daily)

• Concomitant use of > 1000 mg daily dose of metformin during the study