A pilot study assessing the effects of Ranolazine on small heart vessels dysfunction in patients with hypertrophic cardiomyopathy

Phase 1

• Conditions: Hypertrophic cardiomyopathy; MedDRA version: 20.0Level: PTClassification code 10020871Term: Hypertrophic cardiomyopathySystem Organ Class: 10010331 - Congenital, familial and genetic disorders; MedDRA version: 20.1Level: LLTClassification code 10020204Term: HOCM Hypertrophic obstructive cardiomyopathySystem Organ Class: 10010331 - Congenital, familial and genetic disorders; MedDRA version: 20.0Level: LLTClassification code 10020203Term: HOCMSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; MedDRA version: 20.0Level: LLTClassification code 10020876Term: Hypertrophic obstructive cardiomyopathySystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2015-004402-42-IT
• Lead Sponsor: OSPEDALE SAN RAFFAELE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-09-09
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1.Male and female gender.
2.Patients who fulfil conventional echocardiographic criteria for the diagnosis of HCM: maximum LV wall thickness = 15 mm;
3.Patients aged > 18 years and < 80 years;
4.Absence of severe resting LV outflow tract obstruction (peak gradient = 50 mmHg);
5.Sinus rhythm; accepted isolated Supraventricular and Ventricular Premature Beats (VPB);
6.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);
7.Females of childbearing potential or within two years from the menopause must have a negative urine pregnancy test;
8.Ability to give written informed consent prior to enrolment into the study;

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 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

Exclusion Criteria

1.severe resting LV outflow tract obstruction (peak gradient > 50 mmHg)
2.Females of childbearing potential not using highly effective contraception;
3.Presence of known coronary artery disease (CAD);
4.Presence of Chronic Obstructive Airways Disease;
5.Asthma;
6.Other causes of microvascular dysfunction including long-standing history of arterial hypertension, diabetes, uncontrolled dyslipidemia;
7.Body mass index >32 kg/m2; < 17 kg/m2
8.Overt LV systolic dysfunction with end-stage progression (LV-EF <50%);
9.Concomitant administration of potent CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, voriconazol, posaconazol, HIV protease inhibitors, clarithromycin, telithromycin, nefazodone);
10.Patients treated with sotalol, dronedarone, class I antiarrhythmics or other QT-prolonging drugs; stable treatment with amiodarone is permitted;
11.Patients with QTc (Bazett’s formula) at baseline = 450 ms males; = 470 msec females
12.Any clinically relevant haematological or biochemical abnormality on routine screening, according to Investigator’s judgment;
13.Severe concurrent pathology, including terminal illness (cancer, AIDS, etc.);
14.Severe renal impairment defined as GFR < 29 mL/min/1.73 m2 or creatinine level > 2.5 mg/dL or BUN >60 mg/dL;
15.Moderate or severe hepatic impairment or hepatic insufficiency defined as SGOT or SGPT > 2 times greater than upper limit of normal of the local laboratory or total serum bilirubin > 1.5 times greater than normal upper limit of the local laboratory;
16.Dementia, psychosis, alcoholism (>350 g ethanol/week) or chronic abuse of medicaments, drugs or psychoactive substances;
17.Claustrophobia;
18.Females who are pregnant or lactating;
19.Conditions which in the Investigator’s opinion may interfere with the study’s execution or due to which the patient should not participate for safety reasons;
20.Risk of poor patient cooperation;
21.Participation into a clinical study = 2 months before enrolment;
22.Inability or unwillingness to issue the informed consent;
23.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);
24.Concomitant use of Atorvastatin (>80 mg daily);
25.Concomitant use of >1000 mg daily dose of metformin during the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified