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

NCT03953989 | Completed Phase 2 DMC

• 1 other identifier: HCMRanIT001
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HCM - Hypertrophic Non-Obstructive Cardiomyopathy

Outcome Measures

Primary Outcomes (3)

• Myocardial Blood Flow during hyperemia ml/min/g

  Change of near maximal hyperemic myocardial blood flow (MBF ml/min/g) after treatment with ranolazine of at least 0.5 ml/min/g. Myocardial perfusion measured with 13N-ammonia and positron emission tomography at rest and during hyperemia; Hyperaemic Myocardial Blood Flow (MBF) measured following i.v. dipyridamole (0.56 mg/Kg in 4 mins)

  At baseline and after 4 months of treatment

• Coronary Flow Reserve (hyperaemic MBF /resting MBF = CFR).

  Change of CFR after treatment with ranolazine for four months

  At baseline and after 4 months of treatment

• Coronary resistance

  Change of Resting coronary resistance (Mean Arterial Pressure rest/ MBF rest) and minimal (during hyperemia) coronary resistance (Mean arterial Pressure hyperemia/ MBF hyperemia)

  At baseline and after 4 months of treatment

Secondary Outcomes (1)

• Symptoms

  through 4 month of treatment

Study Arms (1)

Patients with hypertrophic cardiomyopathy

EXPERIMENTAL

Thestudy is articulated into Screening visit plus other 3 visits. One visit (V2 ) for dose titration. V0 screening eligibility, consent, Medical History, physical examination, BP, ECG, Echocardiography, Biochemistry (haematology, electrolytes, glycaemia, ALS and bilirubin, creatinine and urine-analysis) V1 Baseline PET scan, physical examination, vital signs, and drug supply (500 mg bid). V2 physical examination, safety check, biochemistry, drug compliance and up-titration (750 mg bid), drug supply. V3 (2 months)safety check ,drug supply, drug compliance V4 (4 months, end of treatment) repeat PET scan, physical examination, BP, ECG, drug compliance, safety. Drug of the study Ranolazine PR (prolonged-release) 500 mg 1 tablet bis in die and 750 mg 1 tablet bis in die

Drug: Ranolazine PR (prolonged-release) 500 mg 1 tablet bis in die and 750 mg 1 tablet bis in die

Interventions

Ranolazine PR (prolonged-release) 500 mg 1 tablet bis in die and 750 mg 1 tablet bis in die DRUG

Patients enrolled in the study, at the end of the titration phase will be treated with ranolazine 750 mg or 500 mg, 1 oral tablet twice a day for 4 months on top of standard of care treatment

Also known as: Ranexa

Patients with hypertrophic cardiomyopathy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• IRCCS San Raffaele: lead
• Menarini International Operations Luxembourg SA: collaborator

Study Sites (1)

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

MeSH Terms

Interventions

Ranolazine

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Paolo Camici, MD

  IRCCS Ospedale San Raffaele

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Cardiology

Model Details: A pilot study, one center, open, non-controlled, one group pre-post treatment

Study Record Dates

• First Submitted: May 13, 2019
• First Posted: May 17, 2019
• Study Start: October 1, 2016
• Primary Completion: February 1, 2020
• Study Completion: March 6, 2020
• Last Updated: December 10, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)