HCM - Hypertrophic Non-Obstructive CardiomyopathyPhase 2NCT03953989

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

A Phase 2 study testing Ranolazine PR (prolonged-release) 500 mg 1 tablet bis in die and 750 mg 1 tablet bis in die in people with HCM - Hypertrophic Non-Obstructive Cardiomyopathy, run by IRCCS San Raffaele at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: HCM - Hypertrophic Non-Obstructive Cardiomyopathy
What is being tested?: Ranolazine PR (prolonged-release) 500 mg 1 tablet bis in die and 750 mg 1 tablet bis in die
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 26 participants
Where: 1 siteItaly
Study dates: Oct 2016to 6 Mar 2020
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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;

Who cannot join

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

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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

Trial locations and contacts

1 site in 1 country.

Italy1 site

IRCCS Ospedale San Raffaele
Milan, 20132

Other trials in Italy

About this study

Official title: A Pilot Study Assessing the Effects of Ranolazine on Coronary Microvascular Dysfunction in Patients With Hypertrophic Cardiomyopathy

Read the detailed description

This pilot study aimed at assessing the effects of treatment with ranolazine, on top of optimal standard medical therapy (according to international guidelines), on microvascular dysfunction using PET in patients with HCM.

Thirty months of enrolment are foreseen. 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. Visit 0,1,2,3 may be performed 3 days before or 3 days after the planned date. Visit 4 and final PET scan may be performed 15 days before or 15 days after the planned date.

This is a superiority study. The sample size calculation is based on the ANOVA model, but the statistical analysis will be performed applying the ANCOVA model for the absence of data on the correlation between basal and end of study values of the primary variable studied. As previously reported (Camici et al. J Am Coll Cardiol 1991; 17:879-86) maximum (i.e. during dipyridamole stress) MBF is severely blunted in HCM (1.63±0.58 mL/min/g) compared to control subjects (2.99±1.06 mL/min/g). For the primary end-point of the study using a two-sided test at 5% significance level, with a power of 90% and a SD of ± 0.7 mL/min/gr, in order to detect a change of 0.5 mL/min/gr in maximum MBF before and after treatment, 24 patients valid per protocol are required.

Conditions: HCM - Hypertrophic Non-Obstructive Cardiomyopathy
Being tested: Ranolazine PR (prolonged-release) 500 mg 1 tablet bis in die and 750 mg 1 tablet bis in die

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Ranolazine PR (prolonged-release) 500 mg 1 tablet bis in die and 750 mg 1 tablet bis in dieDrug
Also called Ranexa
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

Study groups in NCT03953989
Study group	Role	What they receive
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 Receives: Drug: Ranolazine PR (prolonged-release) 500 mg 1 tablet bis in die and 750 mg 1 tablet bis in die

What is being measured

The primary outcome is the main question the study is designed to answer.

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)
Measured: 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
Measured: 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)
Measured: At baseline and after 4 months of treatment

Secondary outcomes (1)

Symptoms
Number of participants with absence of symptoms accountable for drug intolerability ,assessed through customized questionnaire. If symptoms are accountable for drug intolerability are referred, the patient will come back to 500 mg/bid.
Measured: through 4 month of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 20166 Mar 2020

First posted17 May 2019
Study startOct 2016
Primary completion1 Feb 2020
Study completion6 Mar 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for HCM - Hypertrophic Non-Obstructive CardiomyopathyStudies of the same condition, open and under way.
More trials run by IRCCS San RaffaeleThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: A pilot study, one center, open, non-controlled, one group pre-post treatment
Masking: None (open label)
Enrolment: 26 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03953989
Sponsor's protocol ID: HCMRanIT001
Status last verified: Dec 2020
First submitted: 13 May 2019
Last updated: 10 Dec 2020
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1
Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HTX-001
Nonobstructive Hypertrophic Cardiomyopathy
Not yet recruitingPhase 4
Dapagliflozin in Patients With Non-Obstructive Hypertrophic Cardiomyopathy: A Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial
Nonobstructive Hypertrophic Cardiomyopathy
RecruitingPhase 2
A Trial to Evaluate the Efficacy and Safety of Ninerafaxstat in Patients With Symptomatic Non-obstructive Hypertrophic Cardiomyopathy
Non-obstructive Hypertrophic Cardiomyopathy
Enrolling by invitationPhase 2/3
Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of Aficamten in Adults With HCM
Symptomatic Hypertrophic Cardiomyopathy (HCM)
Not yet recruiting
Coronary Sinus Reducer Objective Impact on SymptoMs, Ischaemia and miCrovascular Resistance in Non-obstructive Hypertrophic CardioMyopathy
Hypertrophic Cardiomyopathy

All HCM - Hypertrophic Non-Obstructive Cardiomyopathy trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pilot Study Assessing the Effects of Ranolazine on Coronary Microvascular Dysfunction in Patients With Hypertrophic Cardiomyopathy
ClinicalTrials.gov ID: NCT03953989
Acronym / sponsor ID: HCMRanIT001
Conditions: HCM - Hypertrophic Non-Obstructive Cardiomyopathy
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 26 participants (actual)
Lead sponsor: IRCCS San RaffaeleUniversity, hospital or other
Collaborators: Menarini International Operations Luxembourg SA
Study start: Oct 2016 (actual)
Primary completion: 1 Feb 2020 (actual)
Study completion: 6 Mar 2020 (actual)
First posted: 17 May 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: A pilot study, one center, open, non-controlled, one group pre-post treatment

Arm	Type	Receives
Patients with hypertrophic cardiomyopathy	Experimental	Drug: Ranolazine PR (prolonged-release) 500 mg 1 tablet bis in die and 750 mg 1 tablet bis in dieThestudy 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

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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);

Key exclusion criteria (24 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Ranolazine PR (prolonged-release) 500 mg 1 tablet bis in die and 750 mg 1 tablet bis in dieAlso: RanexaPatients 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	Drug	Patients with hypertrophic cardiomyopathy

Primary outcome

Myocardial Blood Flow during hyperemia ml/min/g
Time frame: At baseline and after 4 months of treatment
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)
Coronary Flow Reserve (hyperaemic MBF /resting MBF = CFR).
Time frame: At baseline and after 4 months of treatment
Change of CFR after treatment with ranolazine for four months
Coronary resistance
Time frame: At baseline and after 4 months of treatment
Change of Resting coronary resistance (Mean Arterial Pressure rest/ MBF rest) and minimal (during hyperemia) coronary resistance (Mean arterial Pressure hyperemia/ MBF hyperemia)

1 secondary outcome

Symptoms
Time frame: through 4 month of treatment

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2020.
Individual participant dataSharing planned: No

Related trials for HCM - Hypertrophic Non-Obstructive Cardiomyopathy

RecruitingPhase 1
Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HTX-001
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Not yet recruitingPhase 4
Dapagliflozin in Patients With Non-Obstructive Hypertrophic Cardiomyopathy: A Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial
Nonobstructive Hypertrophic Cardiomyopathy
RecruitingPhase 2
A Trial to Evaluate the Efficacy and Safety of Ninerafaxstat in Patients With Symptomatic Non-obstructive Hypertrophic Cardiomyopathy
Non-obstructive Hypertrophic Cardiomyopathy
Enrolling by invitationPhase 2/3
Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of Aficamten in Adults With HCM
Symptomatic Hypertrophic Cardiomyopathy (HCM)
Not yet recruiting
Coronary Sinus Reducer Objective Impact on SymptoMs, Ischaemia and miCrovascular Resistance in Non-obstructive Hypertrophic CardioMyopathy
Hypertrophic Cardiomyopathy

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Paolo Camici, MD principal investigator

IRCCS Ospedale San Raffaele

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Myocardial Blood Flow during hyperemia ml/min/g (time frame: At baseline and after 4 months of treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03953989.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2020.