Effects of Ranolazine on Coronary Microvascular Dysfunction in Patients With Hypertrophic Cardiomyopathy
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|ClinicalTrials.gov Identifier: NCT03953989|
Recruitment Status : Completed
First Posted : May 17, 2019
Last Update Posted : December 10, 2020
|Condition or disease||Intervention/treatment||Phase|
|HCM - Hypertrophic Non-Obstructive Cardiomyopathy||Drug: Ranolazine PR (prolonged-release) 500 mg 1 tablet bis in die and 750 mg 1 tablet bis in die||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||A pilot study, one center, open, non-controlled, one group pre-post treatment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study Assessing the Effects of Ranolazine on Coronary Microvascular Dysfunction in Patients With Hypertrophic Cardiomyopathy|
|Actual Study Start Date :||October 2016|
|Actual Primary Completion Date :||February 1, 2020|
|Actual Study Completion Date :||March 6, 2020|
Experimental: Patients with hypertrophic cardiomyopathy
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
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
Other Name: Ranexa
- 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)
- Symptoms [ Time Frame: through 4 month of treatment ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03953989
|IRCCS Ospedale San Raffaele|
|Milan, Italy, 20132|
|Principal Investigator:||Paolo Camici, MD||IRCCS Ospedale San Raffaele|