The Use of Empagliflozin in Patients With Hypertrophic Cardiomyopathy

Official Summary

The proposed intervention will be administration of empagliflozin at a standard dose of 10 mg daily for a period of 12 months. Patients with diagnosed diabetes will be excluded from the study. Patients (n = 250) will be randomized in a double-blind fashion to empagliflozin or placebo group. The primary endpoint of the study will be the change in peak oxygen uptake (VO2 max) measured in a cardiopulmonary exercise test. VO2max is an objective indicator of physical performance and will be evaluated before and after empagliflozin or placebo treatment.

Eligibility Requirements

• Minimum Age: 18 Years
• Maximum Age: 70 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: TRIPLE
• Enrollment: 250 participants

Study Arms

• Empagliflozin group (ACTIVE_COMPARATOR)
  Patients in the empagliflozin group will receive 10 mg of empagliflozin once daily for 12 months
• Control group (PLACEBO_COMPARATOR)
  Patients in the control group will receive placebo once daily for 12 months

Interventions

• DRUG: Empagliflozin 10 MG — The proposed intervention will be administration of empagliflozin at a standard dose of 10 mg daily for a period of 12 months. Patients with diagnosed diabetes will be excluded from the study. Patients (n = 250) will be randomized in a double-blind fashion to empagliflozin or placebo group.
• DRUG: Placebo — The proposed intervention will be administration of placebo for a period of 12 months. Patients (n = 250) will be randomized in a double-blind fashion to empagliflozin or placebo group.

Primary Outcomes

• Primary Outcome: Change in peak VO2 measured in the cardiopulmonary exercise testing AND Change in 23-item Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) range from 0 to 100, with higher scores indicating better health status. (12 months)

Secondary Outcomes

• Secondary outcome: Change in peak VO2 measured in the cardiopulmonary exercise testing in patients with reduced left ventricular ejection fraction (EF <50%) (12 months)

Eligibility Criteria

Inclusion Criteria:

* written, voluntary informed consent to participate in the study
* diagnosis of hypertrophic cardiomyopathy
* age ≥ 18 years

Exclusion Criteria:

* refusal to consent to participate in the study
* diagnosis of diabetes
* patients with hypertrophic obstructive cardiomyopathy requiring interventional treatment (maximal LVOT gradient ≥ 50 mmHg), and who are in III-IV NYHA functional class, despite of the treatment with maximal tolerated doses
* refusal to consent to participate in the study
* diagnosis of diabetes
* patients with hypertrophic obstructive cardiomyopathy requiring interventional treatment (maximal LVOT gradient ≥ 50 mmHg), and who are in III-IV NYHA functional class, despite of the treatment with maximal tolerated doses
* ICD or cardiac pacemaker (for a group of patients in whom cardiac magnetic resonance study will be performed; n=100)
* planned implantation of cardiac resynchronization therapy (CRT of CRT-D) in the following 12 months
* life expectancy below 12 months
* pregnancy (currently or planned in the following 12 months)
* breast feeding
* age below 18 years
* recurrent genito-urinary tract infections in the past or currently
* urosepsis in the history
* Impaired renal function, defined as eGFR \< 30 mL/min/1.73 m2 (CKD-EPI)cr or requiring dialysis,
* other contraindications to the use of empagliflozin
* musculo-skeletal or neurologic diseases that make it unable to perform cardiopulmonary exercise testing
* heart transplant recipient or listed for heart transplant
* implanted left ventricular assist device
* Any severe (obstructive or regurgitant) valvular heart disease expected to lead to surgery during the trial in the Investigator's opinion
* Acute decompensated HF (exacerbation of chronic HF) requiring intravenous (i.v.) diuretics, i.v. inotropes or i.v. vasodilators, or left ventricular assist device within 1 week from discharge to screening, and during screening period until randomization
* Atrial fibrillation or atrial flutter with a resting heart rate \> 110 bpm documented by ECG at screeining
* Systolic blood pressure (SBP) ≥ 180 mmHg at randomization
* Symptomatic hypotension and/or a SBP \< 100 mmHg at screeining or randomization
* Chronic pulmonary disease requiring home oxygen, oral steroid therapy or hospitalisation for exacerbation within 12 months, or significant chronic pulmonary disease in the Investigator's opinion, or primary pulmonary arterial hypertension
* Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) at screening
* Haemoglobin \< 9 g/dl at screening
* Major surgery (major according to the investigator's assessment) performed within 90 days prior to screening, or scheduled major elective surgery (e.g. hip replacement ) within 90 days after screening
* Gastrointestinal (GI) surgery or GI disorder that could interfere with absorption of trial medication in the investigator's opinion
* Any documented active or suspected malignancy or history of malignancy within 2 years prior to screening, except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of uterine cervix or low risk prostate cancer
* History of ketoacidosis
* Patients who must or wish to continue the intake of any drug considered likely to interfere with the safe conduct of the trial
* Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s), or receiving other investigational treatment(s)
* Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable trial subject or unlikely to complete the trial
* Any other clinical condition that would jeopardise patients safety while participating in this trial, or may prevent the subject from adhering to the trial protocol

Trial Locations

• Medical University of Bialystok, Bialystok, Poland
• National Institute of Cardiology, Warsaw, Poland

Study Officials

• Mateusz Śpiewak, MD, PhD — PRINCIPAL_INVESTIGATOR
  National Institute of Cardiology, Department of Radiology, Magnetic Resonance Unit
• Mariusz Kłopotowski, MD, PhD — PRINCIPAL_INVESTIGATOR
  National Institute of Cardiology, Department of Cardiology and Interventional Angiology
• Karol Kamiński, Professor — PRINCIPAL_INVESTIGATOR
  Medical University of Bialystok, Department of Population Medicine and Lifestyle Diseases Prevention

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