Does the use of empagliflozin improve exercise capacity in patients with hypertrophic cardiomyopathy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

22 Jun 2022 → ongoing

Decision date (initial)

2024-11-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Medical Research Agency

External identifiers

EU CT number

2024-517643-31-00

EudraCT number

2021-005395-19

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

Main objective: to assess whether the use of empagliflozin 10 mg daily for 12 months improves exercise capacity in patients with hypertrophic cardiomyopathy

Secondary objectives 1

1. Main objective: to assess whether the use of empagliflozin 10 mg daily for 12 months improves exercise capacity in patients with hypertrophic cardiomyopathy and reduced left ventricular ejection fraction (EF <50%)

Conditions and MedDRA coding

Hypertrophic cardiomyopathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. written, voluntary informed consent to participate in the study
2. diagnosis of hypertrophic cardiomyopathy
3. age ≥ 18 years

Exclusion criteria 32

1. Refusal to consent to participate in the study
2. Diagnosis of diabetes
3. 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
4. ICD or cardiac pacemaker (for a group of patients in whom cardiac magnetic resonance study will be performed; n=100)
5. Planned implantation of cardiac resynchronization therapy (CRT of CRT-D) in the following 12 months
6. Life expectancy below 12 months
7. Pregnancy (currently or planned in the following 12 months)
8. Breast feeding
9. Age below 18 years
10. Recurrent genito-urinary tract infections in the past or currently (For recurrent infections are defined as: two or more infections in the past two months months)
11. Urosepsis in the history
12. Impaired renal function, defined as eGFR < 30 mL/min/1.73 m2 (CKD-EPI)cr or requiring dialysis,
13. Other contraindications to the use of empagliflozin
14. Musculo-skeletal or neurologic diseases that make it unable to perform cardiopulmonary exercise testing
15. Heart transplant recipient or listed for heart transplant
16. Implanted left ventricular assist device
17. Any severe (obstructive or regurgitant) valvular heart disease expected to lead to surgery during the trial in the Investigator's opinion
18. 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
19. Atrial fibrillation or atrial flutter with a resting heart rate > 110 bpm documented by ECG at screeining
20. Systolic blood pressure (SBP) ≥ 180 mmHg at randomization
21. Symptomatic hypotension and/or a SBP < 100 mmHg at screeining or randomization
22. 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
23. 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
24. Haemoglobin < 9 g/dl at screening
25. 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
26. Gastrointestinal (GI) surgery or GI disorder that could interfere with absorption of trial medication in the investigator's opinion
27. 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
28. History of ketoacidosis
29. Patients who must or wish to continue the intake of any drug considered likely to interfere with the safe conduct of the trial
30. 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)
31. 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
32. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. A test of the null hypothesis that the mean VO 2 max measured 12 months after randomization is the same in the treatment group and the placebo group;
2. A null hypothesis test that the mean KCCQ-OS value measured 12 months after randomization is the same in the treatment group and the placebo group.

Secondary endpoints 1

1. The secondary objective of the trial is to test the null hypothesis that the mean value of the VO 2 max measured 12 months after randomization is the same in the treatment group treated group and the placebo group among patients with reduced left ejection fraction ventricle.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy

Sponsor organisation

Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy

Address

Alpejska 42

City

Warsaw

Postcode

04-628

Country

Poland

Scientific contact point

Organisation

Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy

Contact name

Clinical Research Support Centre Information Desk

Public contact point

Organisation

Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy

Contact name

Clinical Research Support Centre Information Desk

Third parties 1

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications