Starting soon
Not applicable
Effect of Henagliflozin on Myocardial Fibrosis in Non-Obstructive HCM: A Randomized, Double-Blind, Placebo-Controlled Trial Using 68Ga/18F-FAPI PET/CMR
Condition(s) studied
HCM - Hypertrophic Cardiomyopathy
Investigational drug(s) / intervention(s)
Henagliflozin (SGLT2 Inhibitor)Placebo
Henagliflozin (SGLT2 Inhibitor): This intervention involves the oral administration of Henagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, at a dose of 10 mg once daily for a period of 6 months. Henagliflozin is provided as a film-coated tablet identical in appearance to the matched placebo used in the control arm. The intervention is administered in a double-blind manner as an add-on to stable standard background therapy for non-obstructive hypertrophic cardiomyopathy. This study specifically investigates the potential anti-fibrotic effects of Henagliflozin on active myocardial fibrosis, as quantified by novel FAPI PET/CMR imaging, in a patient population without diabetes mellitus.
Placebo: This intervention involves the oral administration of a matched placebo tablet once daily for a period of 6 months. The placebo is manufactured to be identical in appearance (size, shape, color, coating), packaging, and administration schedule to the active comparator, Henagliflozin 10 mg tablet. It contains no active pharmaceutical ingredient. The intervention is administered in a double-blind manner as an add-on to stable standard background therapy for non-obstructive hypertrophic cardiomyopathy, serving as the control to isolate and evaluate the specific pharmacological effects of the SGLT2 inhibitor.
Study summary
his is a single-center, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the effect of Henagliflozin (an SGLT2 inhibitor) on myocardial fibrosis burden in patients with non-obstructive hypertrophic cardiomyopathy (nHCM). The study will use 68 68 Ga/ 18 18 F-FAPI PET/CMR imaging to quantitatively assess changes in active fibroblast activity after 6 months of treatment. A total of 150 eligible adult patients with nHCM (FAPI-positive at baseline, NYHA class I-III) will be enrolled and randomized in a 1:1 ratio to either the Henagliflozin group (10 mg once daily) or the placebo group for a 6-month treatment period. The primary endpoint is the change in myocardial FAPI target-to-background ratio (ΔTBR) at 6 months. Secondary endpoints include changes in FAPI SUVmax, FAPI burden percentage (FAV%), cardiac structure and function parameters, 6-minute walk distance, NYHA classification, NT-proBNP levels, and quality-of-life scores. Exploratory analyses will assess clinical events over 12 months, such as heart failure hospitalization, atrial fibrillation, ventricular arrhythmias, and cardiovascular death. The study employs stratified block randomization based on baseline FAPI burden, central randomization and blinding via IWRS, independent core laboratory imaging evaluation, and an intention-to-treat analytical approach. It aims to provide early evidence for the anti-fibrotic effect of Henagliflozin in nHCM and to validate FAPI-PET/CMR as an imaging biomarker for fibrosis activity.
Eligibility
Inclusion Criteria:
1. Aged 18 years or older, regardless of gender.
2. Meets the diagnostic criteria for non-obstructive hypertrophic cardiomyopathy (HCM):
* Confirmed diagnosis of HCM by cardiac magnetic resonance (CMR) or echocardiography (left ventricular wall thickness ≥15 mm, or ≥13 mm in the presence of a family history of HCM).
* Exclusion of patients in whom left ventricular hypertrophy is primarily attributable to hypertensive heart disease, as assessed by a cardiology specialist based on clinical and imaging evidence.
* Exclusion of other identifiable causes of secondary myocardial hypertrophy (e.g., valvular heart disease, storage cardiomyopathies).
* Left ventricular outflow tract (LVOT) gradient \<30 mmHg at rest or under provocation, as assessed by echocardiography or CMR.
3. Willing to undergo FAPI PET/CMR examination and complete imaging evaluations.
4. Baseline FAPI PET/CMR scan shows positive FAPI uptake: myocardial FAPI target-to-background ratio (TBR) ≥1.3, using the ascending aorta blood pool as the background reference.
5. Capable of understanding and signing the informed consent form, and agrees to participate in the study, accept randomization, and comply with follow-up visits.
6. New York Heart Association (NYHA) functional class I-III.
Exclusion Criteria:
1. Significant left ventricular outflow tract obstruction (resting or provoked LVOT pressure gradient ≥30 mmHg).
2. Coexistence of other identifiable causes of myocardial hypertrophy, including:
* Predominant or persistent hypertensive heart disease;
* Severe aortic stenosis or other significant valvular heart disease;
* Infiltrative or storage cardiomyopathies (e.g., Fabry disease, amyloidosis);
* Ischemic heart disease (e.g., severe coronary artery disease).
3. Overt decompensated heart failure or NYHA functional class IV.
4. Unstable, serious arrhythmias (e.g., sustained ventricular tachycardia, recent cardioversion for atrial fibrillation).
5. Recent (within 3 months) cardiac surgery or interventional procedure.
6. ALT or AST \>3 times the upper limit of normal (ULN), OR total bilirubin (Tbil) \>2 times ULN, OR ketonuria/ketonemia, OR eGFR \<30 mL/min/1.73m², OR creatine kinase (CK) \>3 times ULN.
7. Concurrent other severe systemic disease with a life expectancy of less than 1 year.
8. Pregnant or breastfeeding women.
9. History of allergy to the study drug or any contraindication to its use.
10. Any other condition deemed by the investigator to make the subject unsuitable for participation.
Primary outcome measure(s)
- Change in Myocardial FAPI Target-to-Background Ratio (ΔTBR) — From baseline to 6 months post-intervention
The primary outcome is the change in myocardial FAPI uptake quantified by the target-to-background ratio (TBR) on FAPI PET/CMR imaging. TBR is calculated as the ratio of the mean standardized uptake value (SUVmean) in the myocardium to that in the ascending aortic blood pool. The difference in TBR from baseline to 6 months post-intervention (ΔTBR) will be compared between the Henagliflozin and placebo groups. This measure directly reflects changes in active fibroblast activity and myocardial fibrosis burden.
Trial sites (1)
| Facility | City | Region | Status |
|---|
| Shanghai East Hospital |
Shanghai |
Shanghai Municipality |
|
More Shanghai East Hospital trials in China
Other trials for the same condition