Effect of Henagliflozin on Myocardial Fibrosis in Non-Obstructive HCM: A Randomized, Double-Blind, Placebo-Controlled Trial Using 68Ga/18F-FAPI PET/CMR

NCT07294495 | Not Yet Recruiting

• 1 other identifier: 2025286
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HCM - Hypertrophic Cardiomyopathy

Keywords

PET/MR; FAPI; Hypertrophic Cardiomyopathy

Outcome Measures

Primary Outcomes (1)

• Change in Myocardial FAPI Target-to-Background Ratio (ΔTBR)

  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.

  From baseline to 6 months post-intervention

Secondary Outcomes (10)

• Change in Myocardial FAPI Maximum Standardized Uptake Value (ΔSUVmax)

  From baseline to 6 months post-intervention

• Change in FAPI Activity Volume Percentage (ΔFAV%)

  From baseline to 6 months post-intervention

• Change in Left Ventricular Ejection Fraction (ΔLVEF)

  From baseline to 6 months post-intervention

• Change in Left Ventricular Mass Index (ΔLVMi)

  From baseline to 6 months post-intervention

• Change in Late Gadolinium Enhancement Extent (ΔLGE)

  From baseline to 6 months post-intervention

Other Outcomes (6)

• Significant Worsening of Cardiac Function or Onset of Heart Failure

  Throughout the 12-month study period

• New Onset or Recurrence of Atrial Fibrillation/Atrial Flutter

  Throughout the 12-month study period

• Sustained or Non-Sustained Ventricular Tachycardia

  Throughout the 12-month study period

Study Arms (2)

Henagliflozin (SGLT2 Inhibitor)

EXPERIMENTAL

Participants randomized to this arm will receive a once-daily oral dose of Henagliflozin (10 mg tablet) for a total intervention period of 6 months. Henagliflozin is a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. All participants will continue their stable standard background therapy for hypertrophic cardiomyopathy throughout the study.

Drug: Henagliflozin (SGLT2 Inhibitor)

Placebo

PLACEBO COMPARATOR

Participants randomized to this arm will receive a once-daily oral dose of a matching placebo tablet for a total intervention period of 6 months. The placebo is identical in appearance, packaging, and administration schedule to the active drug. All participants will continue their stable standard background therapy for hypertrophic cardiomyopathy throughout the study.

Drug: Placebo

Interventions

Henagliflozin (SGLT2 Inhibitor) DRUG

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.

Henagliflozin (SGLT2 Inhibitor)

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years or older, regardless of gender.
• 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).
• Left ventricular outflow tract (LVOT) gradient \<30 mmHg at rest or under provocation, as assessed by echocardiography or CMR.
• Willing to undergo FAPI PET/CMR examination and complete imaging evaluations.
• 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.
• Capable of understanding and signing the informed consent form, and agrees to participate in the study, accept randomization, and comply with follow-up visits.
• New York Heart Association (NYHA) functional class I-III.

You may not qualify if:

• Significant left ventricular outflow tract obstruction (resting or provoked LVOT pressure gradient ≥30 mmHg).
• 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).
• Overt decompensated heart failure or NYHA functional class IV.
• Unstable, serious arrhythmias (e.g., sustained ventricular tachycardia, recent cardioversion for atrial fibrillation).
• Recent (within 3 months) cardiac surgery or interventional procedure.
• 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.
• Concurrent other severe systemic disease with a life expectancy of less than 1 year.
• Pregnant or breastfeeding women.
• History of allergy to the study drug or any contraindication to its use.
• Any other condition deemed by the investigator to make the subject unsuitable for participation.

Sponsors & Collaborators

• Shanghai East Hospital: lead

Study Sites (1)

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200120, China

Location

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic

Interventions

henagliflozin; Sodium-Glucose Transporter 2 Inhibitors

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs

Central Study Contacts

Jie Ding, MD.

CONTACT

86-021-38804518; dingjie940406@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind trial where the participant, the care provider (investigator), and the outcomes assessor (including imaging analysts and statisticians) are all masked to group assignment. The active drug (Henagliflozin) and the matched placebo are identical in appearance, packaging, and labeling. The randomization code is maintained by an independent central pharmacy and the Interactive Web Response System. Unblinding occurs only in medical emergencies or after database lock.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study employs a two-arm, parallel-group, randomized controlled trial model. Eligible participants are randomly assigned in a 1:1 ratio to one of two parallel treatment arms. Both arms receive their assigned intervention (active drug or matched placebo) concurrently over the same fixed period of 6 months, followed by a common follow-up schedule. The outcomes are compared between these independent, parallel groups at pre-defined time points.

Study Record Dates

• First Submitted: December 8, 2025
• First Posted: December 19, 2025
• Study Start: January 7, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)