Efficacy and Safety of TRC041266 in Patients With Heart Failure, LVEF ≥40%, Diastolic Dysfunction and Type 2 Diabetes Mellitus

NCT04507347 | Withdrawn Phase 3 DMC

• 1 other identifier: CT/P004/HF/19/03_01
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will be conducted as a randomized, multi-centre, double-blind, parallel-group, placebo-controlled study in patients receiving SoC therapy. Eligible participants will be randomized in a ratio of 1:1 to receive either test product, TRC041266 1500 mg or matching placebo twice daily for 48 weeks

Conditions

Chronic Stable Heart Failure

Outcome Measures

Primary Outcomes (1)

• Primary composite endpoint consisting of incidence of cardiac mortality and/or number of worsening of heart failure and/or change from baseline to week 48 in functional capacity

  Worsening of heart failure will be comprising of hospitalization for heart failure, or emergency visits for heart failure, or sustained increase in dose of diuretics Functional capacity shall be assessed by Physical Dimension-Minnesota Living with Heart Failure Questionnaire, and supervised 6-minute walk distance (measured in meters)

  48 weeks

Study Arms (2)

Test product

EXPERIMENTAL

Eligible participants will be randomized to receive test product, TRC041266 1500 mg twice daily for 48 weeks.

Drug: TRC041266

Placebo product

PLACEBO COMPARATOR

Eligible participants will be randomized to receive matching placebo twice daily for 48 weeks.

Drug: Placebo

Interventions

TRC041266 DRUG

TRC041266 sachet 1500 mg strengths

Test product

Placebo DRUG

TRC041266 sachet 1500 mg matching placebo

Placebo product

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged 40-70 years (both inclusive)
• Type 2 diabetes mellitus on stable hypoglycemic therapy for \>1 month
• Diagnosed with heart failure\* according to 2016 ESC Guidelines for Chronic Heart Failure for at least 6 months and receiving SoC for at least 3 months
• \*HF - a clinical syndrome characterized by typical symptoms (e.g. breathlessness, ankle swelling and fatigue) that may be accompanied by signs (e.g. elevated jugular venous pressure, pulmonary crackles and peripheral edema) caused by a structural and/or functional cardiac abnormality, resulting in a reduced cardiac output and/or elevated intra-cardiac pressures at rest or during stress
• Participants with LVEF ≥40% including HFpEF according to ESC criteria, diagnosed by ECHO, confirmed by core ECHO laboratory AND having moderate to severe diastolic dysfunction as described in 'Classification of Diastolic Dysfunction'
• Treatment with stable# doses of loop diuretics for \>1 month at a daily dose of furosemide of ≥40 mg or equivalent (1 mg of bumetanide or 10 mg of torasemide) or alternatively, 20 mg furosemide + mineralocorticoid receptor antagonist or equivalent (0.5 mg of bumetanide + mineralocorticoid receptor antagonist or 5 mg of torasemide + mineralocorticoid receptor antagonist) or equivalent as per the regional SoC
• On stable# doses of beta-blockers for \>1 month
• No exceptions are allowed to the above rule if LVEF is ≤50% OR the patient has coronary artery disease,
• If LVEF is \>50% and the patient is NOT KNOWN to have coronary disease, they may be included if they are not taking beta-blockers provided there is no indication to use them such as rate control for atrial fibrillation or hypertension
• Participants willing to give written informed consent (prior to any study-related procedures being performed) and able to adhere to the study restrictions and assessments schedule
• stable = a dose no lower than half the current dose and not greater than double the current dose

You may not qualify if:

• Known hypersensitivity to any ingredient of the study medication
• Heart failure caused by myocarditis, cor-pulmonale, congenital heart disease,constrictive pericarditis, idiopathic hypertrophic or restrictive cardiomyopathy, amyloid heart disease or rheumatic heart disease
• Significant valvular heart disease including severe mitral regurgitation or left ventricular (LV) aneurysm as judged by the investigator and/or echo core-laboratory
• History of MI, CABG surgery, PCI or other major surgery, stroke or TIA in past 6 months
• Patients who are anticipated to require coronary revascularization; patients with angina must be evaluated by a cardiologist to determine the need for revascularization
• NYHA class IV
• A score of less than 12 points on adequately explained and administered MLHFQ points 2, 3, 4, 5, 7, 8, 12 and 13
• Hospitalization for heart failure with overnight stay in the past 3 months
• Participants with symptomatic or sustained VT\* in the past 6 months and planned for cardiac resynchronization therapy (CRT) or implantation of ICD for the duration of the study.
• \* Participant with symptomatic or sustained VT having an implantable cardioverter defibrillator (ICD) can be included in the study.
• Atrial fibrillation or flutter with a resting ventricular rate \>110 beats per minute
• Unable to walk or has any contraindication to 6-minute walk test or those in whom longest distance walked in supervised 6 minutes (6MWTD) at baseline was \<100 m or \>350m
• Systolic BP \< 100 mmHg or ≥ 160 mmHg or Diastolic BP ≥ 100 mmHg at screening
• Hb \<12 g/dL
• HbA1c \>11%

Sponsors & Collaborators

• Torrent Pharmaceuticals Limited: lead

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind, Placebo-controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2020
• First Posted: August 11, 2020
• Study Start: June 1, 2021
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2024
• Last Updated: December 27, 2022

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share