Chronic Stable Heart FailurePhase 3NCT04507347
Efficacy and Safety of TRC041266 in Patients With Heart Failure, LVEF ≥40%, Diastolic Dysfunction and Type 2 Diabetes Mellitus
A Phase 3 study testing TRC041266 in people with Chronic Stable Heart Failure, run by Torrent Pharmaceuticals Limited.
Trial 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 Read more about this study
- Who is it for?
- Ages 40 to 70 years
- Conditions the study is for
- Chronic Stable Heart Failure
- What is being tested?
- TRC041266
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jun 2021to Jun 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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'
- NT-proBNP (N-terminal fragment of brain natriuretic peptide) 250-3500 pg/mL (both inclusive) For participants who have atrial fibrillation, the inclusion qualification would be 750- 3500 pg/ml (both inclusive)
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- 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
Who cannot join
- 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
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- 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%
- eGFR <30 mL/min/1.73m2 (calculated by Modification of Diet in Renal Disease formula) [eGFR (mL/min/1.73 m²) = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African American) (conventional units)]
- Liver enzymes (AST or ALT) exceeding 3 times the upper limit of normal range at screening and considered clinically significant by the investigator
- Current hyponatremia (Na+ <130 mmol/L) or hyperkalemia (K+ >5.5 mmol/L)
- Participants on insulin as monotherapy for diabetes
- History of gastrointestinal disorder (e.g. malabsorption syndrome) that could interfere with study drug absorption
- Known to have positive test for HIV, Hepatitis B, Hepatitis C at the time of screening
- History of malignancy in last 3 years other than basal cell carcinoma
- Pregnant or lactating women, or female of childbearing potential, who are neither surgically sterilized nor willing to use reliable contraceptive methods (double barrier methods or intrauterine device)
- Men with partners of childbearing potential not willing to use reliable contraception methods
- Current participation (including prior 30 days) in any other therapeutic clinical trial
- In the opinion of the investigator, any finding which would interfere with the objectives of the study, patient is unable to cooperate with any study procedures, unlikely to adhere to the study procedures, keep appointments, or plan to relocate during the study
About this study
Official title: Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicentre Study to Evaluate the Efficacy and Safety of TRC041266 Compared to Placebo in Patients With Chronic Stable Heart Failure, an LVEF ≥40%, Moderate to Severe Diastolic Dysfunction and Type 2 Diabetes Mellitus
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
Read the detailed description
HFpEF is associated with high morbidity and mortality and the prevalence is on the rise globally. Diabetics are at increased risk of developing HFpEF.
There is no evidence based therapy to improve the disease condition and its associated functional incapacity. Some of the recently concluded trials, PARAGON-HF, EMPERIAL-PRESERVED, failed to demonstrate benefit and it is regarded as an area with high unmet need.
Phase 2 results have demonstrated that in diabetic patients with heart failure having LVEF >30% and receiving guideline-indicated therapy with RAS inhibitors and β-blockers, TRC4186 has the potential to improve worsening of heart failure, functional status, cardiac diastolic function and has no adverse effect on cardiac mortality.
Therefore, TRC041266, the decanoic acid co-crystal of TRC4186 is an innovative product for the management of heart failure with LVEF≥40% in diabetic patients which is expected to modify the underlying disease at multiple levels and confer benefit as add-on to standard of care.
The current phase 3 study has been planned based on the results of the phase 2 trial which demonstrated that the TRC4186 2000 mg/day (in two divided doses; BD) administered orally for 48 weeks resulted in significant improvement in QoL measured by PD-MLHFQ, diastolic dysfunction measured by E/e' and reduction in HF hospitalization.
The dose level to be used in the present study is based on the assessment of safety, efficacy and PK data obtained from phase 1 and 2 studies. In the phase 2 study, a dose response was observed with a trend towards improvement at 500 mg/day dose of TRC4186, and clinically and statistically significant improvement was seen at 2000 mg/day (1000 mg BD). There was plateauing of the response beyond the dose of 2000 mg/day. Hence, the choice of optimal dose of TRC4186 being considered is lower than 2000 mg/day and in between 500 and 2000 mg/day, i.e., 1500 mg/day (750 mg BD). The total daily dose of TRC041266 which would be equivalent to 1500 mg/day of TRC4186, is TRC041266 3000 mg/day, to be administered in two divided doses,i.e., 1500 mg BD.
- Conditions
- Chronic Stable Heart Failure
- Being tested
- TRC041266, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TRC041266Drug
TRC041266 sachet 1500 mg strengths
PlaceboDrug
TRC041266 sachet 1500 mg matching placebo
| Study group | Role | What they receive |
|---|---|---|
| Test product | Experimental | Eligible participants will be randomized to receive test product, TRC041266 1500 mg twice daily for 48 weeks. Receives: Drug: TRC041266 |
| Placebo product | Placebo comparator | Eligible participants will be randomized to receive matching placebo twice daily for 48 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2020
- Study startJun 2021 (estimated)
- Primary completionJun 2024 (estimated)
- Study completionJun 2024 (estimated)
Why it stopped: Study halted prematurely, prior to enrollment of first participant hence study withdrawn
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Stable Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Torrent Pharmaceuticals Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04507347
- Sponsor's protocol ID
- CT/P004/HF/19/03_01
- Status last verified
- Aug 2020
- First submitted
- 16 Jul 2020
- Last updated
- 27 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicentre Study to Evaluate the Efficacy and Safety of TRC041266 Compared to Placebo in Patients With Chronic Stable Heart Failure, an LVEF ≥40%, Moderate to Severe Diastolic Dysfunction and Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT04507347
- Acronym / sponsor ID
- CT/P004/HF/19/03_01
- Conditions
- Chronic Stable Heart Failure
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study halted prematurely, prior to enrollment of first participant hence study withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Torrent Pharmaceuticals LimitedIndustry (pharma, biotech, devices)
- Study start
- Jun 2021 (estimated)
- Primary completion
- Jun 2024 (estimated)
- Study completion
- Jun 2024 (estimated)
- First posted
- 11 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
HFpEF is associated with high morbidity and mortality and the prevalence is on the rise globally. Diabetics are at increased risk of developing HFpEF.
There is no evidence based therapy to improve the disease condition and its associated functional incapacity. Some of the recently concluded trials, PARAGON-HF, EMPERIAL-PRESERVED, failed to demonstrate benefit and it is regarded as an area with high unmet need.
Phase 2 results have demonstrated that in diabetic patients with heart failure having LVEF >30% and receiving guideline-indicated therapy with RAS inhibitors and β-blockers, TRC4186 has the potential to improve worsening of heart failure, functional status, cardiac diastolic function and has no adverse effect on cardiac mortality.
Therefore, TRC041266, the decanoic acid co-crystal of TRC4186 is an innovative product for the management of heart failure with LVEF≥40% in diabetic patients which is expected to modify the underlying disease at multiple levels and confer benefit as add-on to standard of care.
The current phase 3 study has been planned based on the results of the phase 2 trial which demonstrated that the TRC4186 2000 mg/day (in two divided doses; BD) administered orally for 48 weeks resulted in significant improvement in QoL measured by PD-MLHFQ, diastolic dysfunction measured by E/e' and reduction in HF hospitalization.
The dose level to be used in the present study is based on the assessment of safety, efficacy and PK data obtained from phase 1 and 2 studies. In the phase 2 study, a dose response was observed with a trend towards improvement at 500 mg/day dose of TRC4186, and clinically and statistically significant improvement was seen at 2000 mg/day (1000 mg BD). There was plateauing of the response beyond the dose of 2000 mg/day. Hence, the choice of optimal dose of TRC4186 being considered is lower than 2000 mg/day and in between 500 and 2000 mg/day, i.e., 1500 mg/day (750 mg BD). The total daily dose of TRC041266 which would be equivalent to 1500 mg/day of TRC4186, is TRC041266 3000 mg/day, to be administered in two divided doses,i.e., 1500 mg BD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Test product | Experimental | Drug: TRC041266Eligible participants will be randomized to receive test product, TRC041266 1500 mg twice daily for 48 weeks. |
| Placebo product | Placebo comparator | Drug: PlaceboEligible participants will be randomized to receive matching placebo twice daily for 48 weeks. |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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'
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TRC041266TRC041266 sachet 1500 mg strengths | Drug | Test product |
| PlaceboTRC041266 sachet 1500 mg matching placebo | Drug | Placebo product |
Primary outcome
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
Time frame: 48 weeks
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)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing TRC041266 in people with Chronic Stable Heart Failure, run by Torrent Pharmaceuticals Limited.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 27 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2022.