Heart failure & cardiomyopathiesResearch article
IMPROVE-DiCE, a 2-Part, Open-Label, Phase 2a Trial Evaluating the Safety and Effectiveness of Ninerafaxstat in Patients With Cardiometabolic Syndromes
- Phase 2a open-label trial
- 2-part
- single-arm
Authors' conclusion
These mechanistic phase 2a study results show that ninerafaxstat is safely tolerated and improves myocardial energetics in participants with obesity and diabetes without or with clinically manifest HFpEF.
Study context
- Population
- Patients with T2DM and obesity, without (part 1) or with (part 2) heart failure with preserved ejection fraction (HFpEF)
- Participants
- 42 patients
- Comparison
- Part 1 vs Part 2
- Part 1n = 21
- Part 2n = 21
- Outcome
- Myocardial energetics (PCr/ATP) by magnetic resonance spectroscopy, before vs after treatment
Main finding
As reported in the abstract
Myocardial energetics (PCr/ATP) after ninerafaxstat
Part 1 (T2DM + obesity, no HFpEF, 4-8 weeks): change in PCr/ATP
+0.39±0.49 (95% CI, 0.16-0.62); Cohen's d, 0.79; P=0.002
Part 2 (T2DM + obesity + HFpEF, 12 weeks): change in PCr/ATP
+0.15±0.25 (95% CI, 0.03-0.26); Cohen's d, 0.60; P=0.02
Further findings
Myocardial triglyceride (part 1)
- Lower myocardial triglyceride by 34%
- P = 0.03
Systolic augmentation to exercise (part 2)
- Improved systolic augmentation to exercise +1.4 L/min
- P = 0.04
6-minute walk distance (part 2)
- 6-minute walk distance +16 m
- P = 0.02
NYHA class symptom burden (part 2)
- Improved NYHA class symptom burden
Original publication
IMPROVE-DiCE, a 2-Part, Open-Label, Phase 2a Trial Evaluating the Safety and Effectiveness of Ninerafaxstat in Patients With Cardiometabolic Syndromes. Circulation. Published 18 December 2025. doi:10.1161/circulationaha.125.074041
Summarised from the published abstract; every number is checked against it