Heart failure & cardiomyopathies
Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of CRD-740, a PDE9 Inhibitor, in Chronic Heart Failure
Primary result · Change in plasma cGMP from baseline (AUC 0–6 h)Result — go to the resultLeast squared mean difference 26.5% 95% CI 7.8–45.1Authors' conclusion
In this initial phase 2 trial, PDE9 inhibition with CRD-740 was well tolerated and resulted in elevations of plasma and urinary cGMP on top of standard care, including sacubitril/valsartan, supporting the potential of PDE9 inhibition to enhance the beneficial effects of the natriuretic peptide receptor-cGMP pathway incremental to existing heart failure treatments.
Study context
- Population
- Heart failure and reduced ejection fraction (HFrEF) >6 months, NYHA II/III, EF ≤40%, elevated NT-proBNP
- Participants
- 60 participants
- Comparison
- CRD-740 vs placebo
- CRD-740n = 40
- Placebon = 20reference
- Primary endpoint
- Change in plasma cGMP (pharmacodynamic)
- Follow-up
- Week 4
Methodological detailsphase 2, double-blind, placebo-controlled, 2:1 randomisation
- Phase 2
- Double-blind
- Placebo-controlled
- 2:1 randomisation
Primary result
Change in plasma cGMP from baseline (AUC 0–6 h)
Least squared mean difference
26.5%
95% CI 7.8–45.1
P = 0.003
Change by group
CRD-740
19.1% increase
SD 26.9%
Placebo
8.8% decrease
SD 31.3%
As reported in the abstract
Further findings
Urinary cyclic guanosine monophosphate (cGMP)
- Increase with CRD-740 at day 1
- P = 0.012
- Increase with CRD-740 at week 2
- P = 0.014
- Increase with CRD-740 at week 4
- P = 0.09
Safety
SBP, hypotension, serious adverse events
- No significant between-group differences
Original publication
Summarised from the published abstract; every number is checked against it