Biased ligand of the angiotensin II type 1 receptor in patients with acute heart failure: a randomized, double-blind, placebo-controlled, phase IIB, dose ranging trial (BLAST-AHF)
Key result
TRV027 shows no benefit over placebo for 30-day composite clinical status.
- n=621
Why the study?
Currently, no acute heart failure therapy definitively improves outcomes, and reducing morbidity and mortality remains an unmet need.
Does TRV027 improve clinical outcomes in patients with acute heart failure?
Population
621 patients with AHF
Comparison
TRV027 (1, 5, or 25 mg/h IV infusion) vs placebo
Design
Multicentre international randomized double-blind placebo-controlled parallel-group phase IIb dose-ranging study
Follow-up
30 days
Authors
Discussion
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Member takes
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“We are very disappointed that TRV027 failed to show the hoped for benefits to patients in the BLAST-AHF study. We will continue to analyze the data to further understand the outcome, but believe the study was well conducted and has answered the questions it was designed to test.”
“It is always disappointing when an investigational product fails to support a promising hypothesis in a clinical trial.”
“The BLAST-AHF trial is testing the impact of TRV027 on a range of important clinical measures in acute heart failure using an innovative composite endpoint. Current therapies are not proven and can worsen the angiotensin-mediated pathophysiology driving AHF. TRV027, with its novel mode of action, directly targets this core pathophysiology, which may improve patient outcomes. Positive results from this study would help inform the optimal design of registration studies.”
Implication
TRV027 should not be pursued clinically at tested doses; confirms neutral effect on primary composite endpoint in this RCT.
Key Points
- To assess the safety, efficacy, and optimal dosing of TRV027 in acute heart failure patients.
- Multi-centre, international, randomized, double-blind, placebo-controlled trial.
- 621 patients enrolled and treated with IV TRV027 or placebo for 48-96 hours.
- Primary endpoint included death, heart failure re-hospitalization, and VAS score changes over 30 days.
- TRV027 showed no benefit over placebo in the primary composite endpoint after 30 days.
- There were no significant safety issues associated with TRV027 treatment.
Study Design
Type
RCT (n=621)
Blinding
Double-blind
Randomization
2:1:2:1 allocation scheme
Multicenter
Yes
Structured PICO
Does TRV027 improve clinical outcomes in patients with acute heart failure?
P
Population
621 patients with acute heart failure treated with TRV027 or placebo and followed for 30 days.
I
Intervention
TRV027 (1, 5, or 25 mg/h) via IV infusion for 48-96 h
C
Comparator
Placebo
O
Outcome
Composite of time from baseline to death through day 30, time from baseline to heart failure re-hospitalization through day 30, first assessment time point following worsening heart failure through day 5, change in dyspnea visual analogue scale (VAS) score AUC through day 5, and length of initial hospital staycomposite
TRV027, a novel biased ligand of the angiotensin II type 1 receptor, did not improve clinical outcomes in patients with acute heart failure.
Cite This Study
Pang et al. (2017) conducted an RCT in Acute heart failure (n=621). TRV027 vs. Placebo was evaluated on Composite of time to death through day 30, time to heart failure re-hospitalization through day 30, worsening heart failure through day 5, change in dyspnea VAS score AUC through day 5, and length of initial hospital stay. TRV027 at doses of 1, 5, or 25 mg/h did not confer any benefit over placebo for the primary composite endpoint of clinical status through 30-day follow-up.