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Eur Heart J. 2017 Aug 7;38(30):2364-2373. doi: 10.1093/eurheartj/ehx196.

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).

Author information

Department of Emergency Medicine, Indiana University School of Medicine & Indianapolis EMS, Indianapolis, IN, USA.
SUNY Stonybrook School of Medicine, New York, NY, USA.
Vanderbilt University, Nashville, TN, USA.
Momentum Research Inc., Durham, NC, USA.
University of Alberta, Edmonton, Alberta, Canada.
National and Kapodistrian University of Athens, School of Medicine, Heart Failure Unit, Department of Cardiology, Attikon University Hospital, Athens, Greece.
Wayne State University School of Medicine and Cardiovascular Research Institute, Detroit, MI, USA.
Cardiology, University of Brescia, Brescia, Italy.
Clinical Military Hospital, Medical University, Wroclaw, Poland.
Section of Cardiology, San Francisco Veterans Affairs Medical Center and School of Medicine, University of California San Francisco, San Francisco, CA, USA.
University of Groningen, Groningen, the Netherlands.
Allergan plc (Forest Labs), Jersey City, NJ, USA.
Trevena Inc, King of Prussia, PA, USA.
Duke University School of Medicine and the Duke Clinical Research Institute, Durham, NC, USA.



Currently, no acute heart failure (AHF) therapy definitively improves outcomes. Reducing morbidity and mortality from acute heart failure (AHF) remains an unmet need. TRV027 is a novel 'biased' ligand of the angiotensin II type 1 receptor (AT1R), selectively antagonizing the negative effects of angiotensin II, while preserving the potential pro-contractility effects of AT1R stimulation. BLAST-AHF was designed to determine the safety, efficacy, and optimal dose of TRV027 to advance into future studies.

Methods and results:

BLAST-AHF was a multi-centre, international, randomized, double-blind, placebo-controlled, parallel group, phase IIb dose-ranging study, enrolling patients with AHF into 4 groups: placebo, 1, 5, or 25 mg/h of TRV027. Treatment was by IV infusion for 48-96 h. The primary composite endpoint was comprised of the following: (i) time from baseline to death through day 30, (ii) time from baseline to heart failure re-hospitalization through day 30, (iii) the first assessment time point following worsening heart failure through day 5, (iv) change in dyspnea visual analogue scale (VAS) score calculated as the area under the curve (AUC) representing the change from baseline over time from baseline through day 5, and (v) length of initial hospital stay (in days) from baseline. Analyses were by modified intention-to-treat. Overall, 621 patients were enrolled. After 254 patients, a pre-specified interim analysis resulted in several protocol changes, including a lower blood pressure inclusion criterion as well as a new allocation scheme of 2:1:2:1, overweighting both placebo, and the 5 mg/h dose. TRV027 did not confer any benefit over placebo at any dose with regards to the primary composite endpoint or any of the individual components. There were no significant safety issues with TRV027.


In this phase IIb dose-ranging AHF study, TRV027 did not improve clinical status through 30-day follow-up compared with placebo.


Acute heart failure; Angiotensin-II; Biased ligand; Clinical trials

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