Biased Ligand of the Angiotensin Receptor Study in Acute Heart Failure (BLAST-AHF) Study
CO-PI: Peter Pang, MD
BLAST-AHF is an international, multi-center, randomized, placebo controlled, double-blind parallel group, dose finding study of TRV027 vs. placebo, both in addition to standard therapy in 618 AHF patients. TRV027 is a biased ligand of the angiotensin II type I receptor (AT1R), a G-protein coupled receptor. Rather than block all of the GPCR downstream signals, which occurs with classical ARB’s, TRV027 antagonizes stimulation of the GPCR, while recruiting Beta-arrestin. In pre-clinical and early human and chronic HF models, this Nobel Prize winning chemistry demonstrated balanced vasodilator activity while enhancing cardiac output and preserving renal function. Importantly, RAAS blockade has not been previously well tested in AHF, despite being the cornerstone of chronic HF management. We hypothesized that the novel pharmacology of TRV027 would yield benefits in AHF. The Phase IIB results of BLAST-AHF were recently presented at the ESC-HFA congress in Florence, Italy. There were 621 patients enrolled and BLAST-AHF failed to find a significant difference in the primary endpoint between TRV027 and placebo.