TY - JOUR

T1 - Dual Vasopressin Receptor Antagonism to Improve Congestion in Patients With Acute Heart Failure

T2 - Design of the AVANTI Trial

AU - Goldsmith, Steven R

AU - Burkhoff, Daniel

AU - Gustafsson, Finn

AU - Voors, Adriaan

AU - Zannad, Faiez

AU - Kolkhof, Peter

AU - Staedtler, Gerald

AU - Colorado, Pablo

AU - Dinh, Wilfried

AU - Udelson, James E

N1 - Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2021

Y1 - 2021

N2 - BACKGROUND: Loop diuretics are the main treatment for patients with acute heart failure, but are associated with neurohormonal stimulation and worsening renal function and do not improve long-term outcomes. Antagonists to arginine vasopressin may provide an alternative strategy to avoid these effects. The AVANTI study will investigate the efficacy and safety of pecavaptan, a novel, balanced dual-acting V1a/V2 vasopressin antagonist, both as adjunctive therapy to loop diuretics after admission for acute heart failure, and later as monotherapy.METHODS AND RESULTS: AVANTI is a double-blind, randomized phase II study in 571 patients hospitalized with acute heart failure and signs of persistent congestion before discharge. In part A, patients will receive either pecavaptan 30 mg/d or placebo with standard of care for 30 days. In part B, eligible patients will continue treatment or receive pecavaptan or diuretics as monotherapy for another 30 days. The primary end points for part A are changes in body weight and serum creatinine; for part B, changes in body weight and blood urea nitrogen/creatinine ratio.CONCLUSIONS: This study will provide the first evidence that a balanced V1a/V2 antagonist may safely enhance decongestion, both as an adjunct to loop diuretics and as an alternative strategy.TRIAL REGISTRATION NUMBER: NCT03901729.

AB - BACKGROUND: Loop diuretics are the main treatment for patients with acute heart failure, but are associated with neurohormonal stimulation and worsening renal function and do not improve long-term outcomes. Antagonists to arginine vasopressin may provide an alternative strategy to avoid these effects. The AVANTI study will investigate the efficacy and safety of pecavaptan, a novel, balanced dual-acting V1a/V2 vasopressin antagonist, both as adjunctive therapy to loop diuretics after admission for acute heart failure, and later as monotherapy.METHODS AND RESULTS: AVANTI is a double-blind, randomized phase II study in 571 patients hospitalized with acute heart failure and signs of persistent congestion before discharge. In part A, patients will receive either pecavaptan 30 mg/d or placebo with standard of care for 30 days. In part B, eligible patients will continue treatment or receive pecavaptan or diuretics as monotherapy for another 30 days. The primary end points for part A are changes in body weight and serum creatinine; for part B, changes in body weight and blood urea nitrogen/creatinine ratio.CONCLUSIONS: This study will provide the first evidence that a balanced V1a/V2 antagonist may safely enhance decongestion, both as an adjunct to loop diuretics and as an alternative strategy.TRIAL REGISTRATION NUMBER: NCT03901729.

U2 - 10.1016/j.cardfail.2020.10.007

DO - 10.1016/j.cardfail.2020.10.007

M3 - Journal article

C2 - 33188886

VL - 27

SP - 233

EP - 241

JO - Journal of Cardiac Failure

JF - Journal of Cardiac Failure

SN - 1071-9164

IS - 2

ER -