Dual Vasopressin Receptor Antagonism to Improve Congestion in Patients With Acute Heart Failure: Design of the AVANTI Trial.
Congestive heart failure
decongestion
diuretic
vasopressin
Journal
Journal of cardiac failure
ISSN: 1532-8414
Titre abrégé: J Card Fail
Pays: United States
ID NLM: 9442138
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
10
08
2020
revised:
07
10
2020
accepted:
20
10
2020
pubmed:
15
11
2020
medline:
20
8
2021
entrez:
14
11
2020
Statut:
ppublish
Résumé
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. 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. 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. NCT03901729.
Sections du résumé
BACKGROUND
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
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
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
BACKGROUND
NCT03901729.
Identifiants
pubmed: 33188886
pii: S1071-9164(20)31483-4
doi: 10.1016/j.cardfail.2020.10.007
pii:
doi:
Substances chimiques
Antidiuretic Hormone Receptor Antagonists
0
Diuretics
0
Receptors, Vasopressin
0
Sodium Potassium Chloride Symporter Inhibitors
0
Banques de données
ClinicalTrials.gov
['NCT03901729']
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
233-241Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.