Clinical effectiveness of tolvaptan in patients with acute decompensated heart failure and renal failure: design and rationale of the AQUAMARINE study.
OBJECTIVE
Over half of all admitted acute decompensated heart failure (ADHF) patients have renal failure. Although diuretics represent the mainstay of treatment strategy even in this population, there are unmet needs for safer and more effective treatment. Tolvaptan is a vasopressin-2 receptor antagonist, and we hypothesized that adding tolvaptan to standard diuretic therapy would be more effective in ADHF patients with renal function impairment.


METHODS
The Answering question on tolvaptan's efficacy for patients with acute decompensated heart failure and renal failure (AQUAMARINE) is a multicenter, randomized controlled clinical trial, which will enroll 220 patients from 17 hospitals in Japan. ADHF patients whose estimated glomerular filtration rate is above 15 and below 60 mL/min/1.72 m(2) will be randomly assigned within 6 h after admission to usual care with furosemide or tolvaptan add-on therapy. Primary endpoint is achieved urine output within 48 h. Secondary endpoints include dyspnea relief measured by 7-points Likert scale, incidence of worsening renal function, dose of furosemide used within 48 h, and changes of brain natriuretic peptide.


CONCLUSIONS
This study is the first multicenter study in Japan to evaluate clinical effectiveness of tolvaptan add-on therapy in ADHF patients with renal failure. The results of this study address the treatment strategy of this high-risk population (UMIN Clinical Trial Registry Number: UMIN000007109).
Department of Cardiology, Kameda Medical Center, 929 Higashi-chou, Kamogawa-City, Chiba, 296-8602, Japan, yuya8950@gmail.com.
Yuya
Y
Matsue
Makoto
M
Suzuki
Wataru
W
Nagahori
Kazuki
K
Yoshida
Yuko
Y
Onishi
Yasuhiro
Y
Satoh
Yuichi
Y
Ono
Toshihiko
T
Nishioka
Makoto
M
Noda
Kaoru
K
Sugi
Sho
S
Torii
Tamotsu
T
Tejima
Harumizu
H
Sakurada
Satoshi
S
Yamaguchi
Kaoru
K
Okishige
Hiroyuki
H
Fujii
Atsushi
A
Takahashi
D000208:Acute Disease; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000008:administration & dosage / Q000627:therapeutic use*; D004232:Diuretics / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005665:Furosemide / Q000008:administration & dosage / Q000627:therapeutic use; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007564:Japan; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D012107:Research Design; D000077602:Tolvaptan
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D004232:Diuretics; D020097:Natriuretic Peptide, Brain; D000077602:Tolvaptan; D005665:Furosemide