METHODS AND RESULTS: This phase II, 8-week, multicentre, double-blind, parallel-group study randomized participants (2:1) to receive
lixivaptan 100 mg or placebo once daily (in addition to standard HF
therapy).
Body weight and cardiovascular assessments were made at baseline, Day 1 (not cardiovascular), Weeks 1, 2, 4, and 8, and 7 days post-treatment. The Trail-making Test, part B (TMT-B) and the Medical Outcomes Survey 6-item cognitive function scale (MOS-6) were assessed at baseline and Week 4. The study randomized 170 participants (
lixivaptan, n = 111; placebo, n = 59). Most (97.1%) were receiving pharmacological
therapy for HF at baseline. Demographic characteristics were generally similar between the two groups.
Body weight decreased significantly from baseline to Day 1 with
lixivaptan vs. placebo (least-square mean change ± standard error: - 0.38 ± 0.08 kg vs. +0.13 ± 0.11 kg; P < 0.001) and at Weeks 1, 2, and 4 (P < 0.01). Cardiovascular changes were generally similar in both groups, though orthopnoea and dyspnoea improved in the
lixivaptan group vs. placebo. The TMT-B and MOS-6 showed no significant differences between groups.
Lixivaptan was well tolerated-thirst and
polyuria occurred more frequently vs. placebo.
CONCLUSIONS: In outpatients with HF and volume overload,
lixivaptan 100 mg once daily, when added to standard
therapy, reduced
body weight, improved dyspnoea and orthopnoea, and was well tolerated.
TRIAL REGISTRATION: NCT01055912.