• Vandana S Mathur, Jayant Kumar, Paul W Crawford, Howard Hait, Thomas Sciascia, and TR02 Study Investigators.
• Mathur Consulting, Woodside, California, USA.
• Am. J. Nephrol. 2017 Jan 1; 46 (6): 450-458.

BackgroundPruritus is a distressing hallmark of the uremic condition, affecting approximately 60% of hemodialysis patients. Abnormal endogenous opioid ligand activity at μ and κ-opioid receptors has been postulated as a mechanism in uremic pruritus. Nalbuphine is a μ-opioid antagonist and κ-opioid agonist.MethodsIn this multicenter, randomized, double-blind, placebo-controlled trial, 373 hemodialysis patients with moderate or severe uremic pruritus were randomized in a 1: 1:1 ratio to nalbuphine extended-release tablets 120 mg (NAL 120), 60 mg (NAL 60), or placebo and treated for 8 weeks. Three hundred seventy-one were analyzed for efficacy. The primary endpoint was the change from baseline to treatment weeks 7 and 8 in itching intensity on a Numerical Rating Scale (NRS, 0 [no itching]; 10 [worst possible itching]) using an intent-to-treat approach. The aim was to evaluate the safety and antipruritic efficacy of NAL.ResultsThe mean duration of itching was 3.2 years. From a baseline NRS of 6.9 (1.5), the mean NRS declined by 3.5 (2.4) and by 2.8 (2.2) in NAL 120 mg and the placebo groups, respectively (p = 0.017). There was no evidence of tolerance. A trend for less sleep disruption due to itching (p = 0.062, NAL 120 vs. placebo) was also observed. There were no significant differences between NAL 60 vs. placebo. Serious adverse events occurred in 6.7, 12.7, and 15.4% in the NAL 120, NAL 60, and placebo groups respectively.ConclusionsIn this largest-to-date randomized controlled trial in uremic pruritus, NAL 120 durably and significantly reduced the itching intensity among hemodialysis patients.© 2017 S. Karger AG, Basel.

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