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Randomized Controlled Trial of Difelikefalin for Chronic Pruritus in Hemodialysis Patients

2020; Elsevier BV; Volume: 5; Issue: 5 Linguagem: Inglês

10.1016/j.ekir.2020.01.006

2468-0249

Steven Fishbane, Vandana Mathur, Michael J. Germain, Shayan Shirazian, Sarbani Bhaduri, Catherine Munera, Robert H. Spencer, Frédérique Menzaghi, Michael J. Aaronson, Kelly Alford, Ahmed Awad, Premila Bhat, V. Broumand, Wesley Calhoun, Riad Darwish, Sohan Dua, Carl Dukes, Ayodele Erinle, A Hadley, John Hsieh, Mohammad Kashif, Nelson Kopyt, Kumar Jayant, Jorge Kusnir, Jean Lee, Essam Maasarani, Richard J. Miller, M. Reza Mizani, Jesús Navarro, Amber S. Podoll, Thomas Pohlman, Denise Rivers, Derrick Robinson, Lisa Rich, Shayan Shirazian, Arnold Silva, Mark Caleb Smith, Joel Michels Topf, James A. Tumlin, Scott Ungar, Steven Zeig,

Pain Mechanisms and Treatments

There is an unmet medical need for pruritus associated with chronic kidney disease, a distressing complication characterized by generalized and persistent itch affecting 20% to 40% of patients undergoing hemodialysis. Here we report the results of a phase 2 trial evaluating the efficacy and safety of a novel peripherally restricted kappa opioid receptor agonist, difelikefalin, in adult patients undergoing hemodialysis with pruritus.In this study, 174 hemodialysis patients with moderate-to-severe pruritus were randomly assigned to receive difelikefalin (0.5, 1.0, or 1.5 μg/kg) or placebo intravenously thrice weekly after each hemodialysis session for 8 weeks in a double-blind, controlled trial. The primary endpoint was the change from baseline at week 8 in the weekly mean of the 24-hour Worst Itching Intensity Numerical Rating Scale score. The secondary efficacy endpoint was the change in itch-related quality of life measured by the Skindex-10 questionnaire. Other endpoints included safety, sleep quality, and additional measures including the 5-D itch scale.A significant reduction from baseline in itch intensity scores at week 8 favored all difelikefalin doses combined versus placebo (P = 0.002). Difelikefalin also showed improvement over placebo in Skindex-10, 5-D itch, and sleep disturbance scores (P ≤ 0.005). Overall, 78% of patients receiving difelikefalin reported treatment-emergent adverse events versus 42% of patients given placebo, with diarrhea, dizziness, nausea, somnolence, and fall being the most frequent (≥5%).In this trial, difelikefalin effectively reduced itching intensity and improved sleep and itch-related quality of life.