Trial reportThe New England journal of medicine2020
A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus.
Trial report in The New England journal of medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03422653 (A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Intravenous CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus, With a 52-Week Open Label Extension), which is not on this map. Cited by 179 papers, 8 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Intravenous CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus, With a 52-Week Open Label Extension
Who cites it
179 citing papers in PubMed, 8 syntheses or guidelines pooled it.
- Prevalence and associated factors of chronic kidney disease-associated pruritus in maintenance hemodialysis patients: a systematic review and meta-analysis.BMC nephrology · 2026Pooled it
- Real-world effectiveness and safety of difelikefalin for chronic kidney disease-associated pruritus: a systematic review.Renal failure · 2026Pooled it
- European S2k Guideline on Chronic PruritusActa dermato-venereologica · 2025Guideline
- Chronic kidney disease-associated pruritus and patient-centred outcomes: a systematic review.Journal of nephrology · 2025Pooled it
- The efficacy and safety of difelikefalin for pruritus in hemodialysis patients: a systematic review and meta-analysis of randomized controlled trials.Renal failure · 2024Pooled it
- Difelikefalin in the treatment of hemodialysis patients with pruritus: a systematic review and meta-analysis.Frontiers in pharmacology · 2024Pooled it
- Pharmacological interventions for pruritus in adult palliative care patients.The Cochrane database of systematic reviews · 2023Pooled it
- The effect of hyperkalemia and long inter-dialytic interval on morbidity and mortality in patients receiving hemodialysis: a systematic review.Renal failure · 2021Pooled it
- Influence of Concomitant Opioids on Difelikefalin Treatment Outcomes in Adults with Moderate-to-Severe Pruritus on Maintenance Hemodialysis: Exploratory Analyses.Kidney & blood pressure research · 2026Trial
- Psychometric validation and meaningful change thresholds of the Skindex-10 questionnaire and 5-D Itch scale for assessing itch in patients with chronic kidney disease-associated pruritus.Journal of patient-reported outcomes · 2025Trial
- Efficacy and safety of anrikefon in patients with pruritus undergoing haemodialysis: multicentre, double blind, randomised placebo controlled phase 3 trial.BMJ (Clinical research ed.) · 2025Trial
- Influence of Baseline Itch Severity on Treatment Outcomes With Difelikefalin in Adults With Moderate-to-Severe Pruritus Receiving Maintenance Haemodialysis: An Exploratory Analysis.Journal of renal care · 2025Trial
- HSK21542 in patients with postoperative pain: two phase 3, multicentre, double-blind, randomized, controlled trials.Nature communications · 2025Trial
- Impact of renal impairment on the pharmacokinetic profile of intravenous difelikefalin, a kappa opioid receptor agonist for the treatment of pruritus.BMC nephrology · 2024Trial
- Difelikefalin improves itch-related sleep disruption in patients undergoing haemodialysis.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Trial
- Trial
- Difelikefalin in Black/African American Hemodialysis Patients with Moderate-to-Severe Pruritus: Post hoc Analysis of KALM-1 and KALM-2.American journal of nephrology · 2024Trial
- Randomized controlled trial of nalfurafine for refractory pruritus in hemodialysis patients.Renal failure · 2023Trial
- Assessment of the physical dependence potential of difelikefalin: Randomized placebo-controlled study in patients receiving hemodialysis.Clinical and translational science · 2023Trial
- Narrowband-ultraviolet B vs Broadband-ultraviolet B in Treatment of Chronic Pruritus: A Randomized, Single-blinded, Non-inferiority Study.Acta dermato-venereologica · 2023Trial
119 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDifelikefalin is a peripherally restricted and selective agonist of kappa opioid receptors that are considered to be important in modulating pruritus in conditions such as chronic kidney disease.
methodsIn this double-blind, placebo-controlled, phase 3 trial, we randomly assigned patients undergoing hemodialysis who had moderate-to-severe pruritus to receive either intravenous difelikefalin (at a dose of 0.5 μg per kilogram of body weight) or placebo three times per week for 12 weeks. The primary outcome was the percentage of patients with an improvement (decrease) of at least 3 points from baseline at week 12 in the weekly mean score on the 24-hour Worst Itching Intensity Numerical Rating Scale (WI-NRS; scores range from 0 to 10, with higher scores indicating greater itch intensity). The secondary outcomes included the change from baseline in itch-related quality-of-life measures, the percentage of patients with an improvement of at least 4 points in the WI-NRS score at week 12, and safety.
resultsA total of 378 patients underwent randomization. A total of 82 of 158 patients (51.9%) in the difelikefalin group had a decrease of at least 3 points in the WI-NRS score (primary outcome), as compared with 51 of 165 (30.9%) in the placebo group. The imputed percentage of patients with a decrease of at least 3 points in the WI-NRS score was 49.1% in the difelikefalin group, as compared with 27.9% in the placebo group (P<0.001). Difelikefalin also resulted in a significant improvement from baseline to week 12 in itch-related quality of life as measured by the 5-D itch scale and the Skindex-10 scale. The imputed percentage of patients with a decrease of at least 4 points in the WI-NRS score at week 12 was significantly greater in the difelikefalin group than in the placebo group (37.1% [observed data: 64 of 158 patients] vs. 17.9% [observed data: 35 of 165 patients], P<0.001). Diarrhea, dizziness, and vomiting were more common in the difelikefalin group than in the placebo group.
conclusionsPatients treated with difelikefalin had a significant reduction in itch intensity and improved itch-related quality of life as compared with those who received placebo. (Funded by Cara Therapeutics; KALM-1 ClinicalTrials.gov number, NCT03422653.).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.