Evidence map›Paper›PMID 37968132›Full record

Trial reportNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2024

Difelikefalin improves itch-related sleep disruption in patients undergoing haemodialysis.

Daniel E Weiner, Thilo Schaufler, Kieran McCafferty, Kamyar Kalantar-Zadeh, Michael Germain, Despina Ruessmann, Isabelle Morin, Frédérique Menzaghi, Warren Wen, Sonja Ständer

3 registry-linked trialsOpen access · hybridAbstract readRandomized Controlled TrialClinical Trial, Phase IIIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
5.4field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT03422653 phase3completednot on this map

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

TypeinterventionalSponsorCara Therapeutics, Inc.Ran2018 to 2020Enrolled378ConditionsUremic PruritusArmsCR845 0.5 mcg/kg, Placebo
NCT03636269 phase3completednot on this map

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

TypeinterventionalSponsorCara Therapeutics, Inc.Ran2018 to 2020Enrolled473ConditionsUremic PruritusArmsCR845 0.5 mcg/kg, Placebo
NCT03998163 phase3completednot on this map

An Open-Label, Multicenter Study to Evaluate the Safety and Effectiveness of Intravenous CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus

TypeinterventionalSponsorCara Therapeutics, Inc.Ran2019 to 2020Enrolled222ConditionsUremic PruritusArmsCR845 0.5 mcg/kg
3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Article
  6. Longitudinal Trajectories of CKD-Associated Pruritus.Kidney international reports · 2026
    Article
  7. Review
  8. Article
  9. Review
  10. Observational
  11. Article
  12. Article
  13. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 7 institutions in 4 countries.

Daniel E WeinerWilliam B. Schwartz MD Division of Nephrology, Tufts Medical Center, Boston, MA, USA.
Thilo SchauflerCSL Vifor, Glattbrugg, Switzerland.ORCID 0000-0003-1886-829X
Kieran McCaffertyThe Royal London Hospital-Barts Health NHS Trust, London, UK.
Kamyar Kalantar-ZadehDivision of Nephrology and Hypertension and Kidney Transplantation, University of California, Irvine, Irvine, CA, USA.ORCID 0000-0002-8666-0725
Michael GermainBaystate Medical Center, Springfield, MA, USA.ORCID 0000-0001-7481-2421
Despina RuessmannCSL Vifor, Glattbrugg, Switzerland.
Isabelle MorinCSL Vifor, Meyrin, Switzerland.
Frédérique MenzaghiCara Therapeutics, Stamford, CT, USA.
Warren WenCara Therapeutics, Stamford, CT, USA.
Sonja StänderCenter for Chronic Pruritus, Department of Dermatology, University Hospital Münster, Münster, Germany.
Vifor Pharma (Switzerland) · CHCara Therapeutics (United States) · USBarts Health NHS Trust · GBBaystate Medical Center · USTufts Medical Center · USUniversity Hospital Münster · DEUniversity of California, Irvine · US

Funding

Vifor Fresenius Medical Care Renal Pharma Ltd
6 · The paper itself

Abstract

backgroundPoor sleep quality is associated with higher mortality and lower quality of life in patients with chronic kidney disease-associated pruritus (CKD-aP). Difelikefalin reduces itch in patients with CKD-aP undergoing haemodialysis (HD). This post hoc analysis of the Phase 3 difelikefalin studies (Study 3105 and the pooled dataset from KALM-1 and KALM-2) evaluated whether itch reduction in individuals with CKD-aP improved sleep quality.

methodsItch intensity was assessed in patients undergoing HD who had moderate-to-severe CKD-aP treated with intravenous difelikefalin (0.5 µg/kg, three times weekly) (N = 222, Study 3105; N = 426, KALM-1 and -2) or placebo (N = 425, KALM-1 and -2) for 12 weeks, using the Worst Itch Intensity Numerical Rating Scale (WI-NRS). Sleep quality was assessed using the sleep disability question of the 5-D Itch Scale (5-D SDQ) in all studies and, in Study 3105, with the Sleep Quality Numeric Rating Scale (SQ-NRS).

resultsGreater improvements in sleep quality were observed in patients with ≥3-point versus <3-point WI-NRS improvement using SQ-NRS in Study 3105 [mean (95% confidence interval) -5.2 (-5.6, -4.8) vs -1.5 (-2.0, -1.0)] and 5-D SDQ in KALM-1 and -2 [-1.8 (-2.1, -1.6) vs -0.8 (-1.1, -0.4)]. SQ-NRS and WI-NRS scores were highly correlated at both baseline and Week 12 in Study 3105 (Spearman correlation coefficient: 0.77 and 0.84, respectively). Correlations were also observed between 5-D SDQ and WI-NRS scores in Study 3105 and KALM-1 and -2.

conclusionsIn patients undergoing HD with moderate-to-severe CKD-aP, itch reduction with intravenous difelikefalin was associated with improved sleep quality. As disturbed sleep may contribute to mortality and morbidity in CKD-aP, difelikefalin may help to address a major clinical burden by improving sleep quality, secondary to itch relief.

trial registrationKALM-1 (NCT03422653), KALM-2 (NCT03636269), Study 3105 (NCT03998163).

Indexed as

PruritusQuality of LifeRenal DialysisAgedDouble-Blind MethodFemaleFollow-Up StudiesHumansMaleMiddle AgedPiperidinesPrognosisRenal Insufficiency, ChronicSleep QualitySleep Wake DisordersdifelikefalinPiperidineschronic kidney disease–associated pruritusdifelikefalinhaemodialysisitchsleep

Identifiers

PMID37968132
PMCPMC11210984
OpenAlexW4388715822

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.