Trial reportClinical and translational science2021
Effect of difelikefalin, a selective kappa opioid receptor agonist, on respiratory depression: A randomized, double-blind, placebo-controlled trial.
Trial report in Clinical and translational science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 32 citations in OpenAlex.
- 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
- 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
- Safety, tolerability, pharmacokinetics, and pharmacodynamics of a novel kappa opioid receptor agonist ZYKR1: a randomized double-blind placebo-control phase 1 study in healthy adult human participants.Naunyn-Schmiedeberg's archives of pharmacology · 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
- Assessment of the physical dependence potential of difelikefalin: Randomized placebo-controlled study in patients receiving hemodialysis.Clinical and translational science · 2023Trial
- Evaluation of the abuse potential of difelikefalin, a selective kappa-opioid receptor agonist, in recreational polydrug users.Clinical and translational science · 2022Trial
- Progress in peptide and protein therapeutics: Challenges and strategies.Acta pharmaceutica Sinica. B · 2025Review
- The efficacy and safety of kappa opioid receptor (KOR) agonists in patients with uraemic pruritus: a systematic review and network meta-analysis.Clinical kidney journal · 2025Article
- Morphine-Induced Antinociception Is Potentiated and Dopamine Elevations Are Inhibited by the Biased Kappa Opioid Receptor Agonist Triazole 1.1.ACS chemical neuroscience · 2025Article
- Effects of Biased Analogues of the Kappa Opioid Receptor Agonist, U50,488, in Preclinical Models of Pain and Side Effects.Molecules (Basel, Switzerland) · 2025Article
- Serotonin therapies for opioid-induced disordered swallow and respiratory depression.Journal of applied physiology (Bethesda, Md. : 1985) · 2024Article
- Pharmacokinetics, Metabolism, and Excretion of Intravenous [14C]Difelikefalin in Healthy Subjects and Subjects on Hemodialysis.Clinical pharmacokinetics · 2023Article
- The Kappa Opioid Receptor Agonist 16-Bromo Salvinorin A Has Anti-Cocaine Effects without Significant Effects on Locomotion, Food Reward, Learning and Memory, or Anxiety and Depressive-like Behaviors.Molecules (Basel, Switzerland) · 2023Article
- Safety and effectiveness of HSK21542 for hemodialysis patients: a multiple ascending dose study.Frontiers in pharmacology · 2023Article
- Difelikefalin in the Treatment of Chronic Kidney Disease-Associated Pruritus: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Anatomical Analysis of Transient Potential Vanilloid Receptor 1 (Frontiers in molecular neuroscience · 2022Article
- The Kappa Opioid Receptor: A Promising Therapeutic Target for Multiple Pathologies.Frontiers in pharmacology · 2022Review
- Difelikefalin: First Approval.Drugs · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Difelikefalin, a selective kappa opioid receptor agonist designed to limit central nervous system (CNS) penetration, is under development for the treatment of pruritus. Its hydrophilic, small-peptidic structure limits CNS entry, minimizing potential CNS-mediated adverse events (AEs). This study assessed the effect of difelikefalin on key relevant measures of respiratory depression in healthy volunteers. This single-center, randomized, double-blind, placebo-controlled, three-way crossover study enrolled healthy, nonsmoking volunteers. Subjects were randomized to 1 of 3 treatment sequences of difelikefalin (1.0 or 5.0 mcg/kg i.v.) or placebo on sequential days with an intervening 24 (±2) h washout period. The primary end points included incidence of increased end-tidal carbon dioxide (ETCO
Indexed as
Identifiers
What OpenQuestion holds
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.