Safety and Effectiveness of Difelikefalin in Patients With Moderate-to-Severe Pruritus Undergoing Hemodialysis: An Open-Label, Multicenter Study.
Kidney Med
; 4(10): 100542, 2022 Oct.
Article
de En
| MEDLINE
| ID: mdl-36185706
ABSTRACT
Rationale & Objective:
Individuals with chronic kidney disease frequently suffer from chronic kidney disease-associated pruritus (CKD-aP), impacting sleep quality and quality of life (QoL) and increasing the likelihood of depression. Difelikefalin is a kappa-opioid receptor agonist recently approved in the United States for the treatment of moderate-to-severe CKD-aP in hemodialysis patients. Study 3105 was conducted to further assess the safety of difelikefalin and the effects on pruritus and QoL. StudyDesign:
Open-label, multicenter, single-arm intervention trial. Setting &Participants:
Maintenance hemodialysis patients with moderate-to-severe CKD-aP at enrollment. Intervention Intravenous difelikefalin 0.5 µg/kg after each hemodialysis session for 12 weeks.Outcomes:
The primary outcome was safety of difelikefalin. Secondary outcomes included effectiveness of reducing itch intensity, assessed by the Worst Itching Intensity Numerical Rating Scale (WI-NRS); improving itch-related QoL, assessed with 5-D itch and Skindex-10 scales; and improvement of sleep, assessed with the Sleep Quality Numerial Rating Scale. Clinically meaningful thresholds for improvement in itch and QoL were previously established in this population.Results:
Among 222 participants with baseline WI-NRS ≥5, mean [standard deviation] WI-NRS was 7.6 [1.3], mean age 58 years, 55% were male, and mean dialysis duration was 5.9 years; 197 participants (89%) completed treatment. Treatment-related treatment-emergent adverse events were reported in 16 participants (7.2%); those most commonly reported were somnolence (1.8%), hypoesthesia (1.4%), nausea (0.9%), and dizziness (0.9%). No deaths or serious treatment-emergent adverse events were considered treatment-related. Clinically meaningful reduction in itch intensity (≥3-point improvement) was reported by 74% of participants, with 70% and 63% also reporting a clinically relevant improvement in QoL as measured by 5-D itch and Skindex-10. Sleep quality improvement (≥3-point reduction on the Numerical Rating Scale) was reported in 66% of participants.Limitations:
No placebo control group.Conclusions:
Difelikefalin was well tolerated, and treatment was associated with clinically meaningful improvements in itch intensity and itch-related QoL measures as well as improvements in sleep quality among individuals receiving hemodialysis who had moderate-to-severe CKD-aP, providing important insights into expected real-world effectiveness.Funding:
Cara Therapeutics. Trial Registration NCT03998163.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Type d'étude:
Clinical_trials
Aspects:
Patient_preference
Langue:
En
Journal:
Kidney Med
Année:
2022
Type de document:
Article