Difelikefalin for Itching in Hemodialysis Patients With Chronic Kidney Disease

Effect of Difelikefalin on CKD-Associated Pruritus in Patients on Maintenance Hemodialysis: A Randomized, Placebo-Controlled Trial

A randomized, placebo-controlled, double-blind trial will be conducted in the Department of Nephrology at Chittagong Medical College Hospital, Chattogram, Bangladesh, over a period of one and a half years. A total of 102 patients with chronic kidney disease (CKD) undergoing maintenance hemodialysis will be enrolled in the study.

Patients with moderate-to-severe pruritus, defined as a Worst Itching Intensity Numerical Rating Scale (WI-NRS) score ≥ 4, will be included. Eligible participants will be randomly assigned in a 1:1 ratio to receive either difelikefalin (0.5 mcg/kg) or placebo administered intravenously after each hemodialysis session for 6 weeks.

The primary outcome measure will be the change in WI-NRS score from baseline to week 6. Secondary outcomes will include changes in quality of life assessed using the Skindex-10 scale. Adverse events and safety parameters will also be monitored throughout the study period.

The primary analysis will be conducted using the intention-to-treat principle. A per-protocol analysis may also be performed as a secondary analysis. Statistical analysis will be carried out using SPSS version 27.

Study Overview

• Status: Not yet recruiting
• Conditions: CKD 5D, Hemodialysis; Itching Symptoms
• Intervention / Treatment: Drug: Difelikefalin Injection; Drug: Normal Saline (0.9% NaCl)

Detailed Description

Chronic kidney disease-associated pruritus (CKD-aP), alternatively termed uremic pruritus (UP), represents a frequent, distressing, and often incapacitating clinical manifestation among individuals diagnosed with chronic kidney disease (CKD) or end-stage renal disease (ESRD). Characterized by persistent, intense itching-typically generalized but occasionally localized-CKD-aP disproportionately affects patients undergoing hemodialysis, with epidemiological studies reporting a variable prevalence ranging from 22% to 84% in this population. Notably, a substantial subset of these patients, approximately 20-40%, experience moderate-to-severe pruritus, which significantly diminishes their quality of life.

The impact of CKD-aP extends beyond physical discomfort. The condition is associated with chronic sleep disturbances such as insomnia, fatigue, and dermatological complications including excoriations, lichenification, and secondary infections due to repeated scratching. Psychosocially, patients often experience emotional distress, social withdrawal, and stigmatization related to visible skin lesions, which may worsen underlying mental health conditions such as anxiety and depression. Additionally, CKD-aP has been associated with increased mortality in dialysis patients, including higher risks of cardiovascular events and infections, suggesting a link with systemic inflammation and immune dysregulation.

There is a clear need for effective treatment options for CKD-aP. Current off-label therapies include antihistamines, topical corticosteroids, gabapentin, and pregabalin. While some of these treatments may reduce itching, their side effects can limit their use in this population.

The pathogenesis of CKD-aP remains incompletely understood. Proposed mechanisms include metabolic disturbances, immune system dysregulation, and imbalance in the endogenous opioid system, particularly involving peripheral kappa opioid receptors.

Difelikefalin is a peripherally acting, selective kappa opioid receptor agonist that exerts antipruritic effects through activation of receptors on peripheral neurons and immune cells. Its hydrophilic peptide structure limits its ability to cross the blood-brain barrier, thereby reducing central nervous system effects.

Difelikefalin has been approved as the first medication specifically indicated for CKD-aP in patients undergoing dialysis and has demonstrated efficacy in phase 3 clinical trials. It is currently recommended as a first-line treatment for moderate-to-severe CKD-aP in dialysis patients where available.

Despite promising results, some limitations remain. A proportion of patients do not achieve clinically meaningful improvement in itch intensity or quality of life. Clinical trials have demonstrated significant benefits, but response variability persists.

The safety profile of difelikefalin is dose-dependent. Common adverse effects include nausea, vomiting, dizziness, diarrhea, and gait disturbances. A dose of 0.5 μg/kg appears to provide the most favorable balance between efficacy and safety.

Although difelikefalin is a promising treatment option, current evidence remains limited, and additional well-designed randomized controlled trials are needed to confirm its effectiveness.

While most existing studies have been conducted in Western populations, data from low- and middle-income countries such as Bangladesh are limited. The prevalence of CKD in Bangladesh is high, affecting millions of individuals, with a significant number progressing to end-stage renal disease annually.

This study aims to evaluate the superiority of difelikefalin over placebo in reducing pruritus severity among patients undergoing maintenance hemodialysis in a tertiary-level teaching hospital in Bangladesh.

• Study Type: Interventional
• Enrollment (Estimated): 106
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: MD SHARIFUL ISLAM SARKER, MBBS; Phone Number: +8801738647201 +8801521555223; Email: sobujshariful@gmail.com
• Study Contact Backup: Name: DR ZAKWAN ULLAH, MBBS; Phone Number: +8801680560222; Email: sharifulnephrology@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients aged ≥18 years
• Diagnosed with chronic kidney disease (CKD) on maintenance hemodialysis Undergoing hemodialysis for at least 3 months
• Presence of moderate-to-severe pruritus defined as Worst Itching Intensity Numerical Rating Scale (WI-NRS) score ≥4
• Able and willing to provide written informed consent

Exclusion Criteria:

• Known case of Primary skin disesease associated with Itching.
• Known case of liver disease.
• Known case of iron defeciency anaemia ,hematological malignancy.
• Known case of hypothyroidism & hyperthyroidism.
• Known case of allergic reaction to Opiates .
• Pregnancy.
• Drug abuse, or substance dependence

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Difelikefalin Group; Difelikefalin (0.5 mcg/kg) will be administered intravenously at the end of each hemodialysis session, three times per week, for a total duration of 6 weeks in patients with CKD-associated pruritus.	Drug: Difelikefalin Injection; ntravenous difelikefalin (κ-opioid receptor agonist) administered at a dose of 0.5 mcg/kg at the end of each hemodialysis session, three times weekly,for a total duration of 6 wks in patients undergoing maintenance hemodialysis with moderate to severe CKD -associated pruritus
Placebo Comparator: Placebo (Normal Saline) Group; Participants will receive intravenous normal saline at the end of each hemodialysis session, three times per week, for 6 weeks, administered in a volume equivalent to the difelikefalin dose	Drug: Normal Saline (0.9% NaCl); Intravenous normal saline will be administered at the end of each hemodialysis session, three times per week, for a total duration of 6 weeks, in a volume equivalent to the difelikefalin dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Worst Itching Intensity Numerical Rating Scale (WI-NRS) Score at 6 Weeks	The Worst Itching Intensity Numerical Rating Scale (WI-NRS) is an 11-point scale ranging from 0 (no itching) to 10 (worst imaginable itching). The outcome will be reported as the mean change in WI-NRS score from baseline to week 6	Baseline to Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Skindex-10 Score at 6 Weeks	Skindex-10 is a validated questionnaire used to assess quality of life in patients with skin conditions. Scores range from 0 to 60, with higher scores indicating worse quality of life. The outcome will be reported as the mean change from baseline to week 6.	Baseline to Week 6

Collaborators and Investigators

• Sponsor: Chittagong Medical College
• Investigators: Study Chair: PROF. DR. MD NURUL HUDA, FCPS,MD, Head of the department of nephrology,Chittagong medical college ,Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 26, 2026
• Primary Completion (Estimated): January 30, 2027
• Study Completion (Estimated): January 30, 2027

Study Registration Dates

• First Submitted: March 27, 2026
• First Submitted That Met QC Criteria: April 10, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pharmaceutical Preparations; Crystalloid Solutions; Isotonic Solutions; Solutions; Saline Solution; difelikefalin
• Other Study ID Numbers: 59.127.1557.013.19.PG.1238

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared due to privacy and confidentiality concerns, as well as institutional and ethical restrictions

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No