Effect of Difelikefalin on CKD-Associated Pruritus in Patients on Maintenance Hemodialysis: A Randomized, Placebo-Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 106
- 主要终点
- Change From Baseline in Worst Itching Intensity Numerical Rating Scale (WI-NRS) Score at 6 Weeks
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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
干预措施: Normal Saline (0.9% NaCl) (Drug)
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.
干预措施: Difelikefalin Injection (Drug)
结局指标
主要结局
Change From Baseline in Worst Itching Intensity Numerical Rating Scale (WI-NRS) Score at 6 Weeks
时间窗: Baseline to Week 6
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
次要结局
- Change From Baseline in Skindex-10 Score at 6 Weeks(Baseline to Week 6)
研究者
DR.MD.SHARIFUL ISLAM SARKER
Resident
Chittagong Medical College