Efficacy and Safety of Nalfurafine Hydrochloride ODT for Moderate-to-Severe Pruritus in Patients on Peritoneal Dialysis

This is a multicenter, prospective, single-arm clinical study designed to evaluate the efficacy and safety of nalfurafine hydrochloride orally disintegrating tablets in treating moderate-to-severe pruritus in peritoneal dialysis patients. The study consists of three phases: a screening period (1-2 weeks), a treatment period (4 weeks), and a follow-up period (1 week). During the screening phase, baseline pruritus levels are established using the Visual Analog Scale (VAS) and the Shichuan-Kawashima Pruritus Severity Score. The treatment period begins with an initial dose of 2.5 μg/day, which may be adjusted to 5 μg/day after 2 weeks based on symptom response; the follow-up phase assesses pruritus improvement and safety. The study plans to enroll 93 patients (including a 20% dropout rate), with the primary endpoint being the change in VAS score from baseline to week 4 of treatment. Secondary endpoints include VAS score changes at different stages, quality-of-life improvements, and adverse event incidence.

Eligible patients are aged 18-85 years, undergoing regular peritoneal dialysis for ≥3 months, and meeting baseline VAS criteria for moderate-to-severe pruritus. The primary efficacy measure is the mean change in daily maximum VAS scores (baseline vs. week 4), while secondary measures include pruritus severity scores, sleep quality, dose adjustment rates, and laboratory safety data. Statistical analyses will follow intention-to-treat (ITT) and per-protocol (PP) principles. Based on preliminary data (mean 28.4 mm, standard deviation 21.82 mm), the sample size calculation ensures 95% power to validate efficacy hypotheses.

The intervention involves monotherapy with nalfurafine hydrochloride orally disintegrating tablets, starting at 2.5 μg/day, with a potential increase to 5 μg/day after 2 weeks. Standardized scales assess pruritus, quality of life, and sleep improvements, alongside monitoring of vital signs, electrocardiograms, and laboratory parameters for safety evaluation. Enrollment criteria require ≥5 days of recorded morning/evening VAS scores during the baseline period (average ≥50 mm) and ≥2 days with Shichuan-Kawashima pruritus scores ≥3 (moderate severity).

The study anticipates a significant reduction in VAS scores as the primary endpoint, with secondary endpoints including dose adjustments, safety events, and patient-reported outcomes. This single-arm self-controlled study validates drug efficacy while strictly controlling dropout rates and data integrity to ensure result reliability.

Inclusion criteria

At the time of signing informed consent:

• Aged 18-85 years (inclusive), regardless of gender.
• Chronic renal failure patients on regular peritoneal dialysis for ≥3 months, with no anticipated major treatment changes or rapid disease progression during the trial.
• Able to understand and comply with study procedures, voluntarily participate, and provide written informed consent.

At formal enrollment:

• During the baseline period, ≥5 days with both morning and evening VAS scores recorded, and the average of the higher VAS values (morning/evening) ≥50 mm.
• During the baseline period, ≥5 days with Xie-Kawashima itching severity assessed both morning and evening, including ≥2 days where the maximum itching score (morning/evening) was ≥3 (moderate).

Exclusion criteria

• Poor dialysis compliance, deemed by the investigator to affect efficacy/safety assessments.
• Poor dialysis compliance, deemed by the investigator to affect efficacy/safety assessments.
• Peritoneal dialysis regimen adjusted within 2 weeks prior to screening.
• Currently on or planning hemodialysis within 2 months.
• Planned kidney transplant or elective surgery during the study.
• Peritonitis within 4 weeks prior to screening, unable to continue peritoneal dialysis.
• ALT, AST, GGT, or total bilirubin >2× upper limit of normal (ULN) during screening.
• Pruritus not caused by chronic kidney disease (e.g., allergic, physical, infectious skin diseases, cholestatic liver disease).
• Severe cardiovascular disease (NYHA Class III/IV, acute MI, unstable angina, large pericardial effusion, severe arrhythmia, or ECG abnormalities deemed unsafe for participation).
• Active malignancy within 12 months prior to screening, or recent radiotherapy/chemotherapy/targeted/immunotherapy.
• Uncontrolled or drug-treated fungal/bacterial/viral infections (e.g., active TB, HIV).
• Uncontrolled hypertension (SBP ≥180 mmHg or DBP ≥110 mmHg).
• Current systemic corticosteroids/immunosuppressants (topical excluded).
• Psychiatric or cognitive disorders.
• Initiated/adjusted restricted medications (antihistamines, systemic/local corticosteroids [excluding ear/eye], calcineurin inhibitors, gabapentin, pregabalin) within 7 days prior to screening, or anticipated changes during the study.
• Initiated/adjusted medications affecting pruritus assessment (antipsychotics, hypnotics, SSRIs, anxiolytics, TCAs) within 2 weeks prior to screening, or anticipated changes during the study.
• Opioid agonists/antagonists used within 2 weeks prior to screening.
• Phototherapy for pruritus within 1 month prior to screening.
• History of drug abuse, dependence, or alcoholism within 12 months prior to screening.
• Allergy to opioids or trial drug excipients.
• Participation in another clinical trial with investigational drugs/devices within 28 days prior to screening, or residual investigational drug within 5 half-lives.
• Pregnant, breastfeeding, positive pregnancy test, or unwilling to use contraception during the study.
• Other conditions deemed unsuitable by the investigator.