Efficacy and Safety of Mirogabalin in Uremic Pruritus
Efficacy and Safety of Mirogabalin for Uremic Pruritus in Hemodialysis Patients: A Randomized Controlled Trial
This study aims to assess the efficacy and safety of mirogabalin in alleviating moderate-to-severe uremic pruritus in patients undergoing maintenance hemodialysis, and to establish the optimal dosing frequency by comparing continuous daily administration against intermittent post-dialysis administration.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Uremic pruritus is a prevalent and distressing condition affecting over 60% of patients undergoing hemodialysis, with 20% to 40% experiencing moderate-to-severe symptoms. This condition is strongly associated with poor sleep architecture, depression, diminished quality of life, and an increased risk of mortality. The exact pathogenesis is multifactorial, involving metabolic disturbances, dysregulated immune responses, imbalances in the endogenous opioid system, and peripheral neuropathy.
While current off-label therapies for uremic pruritus include gabapentinoids targeting neuropathic mechanisms, their clinical utility in end-stage renal disease (ESRD) is severely limited by dose-dependent central nervous system (CNS) toxicity, particularly somnolence and dizziness. Mirogabalin is a novel, preferentially selective α2δ - 1 ligand hypothesized to provide robust anti-pruritic efficacy with a significantly lower incidence of neurotoxicity. Because mirogabalin is primarily eliminated by the kidneys, this trial will evaluate the efficacy, safety, and optimal dosing frequency (daily versus post-dialysis intermittent dosing) to prevent drug accumulation in the hemodialysis population.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Mohamed Mamdouh Elsayed, MD
- Número de teléfono: +201068055103
- Correo electrónico: dr_mohamedmamdouh87@yahoo.com
Ubicaciones de estudio
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Egypt
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Alexandria, Egypt, Egipto, 21526
- Faculty of Medicine, Aexandria University
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Contacto:
- Mohamed Mamdouh Elsayed, MD
- Número de teléfono: +201068055103
- Correo electrónico: dr_mohamedmamdouh87@yahoo.com
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- ≥1 month of maintenance haemodialysis, 3 times per week for 4 hours.
- Adult patients with ages between 18-80 years.
- Patients presenting with moderate-to-severe pruritus, confirmed during the 7-day run-in period.
Exclusion Criteria:
- Primary skin diseases (eczema, psoriasis, allergic dermatitis or drug rash).
- History of Peripheral neuropathy, thyroid disease, leukemia, lymphoma, liver disease, Systemic lupus erythematosus or current pregnancy.
- Patients who consumed emollients cream, antihistamine, opioid antagonist, immunosuppressants, cholestyramine, corticosteroids or UVB phototherapy 1 month before study.
- Severe uncontrolled metabolic derangements defined as a calcium X phosphorus (Ca X P) >55.0 mg/dl, P >5.5 mg/dl, parathyroid hormone (PTH) >450 pg/ml.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Triple
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Mirogabalin (Intermittent)
Patients will receive mirogabalin 5 mg three times per week, administered immediately after each hemodialysis session for the 12-week duration. |
Patients will receive mirogabalin 5 mg three times per week, administered immediately after each hemodialysis session for the 12-week duration |
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Experimental: Mirogabalin (Daily)
Patients will receive mirogabalin 5 mg once daily for the 12-week duration. |
Patients will receive mirogabalin 5 mg once daily for the 12-week duration |
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Comparador de placebos: placebo
Patients will receive a matched placebo for the 12-week duration. |
Patients will receive a matched placebo for the 12-week duration |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change in Uremic Pruritus Intensity
Periodo de tiempo: Baseline to Week 12
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The mean change in uremic pruritus intensity will be measured by two tools: the Visual Analogue Scale (VAS) and the 5-D itch scale. The VAS ranges from 0 (no pruritus) to 10 (worst possible itching). The 5-D itch scale ranges from 5 to 25, with higher scores reflecting worse pruritus severity. |
Baseline to Week 12
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Percentage of Participants Achieving a Clinically Significant Reduction in Pruritus Severity
Periodo de tiempo: Baseline and Week 12
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Pruritus severity will be assessed using the Visual Analogue Scale (VAS), which ranges from 0 (no pruritus) to 10 (worst possible itching). A clinically significant reduction is defined as a shift in severity grade, such as moving from severe/very severe ($\ge 7$) to mild/moderate (<7). |
Baseline and Week 12
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Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs)
Periodo de tiempo: Up to Week 12
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Safety and tolerability will be evaluated and compared between the intermittent and daily mirogabalin arms. This measure will track the number of participants experiencing central nervous system adverse events (e.g., dizziness, somnolence, confusion) and gastrointestinal events (e.g., diarrhea, vomiting), along with the clinical grading of their severity. |
Up to Week 12
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Mohamed Mamdouh Elsayed, MD, University of Alexandria
- Silla de estudio: Mohamed A Abdelhalim, MD, Medical Research Institute, Alexandria University
Publicaciones y enlaces útiles
Publicaciones Generales
- Rayner HC, Larkina M, Wang M, Graham-Brown M, van der Veer SN, Ecder T, Hasegawa T, Kleophas W, Bieber BA, Tentori F, Robinson BM, Pisoni RL. International Comparisons of Prevalence, Awareness, and Treatment of Pruritus in People on Hemodialysis. Clin J Am Soc Nephrol. 2017 Dec 7;12(12):2000-2007. doi: 10.2215/CJN.03280317. Epub 2017 Sep 18.
- Deeks ED. Mirogabalin: First Global Approval. Drugs. 2019 Mar;79(4):463-468. doi: 10.1007/s40265-019-01070-8.
- Fishbane S, Jamal A, Munera C, Wen W, Menzaghi F; KALM-1 Trial Investigators. A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus. N Engl J Med. 2020 Jan 16;382(3):222-232. doi: 10.1056/NEJMoa1912770. Epub 2019 Nov 8.
- Elsayed MM, Elgohary IE, Abdelhamid HHS, Zaki SA. The effectiveness of sertraline in alleviating uremic pruritus in hemodialysis patients: a randomized clinical trial. BMC Nephrol. 2023 Jun 3;24(1):155. doi: 10.1186/s12882-023-03212-3.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- mirogabalin & uremic pruritis
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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