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.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Inscription (Estimé)
Phase
- Phase 2
Contacts et emplacements
Coordonnées de l'étude
- Nom: Mohamed Mamdouh Elsayed, MD
- Numéro de téléphone: +201068055103
- E-mail: dr_mohamedmamdouh87@yahoo.com
Lieux d'étude
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-
Egypt
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Alexandria, Egypt, Egypte, 21526
- Faculty of Medicine, Aexandria University
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Contact:
- Mohamed Mamdouh Elsayed, MD
- Numéro de téléphone: +201068055103
- E-mail: dr_mohamedmamdouh87@yahoo.com
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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 d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Tripler
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: 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 |
|
Expérimental: 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 |
|
Comparateur placebo: placebo
Patients will receive a matched placebo for the 12-week duration. |
Patients will receive a matched placebo for the 12-week duration |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Change in Uremic Pruritus Intensity
Délai: Baseline to Week 12
|
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
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Percentage of Participants Achieving a Clinically Significant Reduction in Pruritus Severity
Délai: Baseline and Week 12
|
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
|
|
Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs)
Délai: Up to Week 12
|
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
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Mohamed Mamdouh Elsayed, MD, University of Alexandria
- Chaise d'étude: Mohamed A Abdelhalim, MD, Medical Research Institute, Alexandria University
Publications et liens utiles
Publications générales
- 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.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- mirogabalin & uremic pruritis
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Informations sur les médicaments et les dispositifs, documents d'étude
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