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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Mohamed Mamdouh Elsayed, MD
- Phone Number: +201068055103
- Email: dr_mohamedmamdouh87@yahoo.com
Study Locations
-
-
Egypt
-
Alexandria, Egypt, Egypt, 21526
- Faculty of Medicine, Aexandria University
-
Contact:
- Mohamed Mamdouh Elsayed, MD
- Phone Number: +201068055103
- Email: dr_mohamedmamdouh87@yahoo.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
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 |
|
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 |
|
Placebo Comparator: placebo
Patients will receive a matched placebo for the 12-week duration. |
Patients will receive a matched placebo for the 12-week duration |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in Uremic Pruritus Intensity
Time Frame: 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
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Percentage of Participants Achieving a Clinically Significant Reduction in Pruritus Severity
Time Frame: 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)
Time Frame: 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
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Mohamed Mamdouh Elsayed, MD, University of Alexandria
- Study Chair: Mohamed A Abdelhalim, MD, Medical Research Institute, Alexandria University
Publications and helpful links
General Publications
- 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.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- mirogabalin & uremic pruritis
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.