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.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Registrering (Antatt)
Fase
- Fase 2
Kontakter og plasseringer
Studiekontakt
- Navn: Mohamed Mamdouh Elsayed, MD
- Telefonnummer: +201068055103
- E-post: dr_mohamedmamdouh87@yahoo.com
Studiesteder
-
-
Egypt
-
Alexandria, Egypt, Egypt, 21526
- Faculty of Medicine, Aexandria University
-
Ta kontakt med:
- Mohamed Mamdouh Elsayed, MD
- Telefonnummer: +201068055103
- E-post: dr_mohamedmamdouh87@yahoo.com
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Trippel
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 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 |
|
Eksperimentell: 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 komparator: placebo
Patients will receive a matched placebo for the 12-week duration. |
Patients will receive a matched placebo for the 12-week duration |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Change in Uremic Pruritus Intensity
Tidsramme: 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
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Percentage of Participants Achieving a Clinically Significant Reduction in Pruritus Severity
Tidsramme: 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)
Tidsramme: 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
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Mohamed Mamdouh Elsayed, MD, University of Alexandria
- Studiestol: Mohamed A Abdelhalim, MD, Medical Research Institute, Alexandria University
Publikasjoner og nyttige lenker
Generelle publikasjoner
- 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.
Studierekorddatoer
Studer hoveddatoer
Studiestart (Antatt)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- mirogabalin & uremic pruritis
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .