Biomarker-Guided Mycophenolate Mofetil Elimination in Low-Risk Older Adult Kidney Transplant Recipients (OPTIMA-KT)
Optimizing Immunosuppression in Low-Risk Older Adult Kidney Transplant Recipients (OPTIMA-KT): A Prospective, Randomized, Open-Label, Blinded-Endpoint Single-Site Pilot/Feasibility Trial of Biomarker-Guided Mycophenolate Mofetil Elimination
Most kidney transplant recipients take a combination of anti-rejection medicines for the rest of their life. One of these is called mycophenolate mofetil (MMF), also known by the brand name CellCept. While MMF helps protect the kidney, taking it for many years can cause infections, low blood counts, stomach problems, and a higher risk of certain cancers, problems that older adults are especially likely to experience.
We are doing this study to learn whether carefully and slowly stopping MMF in older adults who are doing well after their transplant is as safe as continuing MMF, when we use blood and urine tests to closely watch for any early signs of trouble. The information learned could help future kidney transplant patients use less medicine without losing their transplant.
Studieoversikt
Status
Forhold
Detaljert beskrivelse
To evaluate the feasibility, safety, protocol adherence, biomarker monitoring completion, and preliminary clinical event rates associated with stepwise MMF elimination over 6 months compared with standard-of-care immunosuppression in low-risk older adult kidney transplant recipients.
Secondary objectives. To compare between arms: eGFR trajectory and proteinuria at Months 6 and 12; infection incidence (including CMV and BK), hospitalization, and adverse drug events; de novo DSA incidence and time to de novo DSA; and the kinetics and predictive performance of dd-cfDNA and urine CXCL9 and CXCL10 for rejection and de novo DSA.
Exploratory objectives. To assess the association between PIRCHE-II score and individual primary endpoint components; the performance of combined biomarker panels versus single biomarkers; health-related quality of life and patient-reported outcomes through Month 12; and cost and healthcare resource utilization through Month 12 across study arms.
Studietype
Registrering (Antatt)
Fase
- Tidlig fase 1
Kontakter og plasseringer
Studiekontakt
- Navn: Amber Paulus, PhD
- Telefonnummer: (804) 827-1743
- E-post: amber.paulus@vcuhealth.org
Studer Kontakt Backup
- Navn: Natalie Kilmarx
- Telefonnummer: (804) 828-7522
- E-post: natalie.salsini@vcuhealth.org
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Beskrivelse
Inclusion Criteria:
- Greater than 60 years of age
- Greater than 12 months from kidney transplant
- Stable maintenance tacrolimus- based immunosuppression for at least 3 months without dose changes greater than 25%
- PIRCHE-II score less than or equal to 65 calculated from available donor and recipient HLA typing
- Ability to provide written informed consent and comply with study procedures
Exclusion Criteria:
- Multi-organ transplant or prior graft loss due to rejection
- Maintenance immunosuppression including belatacept, cyclosporine, azathioprine, sirolimus, or other agents in lieu of tacrolimus or MMF
- Steroid-free regimen
- Active malignancy (excluding non-melanoma skin cancer)
- Uncontrolled infection
- BK viremia greater than 10,000 copies/mL, or BK nephropathy
- High immunologic risk (any preformed DSA, positive crossmatch, or biopsy-proven rejection within the prior 6 months)
- Pregnancy, breastfeeding, self-reported pregnancy, positive pregnancy test during screening if testing is indicated, or inability/unwillingness to comply with required pregnancy prevention measures if of childbearing potential
- Inability to comply with study procedures including monthly visits and biospecimen collection
- Concurrent participation in another conflicting interventional trial.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Aktiv komparator: Standard of Care
Participants continue tacrolimus-based maintenance immunosuppression (tacrolimus, MMF, with or without prednisone)
|
Administration of Tacrolimus
Participants are administered MMF
Participants in SOC arm may be administered Prednisone as indicated
|
|
Eksperimentell: MMF Elimination (Mycophenolate Mofetil )
Mycophenolate Mofetil (MMF) is reduced to approximately 50% of baseline daily dose at Month 1, approximately 25% at Month 2, and discontinued at Month 3, remaining discontinued through Month 6 unless biomarker triggers prompt reinstatement.
Tacrolimus trough is maintained at 5 to 8 ng/mL with monthly monitoring and coefficient of variation tracking; prednisone is continued at site-standard dose unless contraindicated.
|
Administration of Tacrolimus
Participants are administered MMF
Participants in the MMF Elimination arm may be administered prednisone as indicated
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Feasibility of MMF Elimination
Tidsramme: 6 months
|
Proportion of eligible participants enrolled and retained through completion of the intervention
|
6 months
|
|
Protocol Adherence
Tidsramme: 6 months
|
Proportion of participants completing the assigned treatment strategy without major protocol deviations
|
6 months
|
|
Biomarker Monitoring Completion
Tidsramme: 6 months
|
Proportion of scheduled biomarker assessments successfully completed.
|
6 months
|
|
Clinical Composite Event Rate
Tidsramme: 6 months
|
Time to first occurrence of all-cause death, graft loss, biopsy-proven rejection, major infection requiring IV therapy or hospitalization, graft-related hospitalization, or confirmed de novo donor-specific antibody.
|
6 months
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Compare estimated glomerular filtration rate (eGFR) trajectory at Months 6 and 12
Tidsramme: Months 6 and 12
|
Compare estimated glomerular filtration rate (eGFR) trajectory at Months 6 and 12.
|
Months 6 and 12
|
|
Compare Urine Protein-to-Creatinine Ratio (UPCR) Between Arms at Months 6 and 12
Tidsramme: Months 6 and 12
|
Compare Urine Protein-to-Creatinine Ratio (UPCR) Between Arms at Months 6 and 12.
|
Months 6 and 12
|
|
Comparison of Infection incidence
Tidsramme: Months 6 and 12
|
Number of participants experiencing one or more infections
|
Months 6 and 12
|
|
Comparison of Participants Hospitalized
Tidsramme: Months 6 and 12
|
Number of participants experiencing one or more hospitalizations
|
Months 6 and 12
|
|
Comparison of Total Hospitalizations
Tidsramme: Months 6 and 12
|
Total number of hospitalizations across all participants
|
Months 6 and 12
|
|
Comparison of adverse events
Tidsramme: Months 6 and 12
|
Number of participants experiencing one or more adverse events
|
Months 6 and 12
|
|
Comparison of serious adverse events
Tidsramme: Months 6 and 12
|
Number of participants experiencing one or more serious adverse events
|
Months 6 and 12
|
|
De Novo Donor-Specific Antibody Incidence
Tidsramme: Month 12
|
Number of participants who develop confirmed de novo donor-specific antibodies after randomization
|
Month 12
|
|
Time to De Novo Donor-Specific Antibody
Tidsramme: Month12
|
Time from randomization to first confirmed de novo donor-specific antibody
|
Month12
|
|
Donor-Derived Cell-Free DNA (dd-cfDNA)
Tidsramme: Month 12
|
Longitudinal change in dd-cfDNA and its predictive performance for rejection and de novo donor-specific antibody
|
Month 12
|
|
Urine CXCL9 Concentration (pg/mL)
Tidsramme: Month 12
|
Longitudinal change in urine CXCL9 and its predictive performance for rejection and de novo donor-specific antibody
|
Month 12
|
|
Urine CXCL10 Concentration (pg/mL)
Tidsramme: Month 12
|
Longitudinal change in urine CXCL10 and its predictive performance for rejection and de novo donor-specific antibody
|
Month 12
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Amber Paulus, PhD, Virginia Commonwealth University
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
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- HM300000943
Plan for individuelle deltakerdata (IPD)
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IPD-planbeskrivelse
IPD-delingstidsramme
Tilgangskriterier for IPD-deling
IPD-deling Støtteinformasjonstype
- STUDY_PROTOCOL
- ICF
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