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.
調査の概要
状態
条件
詳細な説明
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.
研究の種類
入学 (推定)
段階
- 初期フェーズ 1
連絡先と場所
研究連絡先
- 名前：Amber Paulus, PhD
- 電話番号：(804) 827-1743
- メール：amber.paulus@vcuhealth.org
研究連絡先のバックアップ
- 名前：Natalie Kilmarx
- 電話番号：(804) 828-7522
- メール：natalie.salsini@vcuhealth.org
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
アクティブコンパレータ：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
|
|
実験的：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
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Feasibility of MMF Elimination
時間枠：6 months
|
Proportion of eligible participants enrolled and retained through completion of the intervention
|
6 months
|
|
Protocol Adherence
時間枠：6 months
|
Proportion of participants completing the assigned treatment strategy without major protocol deviations
|
6 months
|
|
Biomarker Monitoring Completion
時間枠：6 months
|
Proportion of scheduled biomarker assessments successfully completed.
|
6 months
|
|
Clinical Composite Event Rate
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Compare estimated glomerular filtration rate (eGFR) trajectory at Months 6 and 12
時間枠：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
時間枠：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
時間枠：Months 6 and 12
|
Number of participants experiencing one or more infections
|
Months 6 and 12
|
|
Comparison of Participants Hospitalized
時間枠：Months 6 and 12
|
Number of participants experiencing one or more hospitalizations
|
Months 6 and 12
|
|
Comparison of Total Hospitalizations
時間枠：Months 6 and 12
|
Total number of hospitalizations across all participants
|
Months 6 and 12
|
|
Comparison of adverse events
時間枠：Months 6 and 12
|
Number of participants experiencing one or more adverse events
|
Months 6 and 12
|
|
Comparison of serious adverse events
時間枠：Months 6 and 12
|
Number of participants experiencing one or more serious adverse events
|
Months 6 and 12
|
|
De Novo Donor-Specific Antibody Incidence
時間枠：Month 12
|
Number of participants who develop confirmed de novo donor-specific antibodies after randomization
|
Month 12
|
|
Time to De Novo Donor-Specific Antibody
時間枠：Month12
|
Time from randomization to first confirmed de novo donor-specific antibody
|
Month12
|
|
Donor-Derived Cell-Free DNA (dd-cfDNA)
時間枠：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)
時間枠：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)
時間枠：Month 12
|
Longitudinal change in urine CXCL10 and its predictive performance for rejection and de novo donor-specific antibody
|
Month 12
|
協力者と研究者
捜査官
- 主任研究者：Amber Paulus, PhD、Virginia Commonwealth University
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- HM300000943
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
IPD 共有時間枠
IPD 共有アクセス基準
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- ICF
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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