Kidney Immunosuppression Dosed Daily Only (KIDDO) - A Pilot Study
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Adherence to medical therapies and medications: as assessed by Medication Event Monitoring System (MEMS) at Day 210
研究概览
简要总结
Medication non-adherence is a major risk factor for graft dysfunction and graft loss among pediatric and adult transplant recipients. Rates of non-adherence in these populations are estimated between 30 and 70%, with the highest prevalence in adolescent and young adult (AYA) transplant recipients. Treatment-related factors known to impact rates of adherence include the number of medication doses per day and the number of tablets or capsules a patient takes per day, or "pill burden". One approach to minimizing dosing frequency and pill-burden includes transitioning patients to once-daily formulations. The current literature investigating utilization of once-daily immunosuppressive regimens in the AYA kidney transplant population is limited.
详细描述
One approach to minimizing dosing frequency and pill-burden includes transitioning patients to once-daily formulations.3 The current literature investigating utilization of once-daily immunosuppressive regimens in the AYA kidney transplant population is limited. Two studies have demonstrated safe and effective conversion of twice-daily tacrolimus to the Astagraf® in stable pediatric solid organ transplant recipients.4,5 Patients maintained equivalent tacrolimus exposure and experienced similar rates of rejection and graft loss in the first year post-conversion.5 To date, experience with another once-daily extended release (XR) tacrolimus product, Envarsus XR®, has not been published in the AYA population. Additionally, adherence studies evaluating a once-daily immunosuppression regimen including extended-release tacrolimus and azathioprine (which is dosed once daily as opposed to the twice daily dosing required for azathioprine's alternative mycophenolate mofetil) have not been conducted.
Of note, and even though twice-daily mycophenolate has been shown to be superior to once-daily azathioprine early post-transplant, more long-term data suggest that this advantage may not persist.6 Furthermore, a recent Cochrane review addressed the question of mycophenolate versus azathioprine as primary anti-proliferative immunosuppression for kidney transplant recipients; it concluded that "balancing the benefits and harms of the two drugs remains a major task of the transplant physician to decide which agent" is appropriate for the individual patient. 7 Moreover, once-daily immunosuppression with tacrolimus extended-release and once-daily azathioprine has been used with excellent results at a British center that focusses on AYA kidney transplant recipients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 13 Years 至 22 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 13-22 years
- •Tanner stage 4/5
- •"Stable" kidney transplant status, as determined by the primary transplant team
- •At minimum 1 year post-kidney transplant or patients meeting all of the above inclusion criteria except 4) who have instead been transitioned to azathioprine by the primary transplant team due to intolerability of mycophenolate mofetil secondary to adverse medication effects (i.e. neutropenia, gastrointestinal intolerance etc.)
排除标准
- •< Tanner stage 4
- •Kidney transplant performed at an institution other than Children's Hospital Colorado, Lurie Children's Hospital of Chicago, or Cincinnati Children's Hospital
- •Recipients of dual solid organ transplants (i.e. heart kidney, liver kidney).
研究组 & 干预措施
Adolescent and Young Adult (AYA) Kidney Transplant Recipients
AYA kidney transplant recipients will receive a Medication Event Monitoring System (MEMS) in the form of a medication bottle and cap system and once daily tacrolimus XR 1-10mg
干预措施: Medication Event Monitoring System (MEMS) (Other)
Adolescent and Young Adult (AYA) Kidney Transplant Recipients
AYA kidney transplant recipients will receive a Medication Event Monitoring System (MEMS) in the form of a medication bottle and cap system and once daily tacrolimus XR 1-10mg
干预措施: Once-Daily Tacrolimus extended release (Drug)
结局指标
主要结局
Adherence to medical therapies and medications: as assessed by Medication Event Monitoring System (MEMS) at Day 210
时间窗: Day 210
MEMS data will be accessed 6 months after transition to once-daily medications (retention adherence) and analyzed accordingly. Dates and times in which medication bottles were opened will be recorded.
Adherence to medical therapies and medications: as assessed by Medication Event Monitoring System (MEMS) at Day 30
时间窗: Day 30
MEMS data will be accessed prior to transition to once-daily medications (baseline adherence) and analyzed accordingly. Dates and times in which medication bottles were opened will be recorded.
Health-Related Quality of Life: as assessed by change in PedsQL
时间窗: Day 0, Day 60, Day 210
Pediatric Quality of Life (PedsQL) Transplant Module Version 3.0 will be used to assess quality of life prior to and after transition from twice to once daily immunosuppressant medication regimen. Health-related quality of life (HRQOL) has been defined as an individual's subjective experience of their illness, and the impact that illness and its treatment have on the individual's functioning in a variety of domains. The PedsQL is a 46-item self- and parent-report measure that rates HRQOL in 8 domains (medication adherence, medication side-effects, social relationship, physical discomfort, worries regarding health status, treatment anxiety, impact on appearance, and communication). The PedsQL Transplant Module assesses physical functioning, emotional functioning, social functioning, and school functioning and was developed through focus groups, cognitive interviews, pretesting, and field testing measurement development protocols. Higher scores indicate lower problems.
Adherence to medical therapies and medications: as assessed by Change in Tacrolimus Trough Concentration Variance
时间窗: Day 0, Day 30, Day 60, and Day 240
Tacrolimus trough goals between 4-7ng/mL as per Transplant Immunosuppression Protocols. Student T-test, repeated measures for parametric data). The standard deviation of tacrolimus troughs will be calculated from the 4 tacrolimus trough values obtained for clinical care purposes preceding Study Visit 1 (SD1). The standard deviation of tacrolimus troughs will be calculated again from the 4 tacrolimus trough values obtained for clinical care purposes preceding Study Visit 4 (SD2).
Adherence to medical therapies and medications:as assessed by Change in Adolescent Medication Barriers Scale (AMBS)
时间窗: Day 0, Day 60, Day 210
17 item scale that corresponds to the Parent Medication Barriers Scale (PMBS) with 16 items. Both have strong internal consistency and are scored on a 5-point Likert scale from Strongly Disagree to Strongly Agree. A total score can be calculated, and there are subdomains of disease frustration/adolescent issues, regimen adaptation/cognitive issues, and ingestion issues, with an additional parent reminder domain on the PMBS. Lower scores indicate less barriers to medication adherence.
Adherence to medical therapies and medications: as assessed by Change in The Medical Adherence Measure (MAM)
时间窗: Day 0, Day 60, Day 210
Semi-structured interview that has four general modules to assess adherence with medication, diet, exercise, and clinic attendance, as well as illness-specific modules. For the purpose of this study, the Medication and Clinic Attendance Modules will be completed. Non-adherence scores can be calculated based on the degree of adherence on a spectrum of 0%-100% adherent to capture the fluctuations and intricacies of occasional or slightly inconsistent adherence. Missed adherence score = number of doses missed out of the doses prescribed × 100%. Late adherence score = number of doses taken late out of the doses prescribed × 100%, where late is defined as greater than one hour later than the usual routine. Adherence is assessed for each medication separately and then averaged across medications.
Adherence to medical therapies and medications: as assessed by Medication Event Monitoring System (MEMS) at Day 60
时间窗: Day 60
MEMS data will be accessed the first month of transition to once-daily medications (intervention adherence) and analyzed accordingly. Dates and times in which medication bottles were opened will be recorded.
次要结局
- Long-term measures of graft and patient survival: as assessed by change in serum creatinine and urinary protein(Day 0, Day 30, Day 60, Day 210, and Day 240)
- Long-term measures of graft and patient survival: as assessed by change in markers of proteinuria(Day 30 and Day 210)
- Long-term measures of graft and patient survival: as assessed by number of episodes of rejection(Up to Day 240)
- Long-term measures of graft and patient survival: as assessed by change in presence of donor-specific antibody monitoring(Day 0 and Day 240)
- Long-term measures of graft and patient survival: as assessed by change in presence of BK virus screening results(Day 0 and Day 240)