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Immunosuppressant Medication Dosed Daily After Kidney Transplant

2020년 11월 30일 업데이트: University of Colorado, Denver

Kidney Immunosuppression Dosed Daily Only (KIDDO) - A Pilot Study

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.

연구 개요

상세 설명

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.

연구 유형

중재적

등록 (실제)

1

단계

  • 초기 1단계

연락처 및 위치

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연구 장소

    • Colorado
      • Aurora, Colorado, 미국, 80045
        • Children's Hospital Colorado

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

13년 (어린이, 성인)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

Inclusion Criteria:

  1. Age 13-22 years
  2. Tanner stage 4/5
  3. "Stable" kidney transplant status, as determined by the primary transplant team
  4. 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.)

Exclusion Criteria:

  1. < Tanner stage 4
  2. Kidney transplant performed at an institution other than Children's Hospital Colorado, Lurie Children's Hospital of Chicago, or Cincinnati Children's Hospital
  3. Recipients of dual solid organ transplants (i.e. heart kidney, liver kidney).

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 다른
  • 할당: 해당 없음
  • 중재 모델: 단일 그룹 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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
AYA kidney recipients will receive a Medication Event Monitoring System (MEMS) via medication bottle and cap system
AYA kidney recipients will receive once daily tacrolimus XR 1-10mg daily
다른 이름들:
  • Envarus XR

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Health-Related Quality of Life: as assessed by change in PedsQL
기간: 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.
Day 0, Day 60, Day 210
Adherence to medical therapies and medications: as assessed by Medication Event Monitoring System (MEMS) at Day 30
기간: 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.
Day 30
Adherence to medical therapies and medications: as assessed by Medication Event Monitoring System (MEMS) at Day 60
기간: 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.
Day 60
Adherence to medical therapies and medications: as assessed by Medication Event Monitoring System (MEMS) at Day 210
기간: 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.
Day 210
Adherence to medical therapies and medications: as assessed by Change in Tacrolimus Trough Concentration Variance
기간: 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).

Day 0, Day 30, Day 60, and Day 240
Adherence to medical therapies and medications:as assessed by Change in Adolescent Medication Barriers Scale (AMBS)
기간: 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.
Day 0, Day 60, Day 210
Adherence to medical therapies and medications: as assessed by Change in The Medical Adherence Measure (MAM)
기간: 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.
Day 0, Day 60, Day 210

2차 결과 측정

결과 측정
측정값 설명
기간
Long-term measures of graft and patient survival: as assessed by change in serum creatinine and urinary protein
기간: Day 0, Day 30, Day 60, Day 210, and Day 240
Markers of graft function will be assessed by measuring levels of serum creatinine and urinary protein. Lower serum creatinine and urinary protein indicate better long-term graft and patient survival.
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
기간: Day 30 and Day 210
Markers of proteinuria will be assessed by urinalysis and random urinary protein/creatinine ratio. Lower urinary protein/creatinine ratio indicates better long-term measures of graft and patient survival.
Day 30 and Day 210
Long-term measures of graft and patient survival: as assessed by number of episodes of rejection
기간: Up to Day 240
Graft rejection episodes will be determined to have occurred if indicated by transplant biopsy results. Occurrences of graft rejection episodes among participants will be assessed up to Day 240.
Up to Day 240
Long-term measures of graft and patient survival: as assessed by change in presence of donor-specific antibody monitoring
기간: Day 0 and Day 240
Presence of donor-specific antibodies (DSA) prior to and after initiation of intervention.
Day 0 and Day 240
Long-term measures of graft and patient survival: as assessed by change in presence of BK virus screening results
기간: Day 0 and Day 240
Includes assessing the viral load to monitor presence of BK virus.
Day 0 and Day 240

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여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

수사관

  • 수석 연구원: Jens Goebel, MD, Children's Hospital Colorado
  • 수석 연구원: Mary Chandran, MD, Children's Hospital Colorado

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

일반 간행물

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2019년 11월 20일

기본 완료 (실제)

2020년 11월 27일

연구 완료 (실제)

2020년 11월 27일

연구 등록 날짜

최초 제출

2019년 11월 1일

QC 기준을 충족하는 최초 제출

2019년 11월 5일

처음 게시됨 (실제)

2019년 11월 7일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2020년 12월 2일

QC 기준을 충족하는 마지막 업데이트 제출

2020년 11월 30일

마지막으로 확인됨

2020년 11월 1일

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Medication Event Monitoring System (MEMS)에 대한 임상 시험

3
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