Immunosuppressant Medication Dosed Daily After Kidney Transplant

NCT04156204 | Terminated Early Phase 1 DMC FDA Drug

• 1 other identifier: 17-2311
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Kidney Transplant Rejection; Medication Adherence

Outcome Measures

Primary Outcomes (7)

• Health-Related Quality of Life: as assessed by change in PedsQL

  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

  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

  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

  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

  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)

  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)

  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

Secondary Outcomes (5)

• 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

Study Arms (1)

Adolescent and Young Adult (AYA) Kidney Transplant Recipients

EXPERIMENTAL

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

Other: Medication Event Monitoring System (MEMS); Drug: Once-Daily Tacrolimus extended release

Interventions

Medication Event Monitoring System (MEMS) OTHER

AYA kidney recipients will receive a Medication Event Monitoring System (MEMS) via medication bottle and cap system

Adolescent and Young Adult (AYA) Kidney Transplant Recipients

Once-Daily Tacrolimus extended release DRUG

AYA kidney recipients will receive once daily tacrolimus XR 1-10mg daily

Also known as: Envarus XR

Adolescent and Young Adult (AYA) Kidney Transplant Recipients

Eligibility Criteria

• Age: 13 Years - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 13-22 years
• Tanner stage 4/5
• "Stable" kidney transplant status, as determined by the primary transplant team

You may not qualify if:

• \< 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).

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Related Publications (7)

• Foster BJ, Dahhou M, Zhang X, Platt RW, Samuel SM, Hanley JA. Association between age and graft failure rates in young kidney transplant recipients. Transplantation. 2011 Dec 15;92(11):1237-43. doi: 10.1097/TP.0b013e31823411d7.

  PMID: 22124283 BACKGROUND

• Sabaté, E (2003) Adherence to long-term therapies: evidence for action. World Health Organization, Geneva

  BACKGROUND

• Steinberg EA, Moss M, Buchanan CL, Goebel J. Adherence in pediatric kidney transplant recipients: solutions for the system. Pediatr Nephrol. 2018 Mar;33(3):361-372. doi: 10.1007/s00467-017-3637-0. Epub 2017 Mar 27.

  PMID: 28349215 BACKGROUND

• Min SI, Ha J, Kang HG, Ahn S, Park T, Park DD, Kim SM, Hong HJ, Min SK, Ha IS, Kim SJ. Conversion of twice-daily tacrolimus to once-daily tacrolimus formulation in stable pediatric kidney transplant recipients: pharmacokinetics and efficacy. Am J Transplant. 2013 Aug;13(8):2191-7. doi: 10.1111/ajt.12274. Epub 2013 Jun 4.

  PMID: 23734831 BACKGROUND

• Heffron TG, Pescovitz MD, Florman S, Kalayoglu M, Emre S, Smallwood G, Wisemandle K, Anania C, Dhadda S, Sawamoto T, Keirns J, Fitzsimmons W, First MR. Once-daily tacrolimus extended-release formulation: 1-year post-conversion in stable pediatric liver transplant recipients. Am J Transplant. 2007 Jun;7(6):1609-15. doi: 10.1111/j.1600-6143.2007.01803.x.

  PMID: 17511684 BACKGROUND

• Clayton PA, McDonald SP, Chapman JR, Chadban SJ. Mycophenolate versus azathioprine for kidney transplantation: a 15-year follow-up of a randomized trial. Transplantation. 2012 Jul 27;94(2):152-8. doi: 10.1097/TP.0b013e31825475a3.

  PMID: 22728292 BACKGROUND

• Wagner M, Earley AK, Webster AC, Schmid CH, Balk EM, Uhlig K. Mycophenolic acid versus azathioprine as primary immunosuppression for kidney transplant recipients. Cochrane Database Syst Rev. 2015 Dec 3;2015(12):CD007746. doi: 10.1002/14651858.CD007746.pub2.

  PMID: 26633102 BACKGROUND

MeSH Terms

Conditions

Medication Adherence

Condition Hierarchy (Ancestors)

Patient Compliance; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Study Officials

• Jens Goebel, MD

  Children's Hospital Colorado

  PRINCIPAL INVESTIGATOR

• Mary Chandran, MD

  Children's Hospital Colorado

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Longitudinal Pilot Study

Study Record Dates

• First Submitted: November 1, 2019
• First Posted: November 7, 2019
• Study Start: November 20, 2019
• Primary Completion: November 27, 2020
• Study Completion: November 27, 2020
• Last Updated: December 2, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)