Comparison of Medication Adherence Between Once and Twice Daily Tacrolimus in Stable Renal Transplant Recipients

Comparison of Medication Adherence Between Once Daily Tacrolimus (Advagraf®) and Twice Daily Tacrolimus (Prograf®) Administration in Stable Renal Transplant Recipients - a Randomized Study

A critical aspect of real-world functioning following kidney transplantation involves how adherent individuals are to their medication regimens. Regardless of the possible dangers of failing to adhere to anti-rejection medications, such as increased graft rejection, studies have reported rates of non-adherence at almost 50% following renal transplant.

The Cognitive Aging Laboratory under the direction of Dr. Wendy Thornton, at Simon Fraser University, has previously identified relationships between several potentially important cognitive and psychosocial variables, and self-reported medication adherence in renal transplant recipients, including depressive symptoms, as well as everyday and traditional cognitive functioning [4]. The possibility that changes in dosing regimens for a given medication may have an additional impact on medication adherence presents an important issue worth further exploration.

The current study will allow for more thorough delineation of the roles of psychosocial and cognitive predictors of adherence with state-of-the-art monitoring techniques. In addition, the investigators will assess whether different dosing formulations of tacrolimus impact adherence behaviors in renal transplant recipients.

The proposed research has two primary aims to examine:

1. To examine the role of cognitive and psychosocial variables in predicting medication adherence in renal transplant recipients.
2. To examine whether different formulations of tacrolimus (once per day dosing versus twice per day dosing) will impact medication adherence in renal transplant recipients.

Study Overview

• Status: Completed
• Conditions: Renal Transplant; Renal Disease
• Intervention / Treatment: Drug: Tacrolimus - Prograf® twice daily formulation; Drug: Tacrolimus - Advagraf® once daily formulation

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Solid Organ Transplant Clinic, Vancouver General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• a minimum of one year post renal transplant with a successful kidney graft and stable renal function (estimated glomerular filtration rate [GFR (glomerular filtration rate)] above 25 ml/minute per 1.73 m2).
• currently prescribed tacrolimus
• able to swallow pills
• a minimum of grade six education
• fluent in the English language.

Exclusion Criteria:

• refusal to or inability to give written informed consent.
• any visual, hearing or other sensory/motor impairments which may interfere with the testing procedures.
• have had a stroke determined to be of significant severity
• have had a head injury determined to be of significant severity
• have a current psychiatric diagnosis determined to be of significant severity
• have the presence of an acute illness (e.g., metastatic cancer), neurological disease, and other major organ failure (e.g., end stage liver disease)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Prograf®; Prograf® is a twice daily formulation of tacrolimus	Drug: Tacrolimus - Prograf® twice daily formulation; twice daily, dosage will be as determined by best treatment for each participant, duration of study period will be 4 months for each participant; Other Names: Prograf®
Experimental: Advagraf®; Advagraf® is a once daily formulation of tacrolimus	Drug: Tacrolimus - Advagraf® once daily formulation; once daily, dosage will be as determined by best treatment for each participant, duration of study period will be 4 months for each participant; Other Names: Advagraf®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
electronic monitor of medication taking	electronic bottle tops will be used to monitor medication adherence using MEMS (medication event monitoring system) Caps technology for a period of 4 months.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
blood levels of medication	blood levels of tacrolimus will be monitored throughout the study.	4 months
self-reported medication adherence	self-report medication adherence questionnaires will also be used to assess medication adherence.	4 months
pharmacy refill data	pharmacy refill data from the hospital pharmacy where all participants receive their medications will also be examined to determine medication adherence.	4 months

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: Simon Fraser University; Astellas Pharma Canada, Inc.
• Investigators: Principal Investigator: R. Jean Shapiro, M.D., University of British Columbia; Principal Investigator: Wendy Loken Thornton, Ph.D., Simon Fraser University; Principal Investigator: Nilufar Partovi, Pharm.D., University of British Columbia; Principal Investigator: Theone SE Paterson, M.A., Simon Fraser University

Publications and helpful links

General Publications

• Mellon L, Doyle F, Hickey A, Ward KD, de Freitas DG, McCormick PA, O'Connell O, Conlon P. Interventions for increasing immunosuppressant medication adherence in solid organ transplant recipients. Cochrane Database Syst Rev. 2022 Sep 12;9(9):CD012854. doi: 10.1002/14651858.CD012854.pub2.
• Paterson TSE, Demian M, Shapiro RJ, Loken Thornton W. Impact of Once- Versus Twice-Daily Tacrolimus Dosing on Medication Adherence in Stable Renal Transplant Recipients: A Canadian Single-Center Randomized Controlled Trial. Can J Kidney Health Dis. 2019 Aug 17;6:2054358119867993. doi: 10.1177/2054358119867993. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2011
• Primary Completion (Actual): October 30, 2014
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: April 11, 2011
• First Submitted That Met QC Criteria: April 12, 2011
• First Posted (Estimate): April 13, 2011

Study Record Updates

• Last Update Posted (Actual): May 17, 2018
• Last Update Submitted That Met QC Criteria: May 14, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: depression; cognition; kidney transplant; Self-efficacy; medication adherence; tacrolimus; neuropsychological; everyday problem solving
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: H11-00446