Overview

This trial is active, not recruiting.

Conditions immunosuppression, cardiovascular diseases, kidney transplantation
Treatments once daily tacrolimus, twice daily tacrolimus
Phase phase 4
Sponsor University of Saskatchewan
Collaborator Astellas Pharma Canada, Inc.
Start date January 2013
End date June 2016
Trial size 75 participants
Trial identifier NCT01702207, ESTTEROD

Summary

Current standard prophylactic immunosuppression in renal transplantation includes tacrolimus, a calcineurin inhibitor, dosed twice daily. In Canada, oral tacrolimus has been available as a twice daily formulation marketed as Prograf® since 1997. It has recently become available in an extended release formulation called Advagraf®, which is dosed once daily. Advagraf® has been demonstrated to be therapeutically equivalent to Prograf® in the renal transplant maintenance population, and as a result it has been is approved as an alternative to the twice daily formulation in these patients. There is an evolving and expanding positive clinical experience with Advagraf® in kidney transplantation and it has shown to be preferred by many patients, due to the diminished dosing frequency. In clinical trials, Advagraf® has been shown to have other potential benefits over Prograf® such as less inter and intra-patient variability, improved cardiovascular profiles, and improved kidney function. Compared to Prograf®, Advagraf® also has a lower Cmin or 'trough' concentration as well as a lower Cmax or 'peak' concentration. The purpose of this study is to convert stabilized renal transplant patients currently receiving Prograf® to Advagraf®, to investigate these potential therapeutic benefits.

The Framingham Risk Score and the Reynold's Risk Score are currently recommended by the Canadian Cardiovascular Society (CCS) to predict 10-year cardiovascular risk in the general population. Surrogate markers are widely used in clinical trials to shorten follow-up durations. In this study, the investigators will use the Framingham Risk Score and Reynold's Risk Score to quantify changes in estimated cardiovascular risk. The investigators also intend to examine novel inflammatory markers to investigate cardiovascular risk.

The investigators hypothesize that the more consistent drug exposure and lower Cmax noted with Advagraf® will decrease Framingham Risk Score, Reynolds Risk score as well as markers of inflammation in kidney transplant recipients.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model crossover assignment
Masking open label
Primary purpose supportive care
Arm
(Active Comparator)
Treatment Arm - Subjects are switched from the tacrolimus twice daily (Prograf®) to the once daily formulation (Advagraf®) to maintain a trough tacrolimus level of 5-8.
once daily tacrolimus Advagraf®
Subjects switched from the tacrolimus twice daily (Prograf®) to the once daily formulation (Advagraf®) to maintain a trough tacrolimus level of 5-8.
(Active Comparator)
Control Arm - Subjects are kept on Prograf® which is the Twice Daily Tacrolimus
twice daily tacrolimus Prograf®
Subjects are kept on Prograf® which is the Twice Daily Tacrolimus

Primary Outcomes

Measure
Change in the Framingham risk scores and change in the Reynolds Risk Score.
time frame: Visit 1, Visit 3 (12 months)

Secondary Outcomes

Measure
Comparison in GFR between the two groups.
time frame: Visit 1, Visit 3 (12 months)
Effect of therapy on CV biomarkers, insulin resistance and lipid profile.
time frame: Visit 1, Visit 3 (12 months)
To look at change in the glomerular filtration rate (GFR) over the duration of the study.
time frame: Vist 1, Visit 3 (12 months)

Eligibility Criteria

Male or female participants from 18 years up to 74 years old.

Inclusion Criteria: - Kidney transplant patients currently stable on the twice-daily formulation and who are followed as outpatients. - Stability is defined as change in serum creatinine of less than 10% over the last two months - Age 18-74 years old - At least six months after transplantation - Lack of rejection within the last 12 weeks - Serum creatinine less than 300 umol/L at enrolment - Negative urine pregnancy test for female patients of childbearing potential - Consent to the study - Not included in a clinical trial within the last 90 days Exclusion Criteria: - Patients with other types of solid organ transplants - Patients with any form of substance abuse or psychiatric disorder. - Patients with acute or chronic diarrhea - Patients receiving anti-lymphocyte treatment for rejection within the last six months - Patients on cyclosporine and or not receiving a mycophenolate derivative. - Patients with significant liver disease defined as having an elevated bilirubin by at least two times the upper value of the normal range - Patients who have any unstable medical condition that could interfere with the study - Patients with chronic viral infection with HIV, Hep C and HCV. - Presence of any acute illness requiring admission to the hospital for the last 4 weeks - Pregnancy - Significant cardiovascular event such as MI, stroke or TIA within the last 12 weeks or uncontrolled hypertension. - Immunosuppressant changes within the last month.

Additional Information

Official title A One-Year, Prospective, Randomized, Controlled Study Evaluating The Efficacy Of Switching From The Twice Daily Tacrolimus Formulation To The Extended Release, Once Daily Formulation To Reduce The Framingham Cardiovascular Risk Scores.
Principal investigator Ahmed Shoker, MD
Trial information was received from ClinicalTrials.gov and was last updated in June 2015.
Information provided to ClinicalTrials.gov by University of Saskatchewan.