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Evaluation Of Switching From Twice Daily Tacrolimus To Once Daily Formulation On Cardiovascular Risk (ESTTEROD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University of Saskatchewan
Sponsor:
Collaborator:
Astellas Pharma Canada, Inc.
Information provided by (Responsible Party):
University of Saskatchewan
ClinicalTrials.gov Identifier:
NCT01702207
First received: September 27, 2012
Last updated: January 9, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Immunosuppression
Cardiovascular Diseases
Kidney Transplantation
Drug: Once Daily Tacrolimus
Drug: Twice Daily Tacrolimus
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Supportive Care
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.

Resource links provided by NLM:


Further study details as provided by University of Saskatchewan:

Primary Outcome Measures:
  • Change in the Framingham risk scores and change in the Reynolds Risk Score. [ Time Frame: Visit 1, Visit 3 (12 months) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparison in GFR between the two groups. [ Time Frame: Visit 1, Visit 3 (12 months) ] [ Designated as safety issue: No ]
  • Effect of therapy on CV biomarkers, insulin resistance and lipid profile. [ Time Frame: Visit 1, Visit 3 (12 months) ] [ Designated as safety issue: Yes ]
    CV biomarkers will be assessed by luminex and insulin resistance and lipid profile will be assessed by the Metabolic Syndrome

  • To look at change in the glomerular filtration rate (GFR) over the duration of the study. [ Time Frame: Vist 1, Visit 3 (12 months) ] [ Designated as safety issue: No ]

Estimated Enrollment: 75
Study Start Date: January 2013
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Once Daily Tacrolimus
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.
Drug: Once Daily Tacrolimus
Subjects switched from the tacrolimus twice daily (Prograf®) to the once daily formulation (Advagraf®) to maintain a trough tacrolimus level of 5-8.
Other Name: Advagraf®
Active Comparator: Twice Daily Tacrolimus
Control Arm - Subjects are kept on Prograf® which is the Twice Daily Tacrolimus
Drug: Twice Daily Tacrolimus
Subjects are kept on Prograf® which is the Twice Daily Tacrolimus
Other Name: Prograf®

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01702207

Contacts
Contact: Sandra Lockhart 306-655-5990
Contact: Ahmed Shoker 306 655 5934

Locations
Canada, Saskatchewan
St Paul's Hospital Recruiting
Saskatoon, Saskatchewan, Canada, S7M0Z9
Contact: Sandra Lockhart    306 655 5934      
Contact: Ahmed Shoker, MD    306 655 5934      
Sponsors and Collaborators
University of Saskatchewan
Astellas Pharma Canada, Inc.
Investigators
Principal Investigator: Ahmed Shoker, MD University of Saskatchewan
  More Information

No publications provided

Responsible Party: University of Saskatchewan
ClinicalTrials.gov Identifier: NCT01702207     History of Changes
Other Study ID Numbers: ESTTEROD
Study First Received: September 27, 2012
Last Updated: January 9, 2013
Health Authority: Canada: Ethics Review Committee

Keywords provided by University of Saskatchewan:
Prograf®
Advagraf®
tacrolimus
kidney transplant
renal transplant
cardiovascular risk
Framingham Risk
Reynolds Risk
immunosuppression

Additional relevant MeSH terms:
Cardiovascular Diseases
Tacrolimus
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 27, 2014