Study to Evaluate the Safety and Efficacy of Advagraf vs Prograf in Kidney Transplantation Patients 1 Month After the Transplantation (AdProCISE)

Multicenter, Open-label, Parallel Clinical Investigation of the Safety and Efficacy of Advagraf® (Extended Release Tacrolimus) vs. Prograf® (Tacrolimus) in de Novo Kidney Recipients 1 Month After Kidney Transplantation

To investigate the efficacy, safety, and drug compliance of Advagraf® (Extended Release Tacrolimus) by comparing the Advagraf® + steroid + Mycophenolate Mofetil combined therapy and the Prograf® + steroid + Mycophenolate Mofetil combined therapy in de novo kidney recipients 1 month after kidney transplantation.

Study Overview

• Status: Completed
• Conditions: de Novo Kidney Transplantation
• Intervention / Treatment: Drug: Prograf; Drug: Advagraf; Drug: Corticosteroid; Drug: Mycophenolate mofetil

Detailed Description

This study is a multicenter, open-label, randomized, parallel, and comparative clinical trial. All the enrolled subjects will be treated with Prograf® (Tacrolimus), Basilixumab, Corticosteroids, and Mycophenolate Mofetil to suppress their immune system for one month (30 days) after their kidney transplant. After the one month, the experimental group (30 subjects) will be treated with Advagraf® (Extended Release Tacrolimus) instead of Prograf® (Tacrolimus), and the Corticosteroids and Mycophenolate Mofetil will be maintained. The control group (30 subjects) will continuously receive Prograf® (Tacrolimus), Corticosteroids, and Mycophenolate Mofetil. The clinical progress of the subjects in the experimental and control groups up to six months after their transplant will be investigated and compared.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
  • Suwon, Korea, Republic of
  • Ulsan, Korea, Republic of

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who are planning to receive a kidney from a deceased/cadaveric donor or a living non-related/related donor
• Patients who are planning to undergo kidney transplantation through a 15- 65-year-old donor
• Patients who are willing and able to participate in this study, who signed the informed consent form after following the appropriate informed consent process, and who can visit the center based on the study schedule in the protocol.

Exclusion Criteria:

• Patients who had received a kidney or another organ and who will receive other organs with the kidney or two kidneys
• Patients who will receive a kidney from a cadaveric donor whose heart is no longer beating or from an organ donor after cardiac death [Patients, however, who will receive a kidney from a marginal donor (based on KONOS) can be enrolled based on the principal investigator's judgment.]
• Patients who will receive a kidney from a donor whose ABO blood type is not compatible with that of the recipient or who had positive lymphocyte cross-match (LCM) results
• Patients who will receive a kidney from a related donor who showed HLA-0 mismatch (identical) (If the donor is not related to the patient or is deceased, however, the patient can be enrolled in this study even if the patient showed HLA-0 mismatch or HLA-6 antigen match.)
• Patients who previously underwent or are planning to undergo transplantation of their extra-renal solid organ or bone marrow/stem cell
• Patients who were diagnosed with cancer in the last five years [ Patients, however, who have recovered from skin cancer (squamous cell/basal cell carcinoma) can be enrolled.]
• Patients or donors who have positive HIV, HBsAg, or anti-HCV test results
• Patients who have a history of hypersensitivity or allergy [that required acute (within four weeks)/chronic treatment] to the investigated drug or another drug with a similar chemical structure (e.g., Tacrolimus).
• Patients who were treated with other investigated drugs within 30 days from their study enrollment
• Patients who are planning to be pregnant, or who are pregnant or breastfeeding and who are not planning to use any contraceptive method during the study period.
• Patients who were addicted to drugs/alcohol within six months of their study enrollment or who have a mental illness that makes appropriate communication with them impossible

• Patients who showed the following result in the assessment prior to the kidney transplantation

  • Any of their liver panels (AST, ALT, ALKP, and total bilirubin) three times higher than the normal range
  • Absolute neutrophil count < 1,500/mm3, leukocytes < 2,500/mm3, or platelet < 100,000/mm3

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Advagraf group	Drug: Advagraf; oral; Other Names: tacrolimus; Drug: Corticosteroid; oral; Drug: Mycophenolate mofetil; oral
ACTIVE_COMPARATOR: Prograf group	Drug: Prograf; oral; Other Names: tacrolimus, FK506; Drug: Corticosteroid; oral; Drug: Mycophenolate mofetil; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of efficacy failure (treated-BCAR, biopsy-confirmed acute rejection, graft loss rate, death, or follow-up failure)	until 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival rate		at 6 months after treatment
Kidney function (eGFR)	assessment of eGFR using the Nankivell method	at 6 months
24-hour urine protein and creatinine clearance rate(CCR)		at 6 months
Incidence of new-onset diabetes after kidney transplantation (NODAT)		until 6 months
Safety assessed by the incidence of adverse events, physical exam, and labo-tests		until 6 months

Collaborators and Investigators

• Sponsor: Astellas Pharma Korea, Inc.

Publications and helpful links

General Publications

• Oh CK, Huh KH, Lee JS, Cho HR, Kim YS. Safety and efficacy of conversion from twice-daily tacrolimus to once-daily tacrolimus one month after transplantation: randomized controlled trial in adult renal transplantation. Yonsei Med J. 2014 Sep;55(5):1341-7. doi: 10.3349/ymj.2014.55.5.1341.

Helpful Links

• Link to Results on JAPIC - enter 140532 in the JapicCTI-RNo. field

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (ACTUAL): June 1, 2012
• Study Completion (ACTUAL): June 1, 2012

Study Registration Dates

• First Submitted: December 4, 2012
• First Submitted That Met QC Criteria: December 4, 2012
• First Posted (ESTIMATE): December 5, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): October 10, 2014
• Last Update Submitted That Met QC Criteria: October 8, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: immunosuppressant; NODAT; new-onset diabetes after kidney transplantation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid
• Other Study ID Numbers: ADV-KT-01