Study to Evaluate the Safety and Efficacy of Extended Release Tacrolimus (Advagraf®) + Sirolimus (Rapamune®), Versus Extended Release Tacrolimus (Advagraf®) + Mycophenolate Mofetil in Kidney Transplant Patients

This study will compare the efficacy and safety of Extended Release Tacrolimus (Advagraf®) + Sirolimus (Rapamune®), versus Extended Release Tacrolimus (Advagraf®) + Mycophenolate mofetil in Kidney Transplant Patients.

Study Overview

• Status: Completed
• Conditions: Kidney Transplant Patients
• Intervention / Treatment: Drug: A) TEST; Drug: B) CONTROL

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daegu, Korea, Republic of
    • Kyungpook National Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital
  • Seoul, Korea, Republic of
    • Gangnam Severance Hospital
  • Seoul, Korea, Republic of
    • Korea University Anam Hospital
  • Ulsan, Korea, Republic of
    • Ulsan Univ Hospital
  • KyungKi Province
    • Suwon, KyungKi Province, Korea, Republic of
      • Ajou Univeristy Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients aged over 20 years
• Patient who is judged would have the benefits of the Extended Release Tacrolimus (Advagraf®)treatment by the investigator
• Patients has given written informed consent
• Patient is a recipient of primary or recipient of primary (a living kidney transplant, a cadaveric donor.)
• Patients has received an ABO compatible donor kidney.
• Complement-dependent Cytotoxic Crossmatch: CDC) result: negative
• Female patients of child bearing potential must have a negative urine or serum pregnancy test within 7 days prior to enrollment or upon hospitalization

Exclusion Criteria:

• Patient has previously received an organ transplant other than a kidney.
• Patient has a known hypersensitivity to tacrolimus, Sirolimus (Rapamune®),Mycophenolate mofetil.
• Desensitization
• HLA-identical
• Heart Disease; Heart failure (symptom, EF <45%)
• Lung Disease; Significant chronic obstructive pulmonary disease, restrictive lung disease
• Patient has an uncontrolled concomitant infection (including Hepatitis B, Hepatitis C) or any other unstable
• malignant tumor history in the 5years prior to enrollment. (except,squamous cell carcinoma)
• Patient has received a kidney transplant from non-heart beating donor
• Cold ischemic time > 30hrs
• Elevated AST and/or ALT levels greater than 3 times the upper value of the normal range of the investigational site
• (ANC)<1,500/mm3, (WBC)<2,500/ mm3, (PLT)<100,000/ mm3
• ATG: Anti-thymocyte globulin induction
• Medical condition that could interfere with the study objectives.
• Patient is currently taking or has been taking an investigational products in the 30 days prior to enrollment.
• Patient is currently taking or has been taking an prohibited medications in the 28 days prior to enrollment.
• Patient who is judged not to be adequate by the investigator owing to other reasons
• Patient is pregnant or lactating.
• Recipient or donor is known to be seropositive for human immunodeficiency virus.(HIV)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A) TEST	Drug: A) TEST; Extended Release Tacrolimus (Advagraf®)① Living The day before surgery: 0.2 mg/kg(morning dose) po, qd Morning on the day of surgery: 0.1 mg/kg po, qd After surgery, the capacity is adjusted according to the trough level. clinical significance, electrolyte level.② Cadaveric Before surgery at once : 0.1 mg/kg within 12hours before surgery. After surgery : 0.2mg/kg po. in the morning After that, the capacity is adjusted according to the trough level. clinical significance, electrolyte level.; Sirolimus (Rapamune®): After surgery : 2mg/kg po. within 24hrs after reperfusion. After that, the capacity is adjusted according to the trough level.; Other Names: 1. Test group : Extended Release Tacrolimus (Advagraf®) + Sirolimus (Rapamune®); Drug: B) CONTROL; Extended Release Tacrolimus (Advagraf®): Same as above.; Mycophenolate mofetil : After surgery : 500mg/kg po. within 24hrs after reperfusion. After that, daily dose: 1000mg bid; Other Names: 2. Control group: Extended Release Tacrolimus (Advagraf®) + Mycophenolate mofetil
Experimental: B) CONTROL	Drug: A) TEST; Extended Release Tacrolimus (Advagraf®)① Living The day before surgery: 0.2 mg/kg(morning dose) po, qd Morning on the day of surgery: 0.1 mg/kg po, qd After surgery, the capacity is adjusted according to the trough level. clinical significance, electrolyte level.② Cadaveric Before surgery at once : 0.1 mg/kg within 12hours before surgery. After surgery : 0.2mg/kg po. in the morning After that, the capacity is adjusted according to the trough level. clinical significance, electrolyte level.; Sirolimus (Rapamune®): After surgery : 2mg/kg po. within 24hrs after reperfusion. After that, the capacity is adjusted according to the trough level.; Other Names: 1. Test group : Extended Release Tacrolimus (Advagraf®) + Sirolimus (Rapamune®); Drug: B) CONTROL; Extended Release Tacrolimus (Advagraf®): Same as above.; Mycophenolate mofetil : After surgery : 500mg/kg po. within 24hrs after reperfusion. After that, daily dose: 1000mg bid; Other Names: 2. Control group: Extended Release Tacrolimus (Advagraf®) + Mycophenolate mofetil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failure rate in effectiveness of up to 12 months after kidney transplant	Biopsy confirmed acute rejection; Subjects and graft survival; Glomerular filtration rate (GFR); 24-hour urine test results at 12 months after kidney transplant: Urine protein, CrCl.	12 months after kidney transplant

Collaborators and Investigators

• Sponsor: Yonsei University

Publications and helpful links

General Publications

• Huh KH, Lee JG, Ha J, Oh CK, Ju MK, Kim CD, Cho HR, Jung CW, Lim BJ, Kim YS; RECORD Study. De novo low-dose sirolimus versus mycophenolate mofetil in combination with extended-release tacrolimus in kidney transplant recipients: a multicentre, open-label, randomized, controlled, non-inferiority trial. Nephrol Dial Transplant. 2017 Aug 1;32(8):1415-1424. doi: 10.1093/ndt/gfx093.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: September 4, 2012
• First Submitted That Met QC Criteria: September 6, 2012
• First Posted (Estimate): September 7, 2012

Study Record Updates

• Last Update Posted (Estimate): March 8, 2016
• Last Update Submitted That Met QC Criteria: March 7, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: RECORD study
• 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; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid; Sirolimus
• Other Study ID Numbers: 4-2011-0920