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Evaluate Efficacy Study of Combination Therapy of Everolimus and Low Dose Tacrolimus in Renal Allograft Recipients (PROTECT)

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ClinicalTrials.gov Identifier: NCT02036554
Recruitment Status : Unknown
Verified September 2014 by ChulWoo Yang, Seoul St. Mary's Hospital.
Recruitment status was:  Recruiting
First Posted : January 15, 2014
Last Update Posted : September 25, 2014
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
ChulWoo Yang, Seoul St. Mary's Hospital

Tracking Information
First Submitted Date  ICMJE December 23, 2013
First Posted Date  ICMJE January 15, 2014
Last Update Posted Date September 25, 2014
Study Start Date  ICMJE March 2013
Estimated Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 13, 2014)
Change from Baseline in Development of NODAT (Fasting glucose ≥ 126 mg/dL, Random glucose ≥ 200 mg/dL) at 12 months [ Time Frame: 0 to 12 month ]
To evaluate prevention effect of combination therapy of Everolimus and low-dose Tacrolimus in comparison with standard-dose Tacrolimus therapy with Mycophenolic acid on the New Onset Diabetes Mellitus after transplantation at 12 months after date of randomization.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 13, 2014)
  • Insulin resistance by HOMA-IR [ Time Frame: 0 to 12 months ]
    Change from Baseline(V2) in Insulin resistance by HOMA-IR at 12months(V6)
  • Insulin secretion by HOMA-beta [ Time Frame: 0 to 12 months ]
    Change from Baseline(V2) in insulin secretion by HOMA-beta at 12 months(V6)
  • OGTT (Fasting and PP2hr) [ Time Frame: 0 to 12 months ]
    Change from baseline in OGTT (Fasting and PP2hr) at 12 months(V6)
  • Needs for anti-diabetic medication or insulin [ Time Frame: at Baseline(V2) ]
    Needs for anti-diabetic medication or insulin at Baseline(V2)
  • Needs for anti-diabetic medication or insulin at 3 month(V3) [ Time Frame: at 3 month(V3) ]
    Needs for anti-diabetic medication or insulin at 3 month(V3)
  • Needs for anti-diabetic medication or insulin at 6 month(V4) [ Time Frame: at 6 month(V4) ]
    Needs for anti-diabetic medication or insulin at 6 month(V4)
  • Needs for anti-diabetic medication or insulin at 9 month(V5) [ Time Frame: at 9 month(V5) ]
    Needs for anti-diabetic medication or insulin at 9 month(V5)
  • Needs for anti-diabetic medication or insulin at 12 month(V6) [ Time Frame: at 12 month(V6) ]
    Needs for anti-diabetic medication or insulin at 12 month(V6)
  • Creatinine clearance (MDRD eGFR) at Baseline(V2) [ Time Frame: at Baseline(V2) ]
    Creatinine clearance (MDRD eGFR) at Baseline(V2)
  • Creatinine clearance (MDRD eGFR) at 3 month(V3) [ Time Frame: at 3 month(V3) ]
    Creatinine clearance (MDRD eGFR) at 3 month(V3)
  • Creatinine clearance (MDRD eGFR) at 6 month(V4) [ Time Frame: at 6 month(V4) ]
    Creatinine clearance (MDRD eGFR) at 6 month(V4)
  • Creatinine clearance (MDRD eGFR) at 9 month(V5) [ Time Frame: at 9 month(V5) ]
    Creatinine clearance (MDRD eGFR) at 9 month(V5)
  • Creatinine clearance (MDRD eGFR) at 12 month(V6) [ Time Frame: at 12 month(V6) ]
    Creatinine clearance (MDRD eGFR) at 12 month(V6)
  • 12 month graft survival [ Time Frame: at 12 months(V6) ]
    After date of randomization, evaluate graft survival rate at 12 months(V6)
  • 12 month patient survival rate [ Time Frame: at 12 months(V6) ]
    After date of randomization, evaluate patient survival rate at 12 months(V6)
  • Change from baseline in Microalbuminuria(MAU) at 12 months [ Time Frame: at 12 months(V6) ]
    Change from baseline in Microalbuminuria(MAU) at 12 months
  • Proportion of patients with significant proteinuria greater than 1g/gCr at Baseline(V2) [ Time Frame: at Baseline(V2) ]
    Proportion of patients with significant proteinuria greater than 1g/gCr at Baseline(V2)
  • Proportion of patients with significant proteinuria greater than 1g/gCr at 3 month(V3) [ Time Frame: at 3 month(V3) ]
    Proportion of patients with significant proteinuria greater than 1g/gCr at 3 month(V3)
  • Proportion of patients with significant proteinuria greater than 1g/gCr at 6 month(V4) [ Time Frame: at 6 month(V4) ]
    Proportion of patients with significant proteinuria greater than 1g/gCr at 6 month(V4)
  • Proportion of patients with significant proteinuria greater than 1g/gCr at 9 month(V5) [ Time Frame: at 9 month(V5) ]
    Proportion of patients with significant proteinuria greater than 1g/gCr at 9 month(V5)
  • Proportion of patients with significant proteinuria greater than 1g/gCr at 12 month(V6) [ Time Frame: at 12 month(V6) ]
    Proportion of patients with significant proteinuria greater than 1g/gCr at 12 month(V6)
  • Number of episode of biopsy proven acute rejection (BPAR) [ Time Frame: at 12 month(V6) ]
    Cumulative incidence rate of Biopsy Proven Acute Rejection(BPAR) at 12months(V6) after date of randomization.
  • Number of hospitalization of any cause (except admission for protocol biopsy) at Baseline(V2) [ Time Frame: at Baseline(V2) ]
    Number of hospitalization of any cause (except admission for protocol biopsy) at Baseline(V2)
  • Number of hospitalization of any cause (except admission for protocol biopsy) at 3 month(V3) [ Time Frame: at 3 month(V3) ]
    Number of hospitalization of any cause (except admission for protocol biopsy) at 3 month(V3)
  • Number of hospitalization of any cause (except admission for protocol biopsy) at 6 month(V4) [ Time Frame: at 6 month(V4) ]
    Number of hospitalization of any cause (except admission for protocol biopsy) at 6 month(V4)
  • Number of hospitalization of any cause (except admission for protocol biopsy) at 9 month(V5) [ Time Frame: at 9 month(V5) ]
    Number of hospitalization of any cause (except admission for protocol biopsy) at 9 month(V5)
  • Number of hospitalization of any cause (except admission for protocol biopsy) at 12 month(V6) [ Time Frame: at 12 month(V6) ]
    Number of hospitalization of any cause (except admission for protocol biopsy) at 12 month(V6)
  • Number of opportunistic infections (BKVN) at Baseline(V2) [ Time Frame: at Baseline(V2) ]
    Number of opportunistic infections (BKVN) at Baseline(V2)
  • Number of opportunistic infections (BKVN) at 12month(V6) [ Time Frame: at 12 month(V6) ]
    Number of opportunistic infections (BKVN) at 12month(V6)
  • Prevalence of NODAT at Baseline(V2) [ Time Frame: at Baseline(V2) ]
    Prevalence of NODAT at Baseline(V2)
  • Prevalence of NODAT at 3 month(V3) [ Time Frame: at 3 month(V3) ]
    Prevalence of NODAT at 3 month(V3)
  • Prevalence of NODAT at 6 month(V4) [ Time Frame: at 6 month(V4) ]
    Prevalence of NODAT at 6 month(V4)
  • Prevalence of NODAT at 9 month (V5) [ Time Frame: at 9 month (V5) ]
    Prevalence of NODAT at 9 month (V5)
  • Prevalence of NODAT at 12 month(V6) [ Time Frame: at 12 month(V6) ]
    Prevalence of NODAT at 12 month(V6)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluate Efficacy Study of Combination Therapy of Everolimus and Low Dose Tacrolimus in Renal Allograft Recipients
Official Title  ICMJE To Evaluate Prevention Effect Of Everolimus and Low-dose Tacrolimus in Comparison With Standard-dose Tacrolimus Therapy With Mycophenolic Acid on the New Onset Diabetes Mellitus After Transplantation in the Renal Allograft Recipients
Brief Summary To evaluate prevention effect of combination therapy of Everolimus and low-dose Tacrolimus in comparison with standard-dose Tacrolimus therapy with Mycophenolic acid on the New Onset Diabetes Mellitus after transplantation in the renal allograft recipients
Detailed Description An open-label, randomized, multi-center, comparative parallel study to evaluate prevention effect of combination therapy of Everolimus and low-dose Tacrolimus in comparison with standard-dose Tacrolimus therapy with Mycophenolic acid on the New Onset Diabetes Mellitus after transplantation in the renal allograft recipients: PROTECT study
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Kidney; Complications, Allograft
Intervention  ICMJE
  • Drug: Everolimus
    Decrease the level of Tacrolimus and add on Everolimus instead of Mycophenolic acid which is standard treatment.
    Other Name: Certican
  • Drug: Tacrolimus
    Decrease the level of Tacrolimus and add on Everolimus instead of Mycophenolic acid which is standard treatment.
    Other Name: Tacroli
  • Drug: Mycophenolic acid
    Decrease the level of Tacrolimus and add on Everolimus instead of Mycophenolic acid which is standard treatment.
    Other Name: Cellcept
Study Arms  ICMJE
  • Experimental: Tacrolimus plus Everolimus
    Low dose Tacrolimus + Everolimus
    Interventions:
    • Drug: Everolimus
    • Drug: Tacrolimus
  • Active Comparator: Tacrolimus plus Mycophenolic acid
    standard dose Tacrolimus + Mycophenolic acid
    Interventions:
    • Drug: Tacrolimus
    • Drug: Mycophenolic acid
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: January 13, 2014)
234
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2015
Estimated Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age ≥ 20 year old
  2. At least 3 months after kidney transplantation
  3. Subject who is using Tacrolimus ± purine synthesis inhibitor + steroid without change within the past 3 months (except the dosage)
  4. MDRD eGFR ≥ 50 mL/min or serum creatinine < 2.0mg/dL within the past 3 months in the 6months after kidney transplantation
  5. Rate of change of serum creatinine < +30% within the past 3 months in the 6months after kidney transplantation (if serum creatinine decreased, without rate of change is inclusion possible. if serum creatinine result was normal,regardless of the rate of change is able to register.)
  6. Urine protein/creatinine ratio < 1g/g Cr (spot urine) Subject who is not applicable to the diagnostic criteria NODAT on
  7. the baseline in the 6months after kidney transplantation
  8. Subjects who agree with written informed consent

Exclusion Criteria:

  1. Subjects who received combined non-renal transplantation
  2. Subject who received re-transplantation
  3. ABO blood group incompatible(when anti-ABO Antibody titer <1:128 is inclusion possible.)
  4. Sensitized patients before transplantation

    • Pretransplant or peak PRA titer > 50%
    • Pretransplant T cell cytotoxicity crossmatch (+)
  5. HLA-identical living related donor
  6. Subject who has diabetes mellitus / NODAT before transplantation
  7. Subject who has suffered acute rejection episode within the past 3 months in the 6months after kidney transplantation
  8. Subject with hypersensitivity to everolimus
  9. Subject who should continue nephrotoxic drug until enrollment (Aminoglycoside, amphotericin B, cisplatin)
  10. Subject with GI disorder that might interfere with the ability to absorb oral medication. (eg, gastrectomy or insufficiently treated diabetic gastroenteropathy)
  11. Subjects with active peptic ulcer
  12. HIV, HBsAg, or HCV Ab tests (+)
  13. Abnormal liver function test (AST or ALT or total bilirubin> upper normal limit x3)
  14. ANC <1.5*109/L or WBC <2.5*109/L or platelet <75*109/L
  15. Treatment with an investigational drug within 30 days preceding the first dose of trial medication
  16. Women who are either pregnant, lactating, planning to become pregnant in the next 12 months.
  17. Subjects with history of cancer(except successfully treated), localized nonmelanocytic skin cancer, PTLD(Post-transplant lymphoproliferative disorder)
  18. Subjects with clinically significant infections within the past 4 weeks in the 6months after kidney transplantation
  19. Subjects who took major surgery within the past 4 weeks in the 6months after kidney transplantation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02036554
Other Study ID Numbers  ICMJE CRAD001AKR11T
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party ChulWoo Yang, Seoul St. Mary's Hospital
Study Sponsor  ICMJE Seoul St. Mary's Hospital
Collaborators  ICMJE Novartis
Investigators  ICMJE
Principal Investigator: Chul-Woo Yang, MD St Mary's Hospital, London
PRS Account Seoul St. Mary's Hospital
Verification Date September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP