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Selection of Immunosuppression in Kidney Transplant Recipients Depending on Pre-transplant Donor-specific T-cell Reactivity. (SIRES)

This study has been completed.
Sponsor:
Collaborator:
Carlos III Health Institute
Information provided by (Responsible Party):
Josep M Grinyo, Hospital Universitari de Bellvitge
ClinicalTrials.gov Identifier:
NCT01195194
First received: April 19, 2010
Last updated: February 24, 2014
Last verified: February 2014

April 19, 2010
February 24, 2014
March 2008
June 2012   (final data collection date for primary outcome measure)
Percentage of biopsy-confirmed acute rejection episodes [ Time Frame: 6 months ] [ Designated as safety issue: No ]
To describe cumulative biopsy-confirmed acute rejection in both groups by intention to treat analysis.
Same as current
Complete list of historical versions of study NCT01195194 on ClinicalTrials.gov Archive Site
  • Percentage of steroid-sensitive acute rejection episodes [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To describe the percentage of steroid-sensitive acute rejections rejection in both groups by intention to treat analysis.
  • Percentage of acute rejection episodes requiring treatment with antilymphocyte antibodies. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To describe the need for antibody treatment in acute rejection episodes in both groups by intention to treat analysis.
  • Renal function estimated by Modification of Diet in Renal Disease (MDRD) formula. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To describe renal function measured by MDRD in both groups by intention to treat and "on therapy" analysis.
  • Proteinuria measured in g/day [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To describe proteinuria in g/day in both groups by intention to treat analysis.
  • Histology at month 6 protocol kidney allograft biopsy [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To describe histology at month 6 in both groups by intention to treat and "on therapy" analysis.
  • Percentage of patients with negative ELISPOT [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To describe percentage of patients with negative ELISPOT in both groups by intention to treat and "on therapy" analysis.
  • Percentage of patients in group A requiring CNI introduction. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    To describe the percentage of patients in group A requiring CNI introduction.
  • Percentage of patients presenting adverse events requiring study withdrawal [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    To describe adverse events in the whole group ("screening failure" plus "intention to treat") in both treatments groups.
  • Percentage of biopsy-confirmed acute rejection episodes [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To describe cumulative biopsy-confirmed acute rejection in both groups by intention to treat analysis.
  • Percentage of steroid-sensitive acute rejections rejection episodes [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To describe the percentage of steroid-sensitive acute rejections rejection in both groups by intention to treat analysis.
  • Percentage of acute rejection episodes requiring treatment with antilymphocyte antibodies [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To describe the need for antibody treatment in acute rejection episodes in both groups by intention to treat analysis.
  • Proteinuria measured in g/day [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To describe proteinuria in g/day in both groups by intention to treat analysis.
  • Percentage of patients with negative ELISPOT [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To describe percentage of patients with negative ELISPOT in both groups by intention to treat and "on therapy" analysis.
  • 1. Percentage of steroid-sensitive acute rejection episodes [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To describe the percentage of steroid-sensitive acute rejections rejection in both groups by intention to treat analysis.
  • 2. Percentage of acute rejection episodes requiring treatment with antilymphocyte antibodies. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To describe the need for antibody treatment in acute rejection episodes in both groups by intention to treat analysis.
  • 3. Renal function estimated by MDRD. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To describe renal function measured by MDRD in both groups by intention to treat and "on therapy" analysis.
  • 4. Proteinuria measured in g/day [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To describe proteinuria in g/day in both groups by intention to treat analysis.
  • 5. Histology at month 6 protocol kidney allograft biopsy [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To describe histology at month 6 in both groups by intention to treat and "on therapy" analysis.
  • 6. Percentage of patients with negative ELISPOT [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To describe percentage of patients with negative ELISPOT in both groups by intention to treat and "on therapy" analysis.
  • 7. Percentage of patients in group A requiring CNI introduction. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    To describe the percentage of patients in group A requiring CNI introduction.
  • 8. Percentage of patients presenting adverse events requiring study withdrawal [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    To describe adverse events in the whole group ("screening failure" plus "intention to treat") in both treatments groups.
  • 9. Percentage of biopsy-confirmed acute rejection episodes [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To describe cumulative biopsy-confirmed acute rejection in both groups by intention to treat analysis.
  • 10. Percentage of steroid-sensitive acute rejections rejection episodes [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To describe the percentage of steroid-sensitive acute rejections rejection in both groups by intention to treat analysis.
  • 11. Percentage of acute rejection episodes requiring treatment with antilymphocyte antibodies [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To describe the need for antibody treatment in acute rejection episodes in both groups by intention to treat analysis.
  • 12. Proteinuria measured in g/day [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To describe proteinuria in g/day in both groups by intention to treat analysis.
  • 13. Percentage of patients with negative ELISPOT [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To describe percentage of patients with negative ELISPOT in both groups by intention to treat and "on therapy" analysis.
Not Provided
Not Provided
 
Selection of Immunosuppression in Kidney Transplant Recipients Depending on Pre-transplant Donor-specific T-cell Reactivity.
Pilot Study of Selection of Either Calcineurin Inhibitor(CNI)-Based or CNI-free Immunosuppressive Regimen Depending on the Result of Pre-transplantation Donor-specific T-cell Reactivity Measured by Enzyme-linked Immunosorbent Spot(ELISPOT) in Standard-risk Kidney Recipients.

The objective is to assess if low pre-transplantation donor specific T-cell reactive patients measured by Enzyme-linked immunosorbent spot (ELISPOT)assay can be safely managed with Calcineurin inhibitor(CNI)-free Sirolimus(SRL)-based immunosuppression.

Non randomized, pilot, prospective, open-label trial.

Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Disorder Related to Renal Transplantation
Drug: PRE-TRANSPLANT (PRE=before)

All patients will start with Thymoglobulin 1 mg/kg before transplant followed by 0,5 mg/kg/d during the next 5 days (total accumulated 3,5 mg/kg).

Steroids will be administered at 0,25 mg/kg/d until month 3rd, followed by 0,1 mg/kg/d thereafter.

Mycophenolate Mofetil: Pre-transplant 2 grams iv. After transplantation 1g/12 hours, starting iv and changing to oral formulation as soon as patient starts with oral intake (targeting mycophenolic acid (MPA) C0h levels 2-5 µg/mL).

  • Experimental: A- negative pre-transplant ELISPOT
    Sirolimus: Start at 5 mg/day as soon as treatment allocation arrives to obtain targeting levels to 8 -15 ng/ml (immunoassay) in the first 3 months, followed by trough levels of 5-10 ng/ml.
    Intervention: Drug: PRE-TRANSPLANT (PRE=before)
  • Experimental: B- Positive pre-transplant ELISPOT
    Tacrolimus 0.1 mg/kg/12h starting as soon as treatment allocation arrives to obtain targeting troughs levels of 8-15 ng/ml the first 3 months, followed by trough levels of 5-10 ng/ml until the end of the study.
    Intervention: Drug: PRE-TRANSPLANT (PRE=before)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
61
June 2013
June 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Age of donor and recipient between 18 and 65 years.
  2. End-stage renal disease and scheduled to receive a primary or secondary renal allograft from a cadaveric, a living-unrelated, or a living-related donor. Patients scheduled for a second transplant must have maintained their primary graft for at least 6 months after transplantation, with the exception of graft failure due to technical reasons.
  3. Panel reactive antibody (PRA) ≤ 20%, with negative standard cross-match.
  4. Women of childbearing potential must have a negative serum pregnancy test before randomization.
  5. Women of childbearing potential must agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months following discontinuation of assigned treatment.
  6. Signed and dated informed consent prior to transplantation.

Exclusion Criteria:

  1. Multiple organ transplants
  2. Recipients of adult or pediatric en bloc kidney transplants or dual transplantation or non-heart beating donors.
  3. Evidence of active systemic or localized major infection.
  4. Evidence of infiltrate, cavitation, or consolidation on chest x-ray obtained during the screening/baseline evaluation.
  5. Use of any investigational drug or treatment up to 4 weeks prior to transplantation.
  6. Treatment with voriconazole, ketoconazole, itraconazole, fluconazole, clotrimazole, astemizole, pimozide, terfenadine, erythromycin, clarithromycin, telithromycin, troleandomycin, rifampin, rifabutin, or St. John's Wort that is not discontinued prior to randomization.
  7. Treatment with aminoglycosides, amphotericin B, cisplatin, cisapride, metoclopramide, cimetidine, bromocriptine, danazol, or other drugs associated with renal dysfunction that are not discontinued prior to randomization.
  8. Subjects with a screening/baseline total white blood cell count < 2,000/mm3 or absolute neutrophil count (ANC) < 500, platelet count < 100,000/mm3.
  9. Fasting triglycerides > 400 mg/dL (> 4.6 mmol/L) or fasting total cholesterol > 300 mg/dL (> 7.8 mmol/L) despite optimal lipid-lowering therapy.
  10. History of malignancy within 2 years of enrollment (except for adequately treated basal cell or squamous cell carcinoma of the skin).
  11. Auto-immune diseases inactive immunosuppressive treatment ( 3 months prior to inclusion).
  12. Patient with psychiatric disorders that could be non-compliance for the treatment.
  13. Non Caucasian patients.
  14. Active peptic ulcers that could produce intestinal absorption disorders.
  15. Subjects who are known to be human immunodeficiency virus(HIV) or hepatitis B virus (HBV) positive. Patients with hepatitis C virus (HCV) positive should be excluded if polymerase chain reaction (PCR) positive or transaminates values are ≥2 upper normal value (UNV).
  16. Diabetic patients.
  17. Body mass index higher than 30 Kg/m2.
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Spain
 
NCT01195194
SIRES, 2007-002378-68
Yes
Josep M Grinyo, Hospital Universitari de Bellvitge
Josep M Grinyo
Carlos III Health Institute
Principal Investigator: Josep M Grinyó, PhD MD Nephrology Department. Hospital de Bellvitge. Spain
Hospital Universitari de Bellvitge
February 2014

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