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

NCT01195194 | Completed Phase 4 DMC

• 2 other identifiers: SIRES2007-002378-68
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Disorder Related to Renal Transplantation

Keywords

T-cell lymphocyte allo-recognition; CNI-free immunosuppressive regimen; Enzyme-linked immunospot (ELISPOT)

Outcome Measures

Primary Outcomes (1)

• Percentage of biopsy-confirmed acute rejection episodes

  To describe cumulative biopsy-confirmed acute rejection in both groups by intention to treat analysis.

  6 months

Secondary Outcomes (13)

• Percentage of steroid-sensitive acute rejection episodes

  6 months

• Percentage of acute rejection episodes requiring treatment with antilymphocyte antibodies.

  6 months

• Renal function estimated by Modification of Diet in Renal Disease (MDRD) formula.

  12 months

• Proteinuria measured in g/day

  6 months

• Histology at month 6 protocol kidney allograft biopsy

  6 months

Study Arms (2)

A- negative pre-transplant ELISPOT

EXPERIMENTAL

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.

Drug: PRE-TRANSPLANT (PRE=before)

B- Positive pre-transplant ELISPOT

EXPERIMENTAL

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.

Drug: PRE-TRANSPLANT (PRE=before)

Interventions

PRE-TRANSPLANT (PRE=before) DRUG

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).

A- negative pre-transplant ELISPOT; B- Positive pre-transplant ELISPOT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of donor and recipient between 18 and 65 years.
• 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.
• Panel reactive antibody (PRA) ≤ 20%, with negative standard cross-match.
• Women of childbearing potential must have a negative serum pregnancy test before randomization.
• 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.
• Signed and dated informed consent prior to transplantation.

You may not qualify if:

• Multiple organ transplants
• Recipients of adult or pediatric en bloc kidney transplants or dual transplantation or non-heart beating donors.
• Evidence of active systemic or localized major infection.
• Evidence of infiltrate, cavitation, or consolidation on chest x-ray obtained during the screening/baseline evaluation.
• Use of any investigational drug or treatment up to 4 weeks prior to transplantation.
• 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.
• 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.
• Subjects with a screening/baseline total white blood cell count \< 2,000/mm3 or absolute neutrophil count (ANC) \< 500, platelet count \< 100,000/mm3.
• 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.
• History of malignancy within 2 years of enrollment (except for adequately treated basal cell or squamous cell carcinoma of the skin).
• Patient with psychiatric disorders that could be non-compliance for the treatment.
• Non Caucasian patients.
• Active peptic ulcers that could produce intestinal absorption disorders.
• 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).
• Diabetic patients.

Sponsors & Collaborators

• Josep M Grinyo: lead
• Carlos III Health Institute: collaborator

Study Sites (2)

Nephrology Department. Hospital Vall d'Hebró

Barcelona, Barcelona, 08035, Spain

Location

Nephrology Department. Hospital de Bellvitge

L'Hospitalet de Llobregat, Barcelone, 08907, Spain

Location

Related Publications (3)

• Bestard O, Cruzado JM, Mestre M, Caldes A, Bas J, Carrera M, Torras J, Rama I, Moreso F, Seron D, Grinyo JM. Achieving donor-specific hyporesponsiveness is associated with FOXP3+ regulatory T cell recruitment in human renal allograft infiltrates. J Immunol. 2007 Oct 1;179(7):4901-9. doi: 10.4049/jimmunol.179.7.4901.

  PMID: 17878390 BACKGROUND

• Bestard O, Crespo E, Stein M, Lucia M, Roelen DL, de Vaal YJ, Hernandez-Fuentes MP, Chatenoud L, Wood KJ, Claas FH, Cruzado JM, Grinyo JM, Volk HD, Reinke P. Cross-validation of IFN-gamma Elispot assay for measuring alloreactive memory/effector T cell responses in renal transplant recipients. Am J Transplant. 2013 Jul;13(7):1880-90. doi: 10.1111/ajt.12285. Epub 2013 Jun 13.

  PMID: 23763435 BACKGROUND

• Bestard O, Cruzado JM, Lucia M, Crespo E, Casis L, Sawitzki B, Vogt K, Cantarell C, Torras J, Melilli E, Mast R, Martinez-Castelao A, Goma M, Reinke P, Volk HD, Grinyo JM. Prospective assessment of antidonor cellular alloreactivity is a tool for guidance of immunosuppression in kidney transplantation. Kidney Int. 2013 Dec;84(6):1226-36. doi: 10.1038/ki.2013.236. Epub 2013 Jun 19.

  PMID: 23783240 RESULT

Related Links

• This is the center in Spain for the central contact and the main location including patients.

Study Officials

• Josep M Grinyó, PhD MD

  Nephrology Department. Hospital de Bellvitge. Spain

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief of the Nephrology Department- Hospital Universitari de Bellvitge

Study Record Dates

• First Submitted: April 19, 2010
• First Posted: September 6, 2010
• Study Start: March 1, 2008
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2013
• Last Updated: February 25, 2014

Record last verified: 2014-02

Locations

ES (2)