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

Disorder Related to Renal Transplantation Clinical Trial

— SIRES  

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01195194
• Other study ID #: SIRES
• Secondary ID: 2007-002378-68
• Status: Completed
• Phase: Phase 4
• First received: April 19, 2010
• Last updated: February 24, 2014
• Start date: March 2008
• Est. completion date: June 2013

Study information

• Verified date: February 2014
• Source: Hospital Universitari de Bellvitge
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: June 2013
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Disorder Related to Renal Transplantation

Intervention

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).

Locations

Country	Name	City	State
Spain	Nephrology Department. Hospital Vall d'Hebró	Barcelona
Spain	Nephrology Department. Hospital de Bellvitge	L'Hospitalet de Llobregat	Barcelone

Sponsors (2)

Lead Sponsor	Collaborator
Josep M Grinyo	Carlos III Health Institute

Country where clinical trial is conducted

Spain, 

References & Publications (3)

Bestard O, Crespo E, Stein M, Lúcia M, Roelen DL, de Vaal YJ, Hernandez-Fuentes MP, Chatenoud L, Wood KJ, Claas FH, Cruzado JM, Grinyó JM, Volk HD, Reinke P. Cross-validation of IFN-? 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. — View Citation

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, Gomà M, Reinke P, Volk HD, Grinyó JM. Prospective assessment of antidonor cellular alloreactivity is a tool for guidance — View Citation

Bestard O, Cruzado JM, Mestre M, Caldés A, Bas J, Carrera M, Torras J, Rama I, Moreso F, Serón D, Grinyó 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of biopsy-confirmed acute rejection episodes	To describe cumulative biopsy-confirmed acute rejection in both groups by intention to treat analysis.	6 months	No
Secondary	Percentage of steroid-sensitive acute rejection episodes	To describe the percentage of steroid-sensitive acute rejections rejection in both groups by intention to treat analysis.	6 months	No
Secondary	Percentage of acute rejection episodes requiring treatment with antilymphocyte antibodies.	To describe the need for antibody treatment in acute rejection episodes in both groups by intention to treat analysis.	6 months	No
Secondary	Renal function estimated by Modification of Diet in Renal Disease (MDRD) formula.	To describe renal function measured by MDRD in both groups by intention to treat and "on therapy" analysis.	12 months	No
Secondary	Proteinuria measured in g/day	To describe proteinuria in g/day in both groups by intention to treat analysis.	6 months	No
Secondary	Histology at month 6 protocol kidney allograft biopsy	To describe histology at month 6 in both groups by intention to treat and "on therapy" analysis.	6 months	No
Secondary	Percentage of patients with negative ELISPOT	To describe percentage of patients with negative ELISPOT in both groups by intention to treat and "on therapy" analysis.	6 months	No
Secondary	Percentage of patients in group A requiring CNI introduction.	To describe the percentage of patients in group A requiring CNI introduction.	24 months	No
Secondary	Percentage of patients presenting adverse events requiring study withdrawal	To describe adverse events in the whole group ("screening failure" plus "intention to treat") in both treatments groups.	24 months	Yes
Secondary	Percentage of biopsy-confirmed acute rejection episodes	To describe cumulative biopsy-confirmed acute rejection in both groups by intention to treat analysis.	12 months	No
Secondary	Percentage of steroid-sensitive acute rejections rejection episodes	To describe the percentage of steroid-sensitive acute rejections rejection in both groups by intention to treat analysis.	12 months	No
Secondary	Percentage of acute rejection episodes requiring treatment with antilymphocyte antibodies	To describe the need for antibody treatment in acute rejection episodes in both groups by intention to treat analysis.	12 months	No
Secondary	Proteinuria measured in g/day	To describe proteinuria in g/day in both groups by intention to treat analysis.	12 months	No
Secondary	Percentage of patients with negative ELISPOT	To describe percentage of patients with negative ELISPOT in both groups by intention to treat and "on therapy" analysis.	12 months	No

External Links

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