REmoval Of Tacrolimus For Sirolimus Following Thymoglobulin Induction On The Development of REgulatory T Cells in Kidney Transplant Patients

Phase 4

• Conditions: Development of circulating regulatory T cells; Kidney transplant function, complications and biopsy; Cardiovascular health; Metabolic outcomes (glucose abnormality); Clinical significant infections and cancers; Blood - Other blood disorders; Renal and Urogenital - Kidney disease; Cardiovascular - Other cardiovascular diseases

• Registration Number: ACTRN12611001224910
• Lead Sponsor: Department of Health

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-11-29
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: ot yet recruiting
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Inclusion criteria at randomisation:
1.Males and females aged >18 years inclusive.
2.Primary and subsequent DCD renal transplant recipients.
3.Females capable of becoming pregnant must have a negative serum pregnancy test within 7 days prior to or at screening, and are required to practice a medically accepted effective method of birth control for the duration of the study and for a period of 6 weeks following discontinuation of study medication, even where there has been a history of infertility.
4.Patients who are willing and able to participate in the study and from whom written informed consent has been obtained.

Inclusion criteria for conversion:

1.Day 90-135 post-kidney transplantation.
2.Continuously maintained on Tacrolimus and Mycophenolic acid during the last 30 days.

Exclusion Criteria

Exclusion Criteria at randomisation:
1.Patients who are recipients of multiple organ transplants, kidney and pancreas, or previous transplant with any organ other than kidney but recipients receiving two kidneys from DCD donor can be included in study.
2.Patients at high immunological risk of graft loss, indicated by the presence of donor-specific antibody or loss of a previous renal allograft within the first 6 months of transplantation due to acute rejection.
3.Presence of any severe allergy or hypersensitivity to drugs similar to sirolimus (e.g. macrolides), tacrolimus, thymoglobulin, basiliximab or mycophenolic acid.
4.Patients who are recipients of A-B-O incompatible transplants or T or B cell allogeneic cross-match positive transplants.
5.Patients who are known to have chronic active Hepatitis C, or who are HIV or Hepatitis B surface antigen positive. Laboratory results obtained within 6 months prior to randomization are acceptable. Recipients of organs from donors who test positive for Hepatitis B surface antigen or Hepatitis C are excluded.
6.Patients with symptoms of significant somatic or mental illness, or inability to co-operate or communicate with the investigator.
7.Unresolved history of drug or alcohol abuse.
8.Patients with clinically significant infections requiring continued therapy, severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus that in the opinion of the investigator would interfere with the appropriate conduct of the study.
9.Patients with a history of malignancy within 3 years of transplant (other than excised basal cell carcinoma of the skin).
10.Breastfeeding women.
11.Abnormal physical or laboratory findings of clinical significance, which at investigator discretion would interfere with the objectives of the study.
12.Patients receiving drugs known to interact with tacrolimus and/or sirolimus, where exposure to the interacting drug is unstable/variable or may lead to difficulties attaining stable target levels of tacrolimus or sirolimus.

Exclusion Criteria at conversion:

1.3-month biopsy demonstrating subclinical/grade I rejection, recurrent glomerular disease and/or transplant glomerulopathy (patients with subclinical rejection or with grade I rejection may still be included provided they have a normal repeat biopsy within the conversion period. The repeat biopsy should occur at least 14 days after the last dose of methylprednisolone and at least 7 days prior to the conversion to sirolimus).

2.Any vascular or antibody-mediated or = grade 2 rejection according to Banff criteria at any time prior to conversion.

3.Patients treated with other immunosuppressive agents not described in this protocol (e.g. cyclosporine, everolimus).
4.Significant proteinuria (defined as equivalent to protein/creatinine ratio >80mg/mmol) within 1 week prior to randomization.
5.eGFR (4-point MDRD) of <35ml/min.
6.Patients with thrombocytopenia (platelets <75,000/mm3), with an absolute neutrophil count of <1,500/mm3 or leucopenia (leucocytes <2,500/mm3), or hemoglobin <8g/dL.
7.Evidence of severe liver disease (including abnormal liver enzyme profile, i.e. AST, ALT or total bilirubin >3 times ULN).
8.Patients with fasting total cholesterol >8mmol/L and/or triglyceride >4.5mmol/L despite lipid-lowering agents.
9.Recent major surgery within 2 weeks prior to conversion to sirolimus.

Study & Design

• Study Type: Interventional
• Study Design: Not specified