Trial of Steroid Avoidance and Low-dose CNI by ATG-induction in Renal Transplantation (SAILOR)

Vastra Gotaland Region

Status and phase: Completed; Phase 4

Conditions: Diabetes Mellitus

Treatments: Drug: Steroid-free low TAC-arm: Thymoglobulin Standard low-TAC arm: Simulect, prednisolon

Study type: Interventional

Funder types: Other

Identifiers

NCT02083991

2012-000451-13

Details and patient eligibility

About

Balancing immunosuppressive treatment in organ transplantation in order to achieve effective prevention of rejection on one side and avoidance of negative side effects on the other side is a major challenge, leading to developing different immunosuppressive protocols. Cornerstones of immunosuppressive treatment such as Corticosteroids (CS) and Calcineurin Inhibitors (CNI) are known to cause an increased incidence of diabetes, cardiovascular morbidity, nephrotoxicity and malignancies.

The investigators believe that both avoidance of CS and minimization of CNI, while using Anti-ThymocyteGlobuline(ATG) induction (instead of interleucin-2 receptor blockers) and mycofenolate mofetil(MMF) therapeutic drug monitoring is going to reduce negative side effects, without increased rejection frequency in renal transplanted patients.

Enrollment: 224 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• First or second single kidney (cadaveric or living donors) transplant recipients.
• Considered for a standard immunosuppressive protocol.
• Must be capable of giving written informed connect for participation in the study for 24 months.

Exclusion criteria

• Diabetes mellitus or plasma glucose >11,1 at admission.
• Receiving steroids at the time of transplantation or likely to need steroids after transplantation.
• Multiorgan transplants and/or previously transplanted with any other organ than kidney.
• Panel reacting antibodies(PRA) >25% in most recent test or considered to be of high risk for rejection which requires an enhanced immunosuppression.
• Renal transplants from HLA-identical sibling.
• Hypersensitivity to, or disability to take immunosuppressive drugs.
• Blood group(ABO)-incompatible transplants.
• Unlikely to comply with the study requirements.
• Transplant from donor positive for HIV, HBsAg, Hepatitis C.
• Female of childbearing potential planing/being pregnant or unwilling to use contraception.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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224 participants in 2 patient groups

Steroid-free low TAC-arm

Experimental group

Description:

Induction therapy: Thymoglobulin i.v. 2,5 mg/kg day 0 and 1, preceded by methylprednisolone i.v. 250 mg day 0 and 50 mg day 1. Maintenance therapy: Advagraf(TAC) 0,2 mg/kg p.o. started day1 (target concentration 5-10 ng/ml, after 3 months 4-7 ng/ml; MMF 1g x 2 p.o. (target Area Under Curve, AUC 40-60 mg.h/L); No steroids p.o.

Treatment:

Drug: Steroid-free low TAC-arm: Thymoglobulin Standard low-TAC arm: Simulect, prednisolon

Standard low-TAC arm

Active Comparator group

Description:

Induction therapy: Simulect i.v. 20 mg day 0 and 4; Steroids i.v. according to local practice. Maintenance therapy: Advagraf(TAC) p.o. 0,2 mg/(target concentration 5-10 ng/ml, after 3 months 4-7 ng/ml); MMF 1g x 2 p.o. (target AUC 40-60 mg.h/L); Steroids p.o. according to hospital practice (but not less than 5mg daily after 6 months).

Treatment:

Drug: Steroid-free low TAC-arm: Thymoglobulin Standard low-TAC arm: Simulect, prednisolon