Tacrolimus After rATG and Infliximab Induction Immunosuppression (RIMINI)
Condition: Renal Transplant Rejection
Study type: Interventional
Phase: Phase 2

Summary: 
      International multicenter open-label single-arm confidence-interval-estimation based Phase II
      clinical trial, aiming to estimate a plausible range of the proportion of patients
      experiencing efficacy failure in the population, to provide evidence for efficacy and safety
      of the induction regimen with rATG and infliximab and a go/no go rule for further clinical
      development.
    

Detailed description: 
      A total of 75 patients will receive the proposed induction regimen, with expected 68
      completers accounting for drop-outs and non-compliances with the protocol. If up to 27 out of
      the 68 completers experience efficacy failure, a progression into a larger trial will be
      considered justifiable. If the number of patients experiencing efficacy failure is between 28
      and 34 out of 68, the merits of a larger non-inferiority design will be considered depending
      on the risk/benefit assessment. If more than 34 out of the 68 completers experience efficacy
      failure, a progression into a larger trial would be considered unjustifiable. 1st kidney
      transplant recipients (low risk: PRA/cPRA < 20%, no DSA) will receive short rATG induction
      (2x1.5 mg/kg) given perioperatively and on first postoperative day. All patients will receive
      one shot Infliximab mAb at day 2. Since POD1, maintenance IS consists of Tac and tapered
      steroids therapy. All patients will be followed up for one year.

      At the POD 0 the first rATG dose (1.5mg/kg) will be given according to the local practice and
      Methyprednisolon 500mg will be given before reperfusion. At the POD 1 patients will receive
      methylprednisolon 500mg i.v. followed by second rATG dose (1.5mg/kg). Infliximab 5mg/kg b.w.
      will be given in slow infusion on POD2. Tacrolimus will be given the first dose before
      surgery at dose 0.1 mg/kg and next from POD1 at 0.2mg/kg/day and doses adjusted according to
      blood trough levels (10-15 ng/mL, POD1-POD13, 5-8ng/mL POD 14-90, 4-6ng/mL POD >90. Prednison
      (or appropriate dose of methylprednisolone) will be initiated POD 2 at a dose of 20mg/day and
      slowly tapered down to 5 mg at the POD 7 (POD2: 20mg, POD3: 15mg, POD4-5: 10mg, POD6-7:
      7,5mg, > POD7: 5mg).
    

Intervention name(s): Antithymocyte Immunoglobulin (Rabbit)
Intervention type(s): Drug
Intervention description(s): 1st kidney transplant recipients (low risk: PRA/cPRA < 20%, no DSA) will receive short rATG induction (2x1.5 mg/kg) given perioperatively and on first postoperative day. All patients will receive one shot Infliximab mAb at day 2. Since POD1, maintenance IS consists of Tac and tapered steroids therapy.
Other intervention name(s): Infliximab; Tacrolimus; Prednisolone
Intervention MeSH terms: Prednisolone; Infliximab; Tacrolimus; Thymoglobulin; Antilymphocyte Serum; Immunoglobulins; Immunoglobulins, Intravenous; Antibodies
Intervention model: Single Group Assignment
Intervention model description: This is a confidence-interval-estimation based early phase design, aiming to estimate a plausible range of the population treatment effect which is not bound to a formal hypothesis.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: transplant medicine