Correction of Anaemia and Progression of Renal Failure on Transplanted Patients
Condition: Anaemia; Renal Transplantation; Kidney Failure
MeSH terms: Renal Insufficiency; Anemia
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to evaluate, on renal transplanted patients with CGD, the effect
      of two levels of haemoglobin on quality of life at 6 months and the speed of progression of
      renal function degradation at 24 months.

      This study will recruit 140 patients in 21 centers in France.
    

Detailed description: 
      The number of patients arriving each year at the stage of final renal insufficiency (IRT) and
      requiring the dialysis of substitution does not cease growing, in parallel with continuous
      ageing of the population in industrialized countries. The incidence of the IRT is
      approximately 110 new patients per million inhabitants per year, which represents an annual
      progression from approximately 4% to 8% according to areas.Approximately 35000 patients are
      currently treated by dialysis, 90% by hemodialysis and 10% per peritoneal dialysis . The
      other alternative to the treatment of the IRT is renal transplantation. Approximately 2000
      patients are transplanted each year in France, and it is estimated that a minimum of 3000
      transplantations should annually be carried out in order to answer at the request of the
      patients registers on a chronic program of dialysis and in to be transplanted age.

      The total number of patients living with a functional graft is approximately 15000.

      The IRT is a major problem of public health and its cost is considerable: for less than 50000
      patients, this one represents nearly 4% of the annual budget of the social security. To slow
      down the progression of the IRC represents a major therapeutic challenge, including at the
      transplanted patients.

      The physiopathological mechanisms proposed to explain the harmful role of anaemia in the
      progression of the renal lesions during the IRC rest on the tissue hypoxia induced by the
      reduction in haemoglobin. The tissue hypoxia supports the development of the interstitial
      fibrosis by stimulating the production of type I collagen and some inhibitors of
      metalloproteases, implied in the extracellular matrix degradation. The hypoxia also
      stimulates the synthesis of TGF-beta, pro-fibrosing factors implied in the progression of
      many renal diseases, in particular the nephropathy diabetic. By reducing the hypoxia thanks
      to the correction of anaemia by the EPO, one can hope to slow down the progression of the
      interstitial fibrosis, and thus the progression of the renal insufficiency. Lastly, the
      correction of anaemia reduces resistance to insulin and the secondary hyperinsulinism to
      uraemia, improves the dyslipidemia and the oxidizing stress, factors also implied in the
      progression of many nephropathies, diabetic or not.

      It appears that anaemia is a factor of risk of progression of the chronic nephropathies. To
      slow down the progression of the chronic dysfunction of the graft is an important challenge
      because of shortage of graft and impossibility, in the current state of the French centers of
      renal transplantation to carry out the number of necessary grafts to provide for the current
      waiting list. Our hypothesis, if it is checked, should make it possible to very appreciably
      improve the quality of life of the transplanted patients and to slow down the progression of
      their IRC, thus delaying the duration before return in dialysis.

      Population: Renal patients transplanted since at least 12 months, presenting a CGD defined by
      20 ml/mn/1,73 m2 > Clcr < 50 ml/mn/1,73 m2 and an anaemia (Hb < 11,5 g/dl)

      The patients answering the criteria of selection will be assigned by randomization with the
      one of the two following groups:

        -  Group a: target haemoglobin: 13 to 15 g/dl

        -  Group b: target haemoglobin: 10,5 to 11,5 g/dl

      Criteria of inclusion

        -  Adults of male or female sex of more than 18 years

        -  Patients having profited from one 1st or one the 2nd renal Transplantation

        -  Patients Transplanted since more than 1 year

        -  Patients having a CGD defined by Clcr < 50 ml/mn/1,73 m2

        -  Patients presenting an anaemia: Hb lower than 11,5 g/dl

        -  Absence of deficiency out of iron

        -  Patients having given their in writing consent

      Study Treatment: Neorecormon® (Epoétine beta) under cutaneous injection

      The objective of the study is to show a difference between group A "haemoglobin target: 13 to
      15 g/dl" and group it B "haemoglobin target: 10,5 to 11,5 g/dl", with regard to the renal
      function.

      The calculation of the number of patients is thus based on a model of covariance analysis in
      repeated measurements of clearance of creatinin on the whole of the times evaluated between
      J0 and M24 and on the following hypothesis:

        -  H0: no effect groups during the two years of follow-up

        -  H1: Effect groups, evolution different from the values of Clcr during the follow-up

      The alfa-risk (probability of rejecting H0 wrongly) was fixed at 5% The beta-risk
      (probability of keeping H0 wrongly) at 10% The total number of patients to be randomized was
      estimated at 140 (70 by group) This number of patients will also make it possible to test the
      scores of quality of life with a power higher than 90%
    

Intervention name(s): Neorecormon
Intervention type(s): Drug
Intervention description(s): Administration SC one a week in patients randomized in group A Administration SC if Hb below 10.5 g/dl in group B
Other intervention name(s): Epoetin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: anaemia; renal transplantation; kidney failure