Efficacy of Pentoxifylline on Primary Nephrotic Syndrome
Condition: Nephrotic Syndrome
MeSH terms: Nephrotic Syndrome; Nephrosis; Syndrome
Study type: Interventional
Phase: Phase 3

Summary: 
      We aim to investigate (1) the effects of combined pentoxifylline and corticosteroids,
      compared to that of corticosteroids, on patients with primary nephrotic syndrome; and if
      possible (2) the effects of pentoxifylline monotherapy on patients with primary nephrotic
      syndrome not suitable for or intolerant of standard corticosteroid therapy.
    

Detailed description: 
      Pentoxifylline (PTX) is a phosphodiesterase inhibitor that is used clinically to treat
      patients with peripheral vascular disorders. In addition to its hemorheologic activity, PTX
      possesses potent anti-inflammatory and immunomodulatory properties. In vivo, PTX has shown
      its ability to attenuate nephrotic syndrome secondary to membranous glomerulonephritis and
      lupus nephritis, and to reduce subnephrotic proteinuria of early and advanced diabetic
      nephropathy. However, the anti-proteinuric effect of PTX has been traditionally attributed to
      down-regulation of tumor necrosis factor (TNF)-alpha. Whether or not other inflammatory
      mediators are also affected by PTX has never been studied. Our previous works have shown that
      PTX can inhibit cytokine or albumin-induced monocyte chemoattractant protein (MCP)-1
      production in vitro, and attenuate proteinuria in association with suppression of renal MCP-1
      messenger ribonucleic acid expression in experimental glomerulonephritis. More recently, we
      have found that PTX lowers proteinuria by modulating renal MCP-1 production in a subgroup of
      human glomerular diseases. In this study, we aim to investigate whether combination of PTX
      and corticosteroids results in additive reduction in proteinuria, and higher remission rates
      in patients with primary nephrotic syndrome. The secondary objective is to study whether PTX
      monotherapy can be effective in patients with primary nephrotic syndrome not suitable for or
      intolerant of corticosteroid therapy.

      This study is a prospective, open-labeled, comparative study including primary nephrotic
      patients randomized into 2 groups. Group A receives oral PTX plus oral prednisolone, whereas
      group B receives oral prednisolone alone. The active treatment duration is 1 year for both
      subgroups. The dose for PTX will be 1,200 mg/day (for estimated glomerular filtration rate
      (GFR) ≧60 ml/min) or 800 mg/day (estimated GFR 59-30 ml/min) x 6 months, followed by stepwise
      reduction (800 mg/day x 6 M, 400 mg/day x 6 M and discontinued at 18 M). The dose for
      prednisolone will be 1 mg/kg/day for the initial 3 months, then the dose will be gradually
      tapered, thus by 6 months the dose will be 0.5 mg/kg/day, and at 12 months the dose will be
      reduced to around 5-10 mg/day, and discontinued at 18 M. For patients not considered suitable
      for (eg., active chronic hepatitis B virus or hepatitis C virus infection), or intolerance of
      (eg., concomitant diabetes mellitus, active peptic ulcer disease) standard corticosteroid
      therapy, PTX 1,200 mg/day will be administered to them for a total of 1 year. Serum and urine
      specimens will be collected before initiation of therapy (day 0), and at month 1, 3, 6, and
      12 after the commencement of therapy. GFR will be calculated by Cockcroft-Gault and
      simplified Modification of Diet in Renal Disease (MDRD) formula. Urinary protein excretion
      will be quantitated by spot urine protein/creatinine ratio. All biochemical and immunological
      analyses will be performed by the Department of Laboratory Medicine, National Taiwan
      University Hospital. Serum and urine samples will be measured for inflammatory mediators and
      podocyte markers by using commercial ELISA kits.
    

Intervention name(s): pentoxifylline; Corticosteroid
Intervention type(s): Drug; Drug
Intervention description(s): Oral pentoxifylline 1,200 mg/day (for estimated GFR ≧60 ml/min) or 800 mg/day (estimated GFR 59-30 ml/min) x 6 months, followed by stepwise reduction (800 mg/day x 6 M, 400 mg/day x 6 M and discontinued at 18 M; Oral prednisolone (1 mg/kg/day) x 3 M, followed by gradual tapering (0.5 mg/kg/day at 6 M, 0.25 mg/day at 12 M, and discontinued at 18 M
Other intervention name(s): Trental; Predonin
Intervention MeSH terms: Pentoxifylline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: nephrotic syndrome, pentoxifylline, corticosteroid