Pentoxifylline in anaemia resistant to erythropoietin (PEAR) study A double blind placebo controlled randomised trial

Abstract

Background Hyporesponsiveness to erythropoiesis-stimulating agents (ESA) and its association with adverse cardiovascular outcomes remains a considerable problem in patients with end-stage renal disease (ESRD) undergoing haemodialysis. Pentoxifylline has been shown to have some beneficial effect on ESA Hyporesponsiveness by reducing inflammation in ESRD patients. Methods We conducted a single centre, double-blind, placebo-controlled randomised trial to study the effect of Pentoxifylline on Erythropoietin stimulating agent (ESA) requirement of stable haemodialysis patients. Inclusion criteria were equivalent ESA dose of greater than or equal to 6000 International Units (I.U) per week or ESA resistance index greater than or equal to 6.5 I.U /kg/wk/Hb (g/dl) and stable Hb between 9 to 12 g/dl. The primary study endpoint was ESA requirement relative to Haemoglobin (Hb) level at the end of study period of 6 months. Secondary endpoints included safety analysis, Hb values, ESA dose and cardiovascular imaging biomarkers such as vascular PET CT and cardiac MRI scan. Cytokine profile was also analysed during the study. Results A total of 69 patients underwent randomisation. At the end of the study period, there was no statistically significant (p value= 0.26) difference in ESA /Hb ratio between pentoxifylline and placebo group (Mean (SD) 3.98 mcg/gm/dl (3.09) versus 4.91 mcg/gm/dl (3.49) respectively). The secondary outcomes did not show any statistically significant change between pentoxifylline and placebo group. There were no concerns regarding the safety of pentoxifylline in haemodialysis patients. The cytokine profile showed a reduction in inflammatory cytokines titres and rise in anti-inflammatory cytokines in the entoxifylline group analysed as slopes of cytokine variability longitudinally. Conclusions Pentoxifylline did not improve the ESA requirement in ESA hyporesponsive, stable haemodialysis patients over six months period. There was no statistically significant change in cardiovascular imaging biomarkers between Pentoxifylline and placebo group. Cytokine profile showed a favourable response to Pentoxifylline therapy.