David W Johnson1, Elaine M Pascoe2, Sunil V Badve3, Kim Dalziel4, Alan Cass5, Philip Clarke4, Paolo Ferrari6, Stephen P McDonald7, Alicia T Morrish2, Eugenie Pedagogos8, Vlado Perkovic9, Donna Reidlinger2, Anish Scaria2, Rowan Walker10, Liza A Vergara2, Carmel M Hawley3. 1. Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia; Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia; Translational Research Institute, Brisbane, Australia. Electronic address: david.johnson2@health.qld.gov.au. 2. Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia. 3. Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia; Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia. 4. Center for Health Policy, Programs & Economics, University of Melbourne, Melbourne, Australia. 5. Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia; Menzies School of Health Research, Darwin, Australia. 6. Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia; Department of Renal Medicine, Fremantle Hospital, Fremantle, Australia. 7. Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia; Department of Nephrology and Transplantation Services, University of Adelaide at Central Northern Adelaide Renal and Transplantation Services, Adelaide, Australia. 8. Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia; Department of Nephrology, Royal Melbourne Hospital, Melbourne, Australia. 9. Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia; George Institute, Sydney, Australia. 10. Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia; Department of Renal Medicine, The Alfred Hospital, Melbourne, Australia.
Abstract
BACKGROUND:Erythropoiesis-stimulating agent (ESA)-hyporesponsive anemia is common in chronic kidney disease (CKD). Pentoxifylline shows promise as a treatment for ESA-hyporesponsive anemia, but has not been rigorously evaluated. STUDY DESIGN: Multicenter, double-blind, randomized, controlled trial. SETTING & PARTICIPANTS: 53 adult patients with CKD stage 4 or 5 (including dialysis) and ESA-hyporesponsive anemia (hemoglobin≤120g/L and ESA resistance index [calculated as weight-adjusted weekly ESA dose in IU/kg/wk divided byhemoglobin concentration in g/L]≥1.0IU/kg/wk/g/L for erythropoietin-treated patients and ≥0.005μg/kg/wk/g/L for darbepoetin-treated patients). INTERVENTIONS:Pentoxifylline (400mg/d; n=26) or matching placebo (control; n=27) for 4 months. PRIMARY OUTCOME: ESA resistance index at 4 months; secondary outcomes: hemoglobin concentration, ESA dose, blood transfusion requirement, serum ferritin level and transferrin saturation, C-reactive protein level, adverse events, quality of life, and health economics. RESULTS: There was no statistically significant difference in ESA resistance index between the pentoxifylline and control groups (adjusted mean difference, -0.39 [95%CI, -0.89 to 0.10] IU/kg/wk/g/L; P=0.1). Pentoxifylline significantly increased hemoglobin concentration relative to the control group (adjusted mean difference, 7.6 [95%CI, 1.7-13.5] g/L; P=0.01). There was no difference in ESA dose between groups (-20.8 [95%CI, -67.2 to 25.7] IU/kg/wk; P=0.4). No differences in blood transfusion requirements, adverse events, or quality of life were observed between groups. Pentoxifylline cost A$88.05 (US $82.94) per person over the trial and produced mean savings in ESA cost of A$1,332 (US $1,255). The overall economic impact over the trial period was a saving of A$1,244 (US $1,172) per person for the pentoxifylline group compared with controls. LIMITATIONS: Sample size smaller than planned due to slow recruitment. CONCLUSIONS:Pentoxifylline did not significantly modify ESA hyporesponsiveness, but increased hemoglobin concentration. Further studies are warranted to determine whether pentoxifylline therapy represents a safe strategy for increasing hemoglobin levels in patients with CKD with ESA-hyporesponsive anemia. Crown
RCT Entities:
BACKGROUND: Erythropoiesis-stimulating agent (ESA)-hyporesponsive anemia is common in chronic kidney disease (CKD). Pentoxifylline shows promise as a treatment for ESA-hyporesponsive anemia, but has not been rigorously evaluated. STUDY DESIGN: Multicenter, double-blind, randomized, controlled trial. SETTING & PARTICIPANTS: 53 adult patients with CKD stage 4 or 5 (including dialysis) and ESA-hyporesponsive anemia (hemoglobin≤120g/L and ESA resistance index [calculated as weight-adjusted weekly ESA dose in IU/kg/wk divided by hemoglobin concentration in g/L]≥1.0IU/kg/wk/g/L for erythropoietin-treated patients and ≥0.005μg/kg/wk/g/L for darbepoetin-treated patients). INTERVENTIONS:Pentoxifylline (400mg/d; n=26) or matching placebo (control; n=27) for 4 months. PRIMARY OUTCOME: ESA resistance index at 4 months; secondary outcomes: hemoglobin concentration, ESA dose, blood transfusion requirement, serum ferritin level and transferrin saturation, C-reactive protein level, adverse events, quality of life, and health economics. RESULTS: There was no statistically significant difference in ESA resistance index between the pentoxifylline and control groups (adjusted mean difference, -0.39 [95%CI, -0.89 to 0.10] IU/kg/wk/g/L; P=0.1). Pentoxifylline significantly increased hemoglobin concentration relative to the control group (adjusted mean difference, 7.6 [95%CI, 1.7-13.5] g/L; P=0.01). There was no difference in ESA dose between groups (-20.8 [95%CI, -67.2 to 25.7] IU/kg/wk; P=0.4). No differences in blood transfusion requirements, adverse events, or quality of life were observed between groups. Pentoxifylline cost A$88.05 (US $82.94) per person over the trial and produced mean savings in ESA cost of A$1,332 (US $1,255). The overall economic impact over the trial period was a saving of A$1,244 (US $1,172) per person for the pentoxifylline group compared with controls. LIMITATIONS: Sample size smaller than planned due to slow recruitment. CONCLUSIONS:Pentoxifylline did not significantly modify ESA hyporesponsiveness, but increased hemoglobin concentration. Further studies are warranted to determine whether pentoxifylline therapy represents a safe strategy for increasing hemoglobin levels in patients with CKD with ESA-hyporesponsive anemia. Crown
Authors: Lei Zhang; Jeff Coombes; Elaine M Pascoe; Sunil V Badve; Kim Dalziel; Alan Cass; Philip Clarke; Paolo Ferrari; Stephen P McDonald; Alicia T Morrish; Eugenie Pedagogos; Vlado Perkovic; Donna Reidlinger; Anish Scaria; Rowan Walker; Liza A Vergara; Carmel M Hawley; David W Johnson Journal: Redox Rep Date: 2016-03-04 Impact factor: 4.412
Authors: Borut Cizman; Helen T Smith; Rodrigo Refoios Camejo; Linda Casillas; Harjeet Dhillon; Fan Mu; Eric Wu; Jipan Xie; Peter Zuckerman; Daniel Coyne Journal: Kidney Med Date: 2020-08-10
Authors: Valeria Saglimbene; Suetonia C Palmer; Jonathan C Craig; Marinella Ruospo; Antonio Nicolucci; Marcello Tonelli; David Johnson; Giuseppe Lucisano; Gabrielle Williams; Miriam Valentini; Daniela D'Alonzo; Fabio Pellegrini; Paolo Strippoli; Mario Salomone; Antonio Santoro; Stefano Maffei; Jörgen Hegbrant; Gianni Tognoni; Giovanni F M Strippoli Journal: PLoS One Date: 2017-03-01 Impact factor: 3.240
Authors: Sunil V Badve; Lei Zhang; Jeff S Coombes; Elaine M Pascoe; Alan Cass; Philip Clarke; Paolo Ferrari; Stephen P McDonald; Alicia T Morrish; Eugenie Pedagogos; Vlado Perkovic; Donna Reidlinger; Anish Scaria; Rowan Walker; Liza A Vergara; Carmel M Hawley; David W Johnson Journal: Can J Kidney Health Dis Date: 2015-08-18