A randomized, placebo-controlled trial of pentoxifylline on erythropoiesis-stimulating agent hyporesponsiveness in anemic patients with CKD: The handling erythropoietin resistance with oxpentifylline (HERO) trial

HERO Study Collaborative Group, David W. Johnson, Elaine M. Pascoe, Sunil V. Badve, Kim Dalziel, Alan Cass, Philip Clarke, Paolo Ferrari, Alicia T. Morrish, Stephen McDonald, Vlado Perkovic, Donna Reidlinger, Anish Scaria, Rowan Walker, Liza A. Vergara, Carmel M. Hawley, Emmanuel D'Almeida, Rob Fassett, Carl Kirkpatrick, Richard Phoon & 29 others Andrew Tonkin, Andrew Forbes, Adeera Levin, David C. Wheeler, Meg Jardine, Jenny Burman, Samantha Hand, Leanne Garvey, Michael Suranyi, Margaret Gilbert, Zoltan Endre, Katheen McNamara, Paul Snelling, Kumar Mahadevan, Andrea Pollock, Diana Leary, Sharad Ratanjee, Julie Kirby, Rajiv Juneja, Kathy Hill, Natasha Cook, Pascal Bisscheroux, Lawrence McMahon, Annette Kent, Matija Raspudic, Uli Steinwandel, Sharan Dogra, Susan Pellicano, Peta Anne Paul-Brent

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 ≤ 120 g/L and ESA resistance index [calculated as weight-adjusted weekly ESA dose in IU/kg/wk divided by hemoglobin concentration in g/L] ≥ 1.0 IU/kg/wk/g/L for erythropoietin-treated patients and ≥0.005 μg/kg/wk/g/L for darbepoetin-treated patients). Interventions: Pentoxifylline (400 mg/d; n 5 26) or matching placebo (control; n 5 27) for 4 months. Outcomes: 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, 20.39 [95% CI, 20.89 to 0.10] IU/kg/wk/g/L; P 5 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 5 0.01). There was no difference in ESA dose between groups (220.8 [95% CI, 267.2 to 25.7] IU/kg/wk; P 5 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.

LanguageEnglish
Pages49-57
Number of pages9
JournalAmerican Journal of Kidney Diseases
Volume65
Issue number1
DOIs
Publication statusPublished - 1 Jan 2015

ASJC Scopus subject areas

  • Nephrology

Cite this

@article{e57e72024bac4eb3957e8e178bfc2e05,
title = "A randomized, placebo-controlled trial of pentoxifylline on erythropoiesis-stimulating agent hyporesponsiveness in anemic patients with CKD: The handling erythropoietin resistance with oxpentifylline (HERO) trial",
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 ≤ 120 g/L and ESA resistance index [calculated as weight-adjusted weekly ESA dose in IU/kg/wk divided by hemoglobin concentration in g/L] ≥ 1.0 IU/kg/wk/g/L for erythropoietin-treated patients and ≥0.005 μg/kg/wk/g/L for darbepoetin-treated patients). Interventions: Pentoxifylline (400 mg/d; n 5 26) or matching placebo (control; n 5 27) for 4 months. Outcomes: 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, 20.39 [95{\%} CI, 20.89 to 0.10] IU/kg/wk/g/L; P 5 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 5 0.01). There was no difference in ESA dose between groups (220.8 [95{\%} CI, 267.2 to 25.7] IU/kg/wk; P 5 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.",
author = "{HERO Study Collaborative Group} and Johnson, {David W.} and Pascoe, {Elaine M.} and Badve, {Sunil V.} and Kim Dalziel and Alan Cass and Philip Clarke and Paolo Ferrari and Morrish, {Alicia T.} and Stephen McDonald and Vlado Perkovic and Donna Reidlinger and Anish Scaria and Rowan Walker and Vergara, {Liza A.} and Hawley, {Carmel M.} and Emmanuel D'Almeida and Rob Fassett and Carl Kirkpatrick and Richard Phoon and Andrew Tonkin and Andrew Forbes and Adeera Levin and Wheeler, {David C.} and Meg Jardine and Jenny Burman and Samantha Hand and Leanne Garvey and Michael Suranyi and Margaret Gilbert and Zoltan Endre and Katheen McNamara and Paul Snelling and Kumar Mahadevan and Andrea Pollock and Diana Leary and Sharad Ratanjee and Julie Kirby and Rajiv Juneja and Kathy Hill and Natasha Cook and Pascal Bisscheroux and Lawrence McMahon and Annette Kent and Matija Raspudic and Uli Steinwandel and Sharan Dogra and Susan Pellicano and Paul-Brent, {Peta Anne}",
year = "2015",
month = "1",
day = "1",
doi = "10.1053/j.ajkd.2014.06.020",
language = "English",
volume = "65",
pages = "49--57",
journal = "American Journal of Kidney Diseases",
issn = "0272-6386",
publisher = "W.B. Saunders Ltd",
number = "1",

}

TY - JOUR

T1 - A randomized, placebo-controlled trial of pentoxifylline on erythropoiesis-stimulating agent hyporesponsiveness in anemic patients with CKD

T2 - American Journal of Kidney Diseases

AU - HERO Study Collaborative Group

AU - Johnson, David W.

AU - Pascoe, Elaine M.

AU - Badve, Sunil V.

AU - Dalziel, Kim

AU - Cass, Alan

AU - Clarke, Philip

AU - Ferrari, Paolo

AU - Morrish, Alicia T.

AU - McDonald, Stephen

AU - Perkovic, Vlado

AU - Reidlinger, Donna

AU - Scaria, Anish

AU - Walker, Rowan

AU - Vergara, Liza A.

AU - Hawley, Carmel M.

AU - D'Almeida, Emmanuel

AU - Fassett, Rob

AU - Kirkpatrick, Carl

AU - Phoon, Richard

AU - Tonkin, Andrew

AU - Forbes, Andrew

AU - Levin, Adeera

AU - Wheeler, David C.

AU - Jardine, Meg

AU - Burman, Jenny

AU - Hand, Samantha

AU - Garvey, Leanne

AU - Suranyi, Michael

AU - Gilbert, Margaret

AU - Endre, Zoltan

AU - McNamara, Katheen

AU - Snelling, Paul

AU - Mahadevan, Kumar

AU - Pollock, Andrea

AU - Leary, Diana

AU - Ratanjee, Sharad

AU - Kirby, Julie

AU - Juneja, Rajiv

AU - Hill, Kathy

AU - Cook, Natasha

AU - Bisscheroux, Pascal

AU - McMahon, Lawrence

AU - Kent, Annette

AU - Raspudic, Matija

AU - Steinwandel, Uli

AU - Dogra, Sharan

AU - Pellicano, Susan

AU - Paul-Brent, Peta Anne

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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 ≤ 120 g/L and ESA resistance index [calculated as weight-adjusted weekly ESA dose in IU/kg/wk divided by hemoglobin concentration in g/L] ≥ 1.0 IU/kg/wk/g/L for erythropoietin-treated patients and ≥0.005 μg/kg/wk/g/L for darbepoetin-treated patients). Interventions: Pentoxifylline (400 mg/d; n 5 26) or matching placebo (control; n 5 27) for 4 months. Outcomes: 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, 20.39 [95% CI, 20.89 to 0.10] IU/kg/wk/g/L; P 5 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 5 0.01). There was no difference in ESA dose between groups (220.8 [95% CI, 267.2 to 25.7] IU/kg/wk; P 5 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.

AB - 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 ≤ 120 g/L and ESA resistance index [calculated as weight-adjusted weekly ESA dose in IU/kg/wk divided by hemoglobin concentration in g/L] ≥ 1.0 IU/kg/wk/g/L for erythropoietin-treated patients and ≥0.005 μg/kg/wk/g/L for darbepoetin-treated patients). Interventions: Pentoxifylline (400 mg/d; n 5 26) or matching placebo (control; n 5 27) for 4 months. Outcomes: 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, 20.39 [95% CI, 20.89 to 0.10] IU/kg/wk/g/L; P 5 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 5 0.01). There was no difference in ESA dose between groups (220.8 [95% CI, 267.2 to 25.7] IU/kg/wk; P 5 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.

UR - http://www.scopus.com/inward/record.url?scp=84922433423&partnerID=8YFLogxK

U2 - 10.1053/j.ajkd.2014.06.020

DO - 10.1053/j.ajkd.2014.06.020

M3 - Article

VL - 65

SP - 49

EP - 57

JO - American Journal of Kidney Diseases

JF - American Journal of Kidney Diseases

SN - 0272-6386

IS - 1

ER -