Randomized trial comparing proactive, high-dose versus reactive, low-dose intravenous iron supplementation in hemodialysis (PIVOTAL): study design and baseline data

Macdougall, I. C. et al. (2018) Randomized trial comparing proactive, high-dose versus reactive, low-dose intravenous iron supplementation in hemodialysis (PIVOTAL): study design and baseline data. American Journal of Nephrology, 48(4), pp. 260-268. (doi: 10.1159/000493551) (PMID:30304714)

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Abstract

Background: Intravenous (IV) iron supplementation is a standard maintenance treatment for hemodialysis (HD) patients, but the optimum dosing regimen is unknown. Methods: PIVOTAL (Proactive IV irOn Therapy in hemodiALysis patients) is a multicenter, open-label, blinded endpoint, randomized controlled (PROBE) trial. Incident HD adults with a serum ferritin < 400 µg/L and transferrin saturation (TSAT) levels < 30% receiving erythropoiesis-stimulating agents (ESA) were eligible. Enrolled patients were randomized to a proactive, high-dose IV iron arm (iron sucrose 400 mg/month unless ferritin > 700 µg/L and/or TSAT ≥40%) or a reactive, low-dose IV iron arm (iron sucrose administered if ferritin <200 µg/L or TSAT < 20%). We hypothesized that proactive, high-dose IV iron would be noninferior to reactive, low-dose IV iron for the primary outcome of first occurrence of nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure or death from any cause. If noninferiority is confirmed with a noninferiority limit of 1.25 for the hazard ratio of the proactive strategy relative to the reactive strategy, a test for superiority will be carried out. Secondary outcomes include infection-related endpoints, ESA dose requirements, and quality-of-life measures. As an event-driven trial, the study will continue until at least 631 primary outcome events have accrued, but the expected duration of follow-up is 2–4 years. Results: Of the 2,589 patients screened across 50 UK sites, 2,141 (83%) were randomized. At baseline, 65.3% were male, the median age was 65 years, and 79% were white. According to eligibility criteria, all patients were on ESA at screening. Prior stroke and MI were present in 8 and 9% of the cohort, respectively, and 44% of patients had diabetes at baseline. Baseline data for the randomized cohort were generally concordant with recent data from the UK Renal Registry. Conclusions: PIVOTAL will provide important information about the optimum dosing of IV iron in HD patients representative of usual clinical practice. Trial Registration: EudraCT number: 2013-002267-25.

Item Type:Articles
Additional Information:The PIVOTAL trial is funded by Kidney Research UK, which is supported by an unrestricted grant from Vifor Fresenius Medical Care Renal Pharma Ltd.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Murray, Mrs Heather and Ford, Professor Ian and McMurray, Professor John
Authors: Macdougall, I. C., White, C., Anker, S. D., Bhandari, S., Farrington, K., Kalra, P. A., McMurray, J. J.V., Murray, H., Steenkamp, R., Tomson, C. R.V., Wheeler, D. C., Winearls, C. G., and Ford, I.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:American Journal of Nephrology
Publisher:Karger Publishers
ISSN:0250-8095
ISSN (Online):1421-9670
Published Online:10 October 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in American Journal of Nephrology 48(4): 260-268
Publisher Policy:Reproduced under a Creative Commons License

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