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Am J Nephrol. 2018;48(4):260-268. doi: 10.1159/000493551. Epub 2018 Oct 10.

Randomized Trial Comparing Proactive, High-Dose versus Reactive, Low-Dose Intravenous Iron Supplementation in Hemodialysis (PIVOTAL): Study Design and Baseline Data.

Author information

1
Department of Renal Medicine, King's College Hospital, Denmark Hill, London, United Kingdom.
2
Division of Cardiology and Metabolism, Department of Cardiology (CVK), and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) Partner Site Berlin, Charité Universitätsmedizin Berlin, Berlin, Germany.
3
Hull and East Yorkshire Hospitals and Hull York Medical School, Hull, United Kingdom.
4
Lister Hospital, Stevenage, United Kingdom.
5
University of Hertfordshire, Hertfordshire, United Kingdom.
6
Salford Royal Hospital, Salford, United Kingdom.
7
British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
8
Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom.
9
UK Renal Registry, Southmead Hospital, Bristol, United Kingdom.
10
Freeman Hospital, Newcastle upon Tyne, United Kingdom.
11
University College London, London, United Kingdom.
12
Oxford Kidney Unit, The Churchill, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.

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.

KEYWORDS:

Anemia; Chronic kidney disease; Hemodialysis; Intravenous iron; Iron sucrose

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