Abstract: FR-OR143
High-Dose Versus Low-Dose Intravenous Iron Therapy in Hemodialysis: The PIVOTAL Trial
Session Information
- High-Impact Clinical Trials
October 26, 2018 | Location: 20A, San Diego Convention Center
Abstract Time: 10:45 AM - 11:00 AM
Category: Anemia and Iron Metabolism
- No subcategory defined
Authors
- Macdougall, Iain C., King's College Hospital, London, United Kingdom
- White, Claire, King's College Hospital, London, United Kingdom
- Anker, Stefan D., Charité Medical School, Berlin, Germany
- Bhandari, Sunil, Hull and East Yorkshire Hospitals NHS Trust and Hull York Medical School, East Yorkshire, Hull, United Kingdom
- Farrington, Ken, Lister Renal Unit, Hitchin, United Kingdom
- Kalra, Philip A., Salford Royal Hospital NHS Trust, Salford, United Kingdom
- McMurray, John, University of Glasgow, Glasgow, United Kingdom
- Murray, Heather M., University of Glasgow, Glasgow, United Kingdom
- Tomson, Charles, Freeman Hospital, Newcastle upon Tyne, United Kingdom
- Wheeler, David C., University College London, London, LONDON, United Kingdom
- Winearls, Christopher G., The Churchill Oxford Radcliff Hospital, Oxford, United Kingdom
- Ford, Ian, University of Glasgow, Glasgow, United Kingdom
Group or Team Name
- on behalf of the PIVOTAL Study Group
Background
Intravenous (IV) iron is widely used in the management of anemia in hemodialysis (HD) patients, but very little scientific evidence guides its appropriate use. The Proactive IV irOn Therapy in haemodiALysis patients (PIVOTAL) trial (EudraCT 2013-002267-25) was designed to compare the effects of 2 distinct IV iron dosing regimens on “hard” clinical outcomes, including mortality and cardiovascular (CV) events, as well as infection risk among HD patients.
Methods
In this multicenter, open-label, blinded endpoint, controlled trial, 2141 incident HD (<12 mo) patients receiving erythropoiesis-stimulating agents (ESAs) were randomly assigned (1:1) to a proactive, high-dose IV iron regimen (iron sucrose 400 mg monthly unless ferritin >700 µg/L and/or TSAT ≥40%) or a reactive, low-dose IV iron regimen (iron sucrose administered if ferritin <200 µg/L or TSAT <20%). The primary outcome was nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, or death, analyzed as time to first event. The hazard ratio (HR) for noninferiority was set at 1.25. Secondary endpoints included all-cause death, infection, and ESA dose.
Results
The median duration of follow-up was 2.1 years (max: 4.4 yr). Patients in the proactive, high-dose IV iron arm received a median (lower quartile [LQ], upper quartile [UQ]) monthly iron dose of 264 (200, 336) mg compared with 145 (100, 190) mg in the reactive, low-dose arm. Median monthly ESA doses were 19.7% lower in the high-dose arm (P<0.001). The incidence of the primary outcome was numerically lower in the high-dose arm than the low-dose arm (30.5% vs 32.7%; adjusted HR [95% CI]: 0.88 [0.76–1.03]; P<0.001 for noninferiority; P=0.11 for superiority). Rates of all-cause death, hospitalization, and infection were similar between the two arms (Table).
Conclusion
Among HD patients, the use of higher doses of IV iron significantly reduced ESA dose requirements without negatively affecting mortality or the incidence of nonfatal CV endpoints.
Selected secondary endpoints
| Outcome | Proactive, High-Dose IV Iron (N=1093) | Reactive, Low-Dose IV Iron (N=1048) | Estimated Treatment Effect | P Value |
| All-cause death | 22.5% | 25.7% | HR (95% CI): 0.84 (0.71–1.00) | 0.054 |
| All-cause hospitalization | 59.6% | 58.8% | HR (95% CI): 1.01 (0.90–1.12) | 0.90 |
| Hospitalization for infection | 29.6% | 29.3% | HR (95% CI): 0.99 (0.85–1.16) | 0.92 |
| All-cause death or myocardial infarction or stroke or hospitalization for heart failure as recurrent events, rate per 100 patient-years | 20.63 | 26.10 | Rate Ratio (95% CI): 0.78 (0.66–0.92) | 0.003 |
Funding
- Government Support - Non-U.S.