Supplemental appendix

Additional Investigators

Dr Andy Chapman, Intensivist, Royal Perth Hospital, Wellington Street, Perth, Western Australia, 6000

Elizabeth Jenkinson, Research coordinator, Royal Perth Hospital, Wellington Street, Perth, Western Australia, 6000

Anne Marie Palermo, Research coordinator, Fremantle Hospital, Fremantle, WA, 6005

Brigit Roberts, Research coordinator, Sir Charles Gardner Hospital, Nedlands, Perth, Western Australia, 6009

Trial Eligibility Criteria

Inclusion criteria

  1. Admitted to an ICU for less than 48 hours
  2. Anticipated to require ICU care beyond the next calendar day
  3. Hb less than 100 g/L at any time during the preceding 24 hours
  4. Age 18 years or greater

Exclusion criteria

  1. Suspected or confirmed severe sepsis (two or more Systemic Inflammatory Response Syndrome (SIRS) criteria, suspected or confirmed infection, and one or more organ system failure)
  2. Serum ferritin greater than 1200ng/ml or transferrin saturation greater than 50%
  3. History of haemochromatosis or aceruloplasminaemia
  4. Known prior administration of IV iron in the preceding 3 months
  5. Jehovah’s Witness or other documented exclusion to receiving blood products
  6. Receiving ESA (e.g. epoetin or darbepoeitin) in the 3 months prior to ICU admission
  7. Known hypersensitivity to intravenous iron
  8. Pregnancy
  9. Treatment intent is palliative
  10. Death is deemed imminent and inevitable
  11. Weight less than 40kg
  12. Participating in competing study

Minor and Major Bleeding Definitions

Minor bleeding = overt or suspected bleeding or bleeding apparent on imaging studies without haemodynamic compromise (SBP<90mmHg) and not requiring transfusion or fluid resuscitation, specific diagnostic tests or interventions or initiation or escalation in vasopressor requirement

Major bleeding = overt or suspected bleeding or bleeding apparent on imaging studies with haemodynamic compromise (SBP<90mmhg) or requiring transfusion or fluid resuscitation, specific diagnostic tests or interventions or initiation or escalation in vasopressor requirement

Power calculation for a future trial of IV iron

On the basis of the results of this study (baseline mean RBC transfusion of 1.9 units, standard deviation 3, mean difference 0.5 RBC units), a future trial of 567 participants per group would have 80% power to detect a change in RBC units transfused of 0.5 (alpha=0.05). The sample size calculation would then have to be inflated to account for non-normal distribution (20%), potential decrease in baseline RBC use over time (5%) and loss to follow up (10%). This would give a final trial sample size of approximately 1572 participants.

Figure 2 Histogram of Hb at hospital discharge for IV iron and Placebo Groups

Figure 3. Total RBC units by study day for patients remaining in ICU

Figure 4. Median Hb by study day for patients remaining in ICU