Preoperative intravenous iron for anaemia in elective major open abdominal surgery: the PREVENTT RCT.

BACKGROUND: Anaemia affects 30-50% of patients before they undergo major surgery. Preoperative anaemia is associated with increased need for blood transfusion, postoperative complications and worse patient outcomes after surgery. International guidelines support the use of intravenous iron to correct anaemia in patients before surgery. However, the use of preoperative intravenous iron for patient benefit has not been assessed in the setting of a formal clinical trial. OBJECTIVES: To assess if intravenous iron given to patients with anaemia before major abdominal surgery is beneficial by reducing transfusion rates, postoperative complications, hospital stay and re-admission to hospital, and improving quality of life outcomes. DESIGN: A multicentre, double-blinded, randomised, controlled, Phase III clinical trial, with 1 : 1 randomisation comparing placebo (normal saline) with intravenous iron (intravenous ferric carboxymaltose 1000 mg). Randomisation and treatment allocation were by a secure web-based service. SETTING: The study was conducted across 46 hospitals in England, Scotland and Wales between September 2013 and September 2018. PARTICIPANTS: Patients aged > 18 years, undergoing elective major open abdominal surgery, with anaemia [Hb level of > 90 g/l and < 120 g/l (female patients) and < 130 g/l (male patients)] who could undergo randomisation and treatment 10-42 days before their operation. INTERVENTION: Double-blinded study comparing placebo of normal saline with 1000 mg of ferric carboxymaltose administered 10-42 days prior to surgery. MAIN OUTCOME MEASURES: Co-primary end points were risk of blood transfusion or death at 30 days postoperatively, and rate of blood transfusions at 30 days post operation. RESULTS: A total of 487 patients were randomised (243 given placebo and 244 given intravenous iron), of whom 474 completed the trial and provided data for the analysis of the co-primary end points. The use of intravenous iron increased preoperative Hb levels (mean difference 4.7 g/l, 95% confidence interval 2.7 to 6.8 g/l; p < 0.0001), but had no effect compared with placebo on risk of blood transfusion or death (risk ratio 1.03, 95% confidence interval 0.78 to 1.37; p = 0.84; absolute risk difference +0.8%, 95% confidence interval -7.3% to 9.0%), or rates of blood transfusion (rate ratio 0.98, 95% confidence interval 0.68 to 1.43; p = 0.93; absolute rate difference 0.00, 95% confidence interval -0.14 to 0.15). There was no difference in postoperative complications or hospital stay. The intravenous iron group had higher Hb levels at the 8-week follow-up (difference in mean 10.7 g/l, 95% confidence interval 7.8 to 13.7 g/l; p < 0.0001). There were a total of 71 re-admissions to hospital for postoperative complications in the placebo group, compared with 38 re-admissions in the intravenous iron group (rate ratio 0.54, 95% confidence interval 0.34 to 0.85; p = 0.009). There were no differences between the groups in terms of mortality (two per group at 30 days post operation) or in any of the prespecified safety end points or serious adverse events. CONCLUSIONS: In patients with anaemia prior to elective major abdominal surgery, there was no benefit from giving intravenous iron before the operation. FUTURE WORK: The impact of iron repletion on recovery from postoperative anaemia, and the association with reduced re-admission to hospital for complications, should be investigated. LIMITATIONS: In the preoperative intravenous iron to treat anaemia in major surgery (PREVENTT) trial, all patients included had anaemia and only 20% had their anaemia corrected before surgery. The definition and causality of iron deficiency in this setting is not clear. TRIAL REGISTRATION: Current Controlled Trials ISRCTN67322816 and ClinicalTrials.gov NCT01692418. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25 No. 11. See the NIHR Journals Library website for further project information.

In patients undergoing major surgery, anaemia (low blood count) is a common problem. Anaemia is often a consequence of the disease necessitating surgery and can make people feel tired and unwell. Anaemia increases the need for a blood transfusion at the time of surgery, and patients with anaemia have more complications from surgery, prolonged hospital stay and delayed recovery. Iron deficiency is the most common cause of anaemia. An iron infusion has been shown to be effective to rapidly treat anaemia, but it is not known if this is effective in treating anaemia in the presurgical setting, and whether or not this may benefit patients. The main aim of this study was to assess if intravenous iron can treat anaemia in patients before major surgery and if this will reduce the need for blood transfusion, make patients feel better and, consequently, help them do better during and after surgery. A total of 487 patients with anaemia were recruited from 46 UK hospitals before major abdominal surgery. Patients were randomly allocated to receive an infusion of iron or placebo 10 days to 6 weeks before their surgery. Patients were followed up at 8 weeks and 6 months after their surgery. Intravenous iron increased the blood count in patients before surgery. There was no difference in blood transfusion rates or patient deaths between those who received intravenous iron and those who received placebo. Similarly, there was no difference in the patients' postoperative complications or length of hospital stay. Patients who received iron had a higher blood count at 8 weeks and 6 months post operation and there were fewer re-admissions to hospital for complications. In conclusion, for patients undergoing major surgery, giving intravenous iron to treat anaemia before the operation did not reduce the need for blood transfusion. Further work is needed to evaluate whether or not there is any benefit after discharge from hospital.

Preoperative intravenous iron to treat anaemia before major abdominal surgery (PREVENTT): a randomised, double-blind, controlled trial.

BACKGROUND: Preoperative anaemia affects a high proportion of patients undergoing major elective surgery and is associated with poor outcomes. We aimed to test the hypothesis that intravenous iron given to anaemic patients before major open elective abdominal surgery would correct anaemia, reduce the need for blood transfusions, and improve patient outcomes. METHODS: In a double-blind, parallel-group randomised trial, we recruited adult participants identified with anaemia at preoperative hospital visits before elective major open abdominal surgery at 46 UK tertiary care centres. Anaemia was defined as haemoglobin less than 130 g/L for men and 120 g/L for women. We randomly allocated participants (1:1) via a secure web-based service to receive intravenous iron or placebo 10-42 days before surgery. Intravenous iron was administered as a single 1000 mg dose of ferric carboxymaltose in 100 mL normal saline, and placebo was 100 mL normal saline, both given as an infusion over 15 min. Unblinded study personnel prepared and administered the study drug; participants and other clinical and research staff were blinded to treatment allocation. Coprimary endpoints were risk of the composite outcome of blood transfusion or death, and number of blood transfusions from randomisation to 30 days postoperatively. The primary analysis included all randomly assigned patients with data available for the primary endpoints; safety analysis included all randomly assigned patients according to the treatment received. This study is registered, ISRCTN67322816, and is closed to new participants. FINDINGS: Of 487 participants randomly assigned to placebo (n=243) or intravenous iron (n=244) between Jan 6, 2014, and Sept 28, 2018, complete data for the primary endpoints were available for 474 (97%) individuals. Death or blood transfusion occurred in 67 (28%) of the 237 patients in the placebo group and 69 (29%) of the 237 patients in the intravenous iron group (risk ratio 1·03, 95% CI 0·78-1·37; p=0·84). There were 111 blood transfusions in the placebo group and 105 in the intravenous iron group (rate ratio 0·98, 95% CI 0·68-1·43; p=0·93). There were no significant differences between the two groups for any of the prespecified safety endpoints. INTERPRETATION: Preoperative intravenous iron was not superior to placebo to reduce need for blood transfusion when administered to patients with anaemia 10-42 days before elective major abdominal surgery. FUNDING: UK National Institute of Health Research Health Technology Assessment Program.

Economic evaluation of the NET intervention versus guideline dissemination for management of mild head injury in hospital emergency departments.

BACKGROUND: Evidence-based guidelines for the management of mild traumatic brain injury (mTBI) in the emergency department (ED) are now widely available, and yet, clinical practice remains inconsistent with the guidelines. The Neurotrauma Evidence Translation (NET) intervention was developed to increase the uptake of guideline recommendations and improve the management of minor head injury in Australian emergency departments (EDs). However, the adoption of this type of intervention typically entails an upfront investment that may or may not be fully offset by improvements in clinical practice, health outcomes and/or reductions in health service utilisation. The present study estimates the cost and cost-effectiveness of the NET intervention, as compared to the passive dissemination of the guideline, to evaluate whether any improvements in clinical practice or health outcomes due to the NET intervention can be obtained at an acceptable cost. METHODS AND FINDINGS: Study setting: The NET cluster randomised controlled trial [ACTRN12612001286831]. STUDY SAMPLE: Seventeen EDs were randomised to the control condition and 14 to the intervention. One thousand nine hundred forty-three patients were included in the analysis of clinical practice outcomes (NET sample). A total of 343 patients from 14 control and 10 intervention EDs participated in follow-up interviews and were included in the analysis of patient-reported health outcomes (NET-Plus sample). OUTCOME MEASURES: Appropriate post-traumatic amnesia (PTA) screening in the ED (primary outcome). Secondary clinical practice outcomes: provision of written information on discharge (INFO) and safe discharge (defined as CT scan appropriately provided plus PTA plus INFO). Secondary patient-reported, post-discharge health outcomes: anxiety (Hospital Anxiety and Depression Scale), post-concussive symptoms (Rivermead), and preference-based health-related quality of life (SF6D). METHODS: Trial-based economic evaluations from a health sector perspective, with time horizons set to coincide with the final follow-up for the NET sample (2 months post-intervention) and to 1-month post-discharge for the NET-Plus sample. RESULTS: Intervention and control groups were not significantly different in health service utilisation received in the ED/inpatient ward following the initial mTBI presentation (adjusted mean difference $23.86 per patient; 95%CI - $106, $153; p = 0.719) or over the longer follow-up in the NET-plus sample (adjusted mean difference $341.78 per patient; 95%CI - $58, $742; p = 0.094). Savings from lower health service utilisation are therefore unlikely to offset the significantly higher upfront cost of the intervention (mean difference $138.20 per patient; 95%CI $135, $141; p < 0.000). Estimates of the net effect of the intervention on total cost (intervention cost net of health service utilisation) suggest that the intervention entails significantly higher costs than the control condition (adjusted mean difference $169.89 per patient; 95%CI $43, $297, p = 0.009). This effect is larger in absolute magnitude over the longer follow-up in the NET-plus sample (adjusted mean difference $505.06; 95%CI $96, $915; p = 0.016), mostly due to additional health service utilisation. For the primary outcome, the NET intervention is more costly and more effective than passive dissemination; entailing an additional cost of $1246 per additional patient appropriately screened for PTA ($169.89/0.1363; Fieller's 95%CI $525, $2055). For NET to be considered cost-effective with 95% confidence, decision-makers would need to be willing to trade one quality-adjusted life year (QALY) for 25 additional patients appropriately screened for PTA. While these results reflect our best estimate of cost-effectiveness given the data, it is possible that a NET intervention that has been scaled and streamlined ready for wider roll-out may be more or less cost-effective than the NET intervention as delivered in the trial. CONCLUSIONS: While the NET intervention does improve the management of mTBI in the ED, it also entails a significant increase in cost and-as delivered in the trial-is unlikely to be cost-effective at currently accepted funding thresholds. There may be a scope for a scaled-up and streamlined NET intervention to achieve a better balance between costs and outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612001286831 , date registered 12 December 2012.