Toby Richards1,2,3, Ravishankar Rao Baikady4, Ben Clevenger3,5, Anna Butcher3, Sandy Abeysiri2,3, Marisa Chau2,3, Rebecca Swinson6, Tim Collier6, Matthew Dodd6, Laura Van Dyck6, Iain Macdougall7, Gavin Murphy8, John Browne9, Andrew Bradbury10, Andrew Klein11. 1. Division of Surgery, University of Western Australia, Perth, WA, Australia. 2. Institute of Clinical Trial and Methodology, University College London, London, UK. 3. Division of Surgery, University College London, London, UK. 4. The Royal Marsden NHS Foundation Trust, London, UK. 5. Department of Anaesthesia, Royal National Orthopaedic Hospital, Stanmore, UK. 6. Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK. 7. Department of Renal Medicine, King's College Hospital, London, UK. 8. NIHR Leicester Biomedical Research Centre, Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. 9. School of Public Health, University College Cork, Cork, Ireland. 10. University Department of Vascular Surgery (University of Birmingham), Solihull Hospital, Solihull, UK. 11. Department of Anaesthesia and Intensive Care, Royal Papworth Hospital, Cambridge, UK.
Abstract
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.
RCT Entities:
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.
Authors: Adam K Lewkowitz; Anjlie Gupta; Laura Simon; Bethany A Sabol; Carrie Stoll; Emily Cooke; Roxanne A Rampersad; Methodius G Tuuli Journal: J Perinatol Date: 2019-01-28 Impact factor: 2.521
Authors: Markus M Mueller; Hans Van Remoortel; Patrick Meybohm; Kari Aranko; Cécile Aubron; Reinhard Burger; Jeffrey L Carson; Klaus Cichutek; Emmy De Buck; Dana Devine; Dean Fergusson; Gilles Folléa; Craig French; Kathrine P Frey; Richard Gammon; Jerrold H Levy; Michael F Murphy; Yves Ozier; Katerina Pavenski; Cynthia So-Osman; Pierre Tiberghien; Jimmy Volmink; Jonathan H Waters; Erica M Wood; Erhard Seifried Journal: JAMA Date: 2019-03-12 Impact factor: 56.272
Authors: Johanna W M Aarts; Theodoor E Nieboer; Neil Johnson; Emma Tavender; Ray Garry; Ben Willem J Mol; Kirsten B Kluivers Journal: Cochrane Database Syst Rev Date: 2015-08-12