TY - JOUR
T1 - Preoperative intravenous iron for anaemia in elective major open abdominal surgery
T2 - The PREVENTT RCT
AU - Richards, Toby
AU - Baikady, Ravishankar Rao
AU - Clevenger, Ben
AU - Butcher, Anna
AU - Abeysiri, Sandy
AU - Chau, Marisa
AU - Swinson, Rebecca
AU - Collier, Tim
AU - Dodd, Matthew
AU - Van Dyck, Laura
AU - Macdougall, Iain
AU - Murphy, Gavin
AU - Browne, John
AU - Bradbury, Andrew
AU - Klein, Andrew
N1 - Funding Information:
Declared competing interests of authors: Andrew Klein reports grants and personal fees from Pharmacosmos A/S (Holbaek, Denmark) and Fisher and Paykel (Auckland, New Zealand), personal fees from Vifor Pharma (Glattbrugg, Switzerland) and Masimo (Irvine, CA, USA), and grants from Haemonetics® (Braintree, MA, USA) and HemoSonics (Charlottesville, VA, USA) outside the submitted work. Iain Macdougall reports grants and personal fees from Vifor Pharma outside the submitted work. Ravishankar Rao Baikady reports grants and other support from Pharmacosmos UK (Reading, UK), Vifor Pharma, Novo Nordisk A/S (Bagsværd, Denmark) and Fresenius Kabi (Bad Homburg, Germany) outside the submitted work. Gavin Murphy reports grants from Zimmer Biomet (Warsaw, IN, USA) and other from Terumo Corporation (Tokyo, Japan) outside the submitted work, and is part of Clinical Trials Units (CTUs) funded by the National Institute for Health Research (NIHR) CTU Standing Advisory Committee. Toby Richards reports grants from NIHR Health Technology Assessment (HTA) during the conduct of the study, grants, personal fees and non-financial support from Pharmocosmos and Vifor Pharma, and personal fees from Tiash Ltd (Republic of Singapore) outside the submitted work. Sandy Abeysiri reports grants from NIHR HTA during the conduct of the study and has been working on PREVENTT as part of her PhD at University College London. She has also worked at The Iron Clinic (London, UK), which provides intravenous iron therapy. Andrew Bradbury reports membership of the NIHR HTA Interventional Procedures Panel, NIHR HTA Prioritisation Group, NIHR HTA Remit and Competitiveness Committee and NIHR HTA Hospital Based Care Methods Group (2014–2020).
Funding Information:
The research reported in this issue of the journal was funded by the HTA programme as project number 10/104/06. The contractual start date was in September 2012. The draft report began editorial review in November 2019 and was accepted for publication in July 2020. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.
Funding Information:
This report presents independent research funded by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, NETSCC, the HTA programme or the Department of Health and Social Care. If there are verbatim quotations included in this publication the views and opinions expressed by the interviewees are those of the interviewees and do not necessarily reflect those of the authors, those of the NHS, the NIHR, NETSCC, the HTA programme or the Department of Health and Social Care.
Funding Information:
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.
Funding Information:
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.
Publisher Copyright:
© 2021 Richards et al.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85102097922&partnerID=8YFLogxK
U2 - 10.3310/HTA25110
DO - 10.3310/HTA25110
M3 - Article
C2 - 33632377
AN - SCOPUS:85102097922
SN - 1366-5278
VL - 25
JO - Health Technology Assessment
JF - Health Technology Assessment
IS - 11
ER -