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.

The impact of maintaining serum potassium ≥3.6 mEq/L vs ≥4.5 mEq/L on the incidence of new-onset atrial fibrillation in the first 120 hours after isolated elective coronary artery bypass grafting - study protocol for a randomised feasibility trial for the proposed Tight K randomized non-inferiority trial.

BACKGROUND: Atrial fibrillation (AF) occurs in approximately one in three patients after cardiac surgery, and is associated with increased short-term and long-term mortality, intensive care unit (ICU) and hospital stay, and increased cost of care. In an attempt to reduce AF incidence in these patients, serum potassium (K+) levels are commonly maintained at the high end of normal (4.5-5.5 mEq/L). However, such potassium supplementation is without proven benefit, and is not without negative consequences. It carries clinical risk, negatively impacts patient experience and is both time-consuming and costly. This protocol describes a randomised controlled pilot trial to assess the feasibility of a proposed randomised non-inferiority trial to investigate the impact of maintaining serum potassium ≥ 3.6 mEq/L vs ≥ 4.5 mEq/L on the incidence of new-onset atrial fibrillation in the first 120 hours after isolated elective coronary artery bypass grafting. METHODS: Design: this is a randomized feasibility trial as a pilot for a randomized non-inferiority trial. PARTICIPANTS: are 160 patients undergoing isolated coronary artery bypass grafting at two centres. Allocation: patients will be randomized (1:1) to protocols aiming to maintain serum potassium at either ≥ 3.6 mEq/L ("relaxed control") or ≥ 4.5 mEq/L ("tight control"). Primary analytic aim: was to assess the feasibility and acceptability of planning and delivering the intervention and trial methods to inform a full-scale non-inferiority trial. OUTCOME: the primary indicative efficacy outcome measures being field-tested are feasibility of participant recruitment and randomization, maintaining a protocol violation rate < 10%, and retaining 90% patient follow up 28 days after surgery. The primary clinical outcome measure of the future full "Tight K Study" will be incidence of AF after cardiac surgery. DISCUSSION: The Tight K Pilot will assess the feasibility of conducting the full trial, which is intended to confirm or refute the efficacy of current potassium management in preventing AF after cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03195647 . Registered on 23 May 2017. Last updated 19June 2017.