Randomised open-label trial comparing intravenous iron and an erythropoiesis-stimulating agent versus oral iron to treat preoperative anaemia in cardiac surgery (INITIATE trial)

British Journal of Anaesthesia

Volumn 128, Issue 5, 2022, Pages 796-805

  Kong, Robert ^a   Hutchinson, Nevil ^a   Hill, Andrew ^a   Ingoldby, Fiona ^b   Skipper, Nicola ^b   Jones, Christopher ^c   Bremner, Stephen ^c   Bruce, Chloe ^c   Wright, Juliet ^d   Lewis, Michael ^a   Newman, Stanton ^e   Chevassut, Timothy ^a   Hildick Smith, David ^a  

^a ROYAL SUSSEX COUNTY HOSPITAL   (United Kingdom)

^b Worthing Hospital   (United Kingdom)

^c UNIVERSITY OF SUSSEX   (United Kingdom)

^d BRIGHTON AND SUSSEX MEDICAL SCHOOL   (United Kingdom)

^e CITY UNIVERSITY   (United Kingdom)

Author keywords

anaemia; cardiac surgery; darbepoetin; intravenous iron; iron deficiency; preoperative; transfusion

Indexed keywords

FERRITIN; FERROUS SULFATE; FRESH FROZEN PLASMA; HEMOGLOBIN; INSULIN; IRON ISOMALTOSE; ORAL ANTIDIABETIC AGENT; RECOMBINANT ERYTHROPOIETIN; TRANEXAMIC ACID; TRANSFERRIN; ANTIANEMIC AGENT; DISACCHARIDE; FERRIC ION; IRON;

AGED; ARTICLE; BLOOD TRANSFUSION; CARDIOPULMONARY BYPASS; CEREBROVASCULAR ACCIDENT; CLINICAL OUTCOME; COMBINATION DRUG THERAPY; COMPARATIVE EFFECTIVENESS; CONTROLLED STUDY; CORONARY ARTERY BYPASS GRAFT; CRYOPRECIPITATE; DIABETES MELLITUS; DRUG DOSE INCREASE; ELECTIVE SURGERY; ERYTHROCYTE TRANSFUSION; FEMALE; FERRITIN BLOOD LEVEL; HEART SURGERY; HEART VALVE SURGERY; HEMOGLOBIN DETERMINATION; HUMAN; IN-HOSPITAL MORTALITY; IRON DEFICIENCY ANEMIA; LENGTH OF STAY; MAJOR CLINICAL STUDY; MALE; MEDIAN STERNOTOMY; MONOTHERAPY; OPEN STUDY; POSTOPERATIVE COMPLICATION; POSTOPERATIVE HEMORRHAGE; PRAGMATIC TRIAL; PREOPERATIVE TREATMENT; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; SUPERIORITY TRIAL; SURGICAL DEBRIDEMENT; THROMBOCYTE TRANSFUSION; TRANSFERRIN SATURATION; ADVERSE EVENT; ANEMIA; ERYTHROPOIESIS; HOSPITAL MORTALITY;

ANEMIA; ANEMIA, IRON-DEFICIENCY; CARDIAC SURGICAL PROCEDURES; DISACCHARIDES; ERYTHROPOIESIS; FERRIC COMPOUNDS; HEMATINICS; HEMOGLOBINS; HOSPITAL MORTALITY; HUMANS; IRON;

EID: 85125735272     PISSN: 00070912     EISSN: 14716771     Source Type: Journal    
DOI: 10.1016/j.bja.2022.01.034     Document Type: Article

References (40)

1. Fowler, A.J., Ahmad, T., Phull, M.K., Allard, S., Gillies, M.A., Pearse, R.M., Meta-analysis of the association between preoperative anaemia and mortality after surgery. Br J Surg 102 (2015), 1314–1324.
2. Lunn, J.N., Elwood, P.C., Anaemia and surgery. Br Med J 3 (1970), 71–73.
3. Kotzé, A., Harris, A., Baker, C., et al. British Committee for Standards in Haematology Guidelines on the identification and management of pre-operative anaemia. Br J Haematol 171 (2015), 322–331.
4. National Institute for Health and Care Excellence. Blood Transfusion (NG24). Available from http://www.nice.org.uk/guidance/ng24, 2015.
5. Tankard, K.A., Park, B., Brovman, E.Y., Bader, A.M., Urman, R.D., The impact of preoperative intravenous iron therapy on perioperative outcomes in cardiac surgery: a systematic review. J Hematol 9 (2020), 97–108.
6. Kulier, A., Levin, J., Moser, R., et al. Impact of preoperative anemia on outcome in patients undergoing coronary artery bypass graft surgery. Circulation 116 (2007), 471–479.
7. Ranucci, M., Di Dedda, U., Castelvecchio, S., et al. Impact of preoperative anemia on outcome in adult cardiac surgery: a propensity-matched analysis. Ann Thorac Surg 94 (2012), 1134–1141.
8. Miceli, A., Romeo, F., Glauber, M., de Siena, P.M., Caputo, M., Angelini, G.D., Preoperative anemia increases mortality and postoperative morbidity after cardiac surgery. J Cardiothorac Surg, 9, 2014, 137.
9. Karkouti, K., Grocott, H.P., Hall, R., et al. Interrelationship of preoperative anemia, intraoperative anemia, and red blood cell transfusion as potentially modifiable risk factors for acute kidney injury in cardiac surgery: a historical multicentre cohort study. Can J Anaesth 62 (2015), 377–384.
10. Horvath, K.A., Acker, M.A., Chang, H., et al. Blood transfusion and infection after cardiac surgery. Ann Thorac Surg 95 (2013), 2194–2201.
11. Ming, Y., Liu, J., Zhang, F., et al. Transfusion of red blood cells, fresh frozen plasma, or platelets is associated with mortality and infection after cardiac surgery in a dose-dependent manner. Anesth Analg 130 (2020), 488–497.
12. Reeves, B.C., Murphy, G.J., Increased mortality, morbidity, and cost associated with red blood cell transfusion after cardiac surgery. Curr Opin Anaesthesiol 21 (2008), 669–673.
13. Wish, J.B., Assessing iron status: beyond serum ferritin and transferrin saturation. Clin J Am Soc Nephrol 1 (2006), S4–S8.
14. Sealed Envelope Ltd, Simple randomisation service. 2012 Available from https://www.sealedenvelope.com/simple-randomiser/v1/. (Accessed 16 November 2012)
15. Zwarenstein, M., Treweek, S., Gagnier, J.J., et al. Improving the reporting of pragmatic trials: an extension of the CONSORT statement. BMJ, 337, 2008, a2390.
16. Zou, G., A Modified Poisson regression approach to prospective studies with binary data. Am J Epidemiol 159 (2004), 702–706.
17. Meier, J., Filipescu, D., Kozek-Langenecker, S., et al. Intraoperative transfusion practices in Europe. Br J Anaesth 116 (2016), 255–261.
18. Munoz, M., Acheson, A.G., Auerbach, M., et al. International consensus statement on the peri-operative management of anaemia and iron deficiency. Anaesthesia 72 (2017), 233–247.
19. Shepshelovich, D., Rozen-Zvi, B., Avni, T., Gafter, U., Gafter-Gvili, A., Intravenous versus oral iron supplementation for the treatment of anemia in CKD: an updated systematic review and meta-analysis. Am J Kidney Dis 68 (2016), 677–690.
20. Sultan, P., Bampoe, S., Shah, R., et al. Oral vs intravenous iron therapy for postpartum anemia: a systematic review and meta-analysis. Am J Obstet Gynecol 221 (2019), 19–29 e3.
21. Bregman, D.B., Morris, D., Koch, T.A., He, A., Goodnough, L.T., Hepcidin levels predict nonresponsiveness to oral iron therapy in patients with iron deficiency anemia. Am J Hematol 88 (2013), 97–101.
22. Ilkovska, B., Kotevska, B., Trifunov, G., Kanazirev, B., Serum hepcidin reference range, gender differences, menopausal dependence and biochemical correlates in healthy subjects. J IMAB 22 (2016), 1127–1131.
23. Wolff, F., De Breucker, S., Pepersack, T., et al. Baseline hepcidin measurement in the differential diagnosis of anaemia for elderly patients and its correlation with the increment of transferrin saturation following an oral iron absorption test. Clin Chem Lab Med 57 (2018), 250–258.
24. Pierelli, L., De Rosa, A., Falco, M., et al. Preoperative sucrosomial iron supplementation increases haemoglobin and reduces transfusion requirements in elective heart surgery patients: a prospective randomized study. Surg Technol Int 39 (2021), 321–328.
25. Koch, T.A., Myers, J., Goodnough, L.T., Intravenous iron therapy in patients with iron deficiency anemia: dosing considerations. Anemia, 2015, 2015, 763576.
26. Padmanabhan, H., Siau, K., Nevill, A.M., et al. Intravenous iron does not effectively correct preoperative anaemia in cardiac surgery: a pilot randomized controlled trial. Interact Cardiovasc Thorac Surg 28 (2019), 447–454.
27. Klein, A.A., Chau, M., Yeates, J.A., et al. Preoperative intravenous iron before cardiac surgery: a prospective multicentre feasibility study. Br J Anaesth 124 (2020), 243–250.
28. Locatelli, F., Aljama, P., Canaud, B., et al. Target haemoglobin to aim for with erythropoiesis-stimulating agents: a position statement by ERBP following publication of the Trial to reduce cardiovascular events with Aranesp therapy (TREAT) study. Nephrol Dial Transplant 25 (2010), 2846–2850.
29. Biboulet, P., Bringuier, S., Smilevitch, P., et al. Preoperative epoetin-alpha with intravenous or oral iron for major orthopedic surgery: a randomized controlled trial. Anesthesiology 129 (2018), 710–720.
30. Spahn, D.R., Schoenrath, F., Spahn, G.H., et al. Effect of ultra-short-term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery: a prospective randomised trial. Lancet 393 (2019), 2201–2212.
31. Keeler, B.D., Simpson, J.A., Ng, O., Padmanabhan, H., Brookes, M.J., Acheson, A.G., Randomized clinical trial of preoperative oral versus intravenous iron in anaemic patients with colorectal cancer. Br J Surg 104 (2017), 214–221.
32. Richards, T., Baikady, R.R., Clevenger, B., et al. Preoperative intravenous iron to treat anaemia before major abdominal surgery (PREVENTT): a randomised, double-blind, controlled trial. Lancet 396 (2020), 1353–1361.
33. De Santo, L., Romano, G., Della Corte, A., et al. Preoperative anemia in patients undergoing coronary artery bypass grafting predicts acute kidney injury. J Thorac Cardiovasc Surg 138 (2009), 965–970.
34. Boening, A., Boedeker, R.-H., Scheibelhut, C., Rietzschel, J., Roth, P., Schonburg, M., Anemia before coronary artery bypass surgery as additional risk factor increases the perioperative risk. Ann Thorac Surg 92 (2011), 805–810.
35. von Heymann, C., Kaufner, L., Sander, M., et al. Does the severity of preoperative anemia or blood transfusion have a stronger impact on long-term survival after cardiac surgery?. J Thorac Cardiovasc Surg 152 (2016), 1412–1420.
36. LaPar, D.J., Hawkins, R.B., McMurry, T.L., et al. Preoperative anemia versus blood transfusion: which is the culprit for worse outcomes in cardiac surgery?. J Thorac Cardiovasc Surg 156 (2018), 66–74 e2.
37. Murphy, G.J., Pike, K., Rogers, C.A., et al. Liberal or restrictive transfusion after cardiac surgery. N Engl J Med 372 (2015), 997–1008.
38. Mazer, C.D., Whitlock, R.P., Shehata, N., Restrictive versus liberal transfusion for cardiac surgery. N Engl J Med 379 (2018), 2576–2577.
39. Tibi, P., McClure, R.S., Huang, J., et al. STS/SCA/AmSECT/SABM update to the clinical practice guidelines on patient blood management. Ann Thorac Surg 112 (2021), 981–1004.
40. Roman, M.A., Abbasciano, R.G., Pathak, S., et al. Patient blood management interventions do not lead to important clinical benefits or cost-effectiveness for major surgery: a network meta-analysis. Br J Anaesth 126 (2021), 149–156.