Erythropoietin with Iron Supplementation To Prevent Allogeneic Blood Transfusion in Total Hip Joint Arthroplasty

A Randomized, Controlled Trial

5 December 2000 | Volume 133 Issue 11 | Pages 845-854

Background: The optimum regimen of epoetin alfa for prevention of allogeneic blood transfusion is unknown.

Objective: To determine whether a modified regimen of epoetin alfa reduces allogeneic blood transfusion in patients undergoing hip arthroplasty.

Design: Randomized, double-blind, multicenter trial comparing two modified dose regimens of epoetin alfa with placebo.

Setting: 13 teaching hospitals and 4 community hospitals in Canada.

Patients: 201 patients undergoing primary hip arthroplasty who had a hemoglobin concentration of 98 to 137 g/L and did not predonate blood.

Intervention: Patients were assigned in a 3:5:5 ratio to receive four weekly doses of epoetin alfa, 40 000 U (high-dose; n = 44) or 20 000 U (low-dose; n = 79), or placebo (n = 78), starting 4 weeks before surgery. All patients received oral iron supplementation, 450 mg/d, for 42 or more days before surgery.

Measurements: The primary end point was allogeneic transfusion. Secondary end points were thromboembolic events and change in reticulocyte count and hemoglobin concentration.

Results: Both modified epoetin alfa regimens significantly reduced the need for allogeneic transfusion: Five (11.4%) patients in the high-dose group (P = 0.001) and 18 (22.8%) patients in the low-dose group (P = 0.003) had transfusion, compared with 35 (44.9%) patients in the placebo group. The hematologic response was substantial in patients who received epoetin alfa. In the high-dose group, low-dose group, and placebo group, the preoperative increase in reticulocyte count was 58.8, 37.0 and 1.8 x 10⁹ cells/L (P < 0.001), respectively, and the increase in hemoglobin concentration was 19.5, 17.2, and 1.2 g/L (P < 0.001). The incidence of thromboembolic events did not differ among groups.

Conclusions: Both modified epoetin alfa regimens were effective compared with placebo in reducing allogeneic transfusion in patients undergoing hip arthroplasty. Patients who received high-dose epoetin alfa had the lowest transfusion rate.

Author and Article Information

From University of Western Ontario and London Clinical Trials Research Group, London, Ontario; University of Alberta, Edmonton, Alberta; Sir William Osler Health Institute, Hamilton, Ontario; LakeRidge Health Oshawa, Oshawa, Ontario; and Janssen-Ortho Inc., Toronto, Ontario, Canada.

Disclosure: Ms. Wheeler and Dr. Lau are employees of Janssen-Ortho Inc., the manufacturer of epoetin alfa, and own shares in the company. Janssen-Ortho Inc., provided funding for the study.

Acknowledgments: The authors thank the patients who participated in the study and Beverley Jasevicius for assistance in preparing the manuscript.

Grant Support: Sponsored by Janssen-Ortho Inc.

Requests for Single Reprints: Brian G. Feagan, MD, London Clinical Trials Research Group, The John P. Robarts Research Institute, Box 5015, 100 Perth Drive, London, Ontario N6A 5K8, Canada.

Current Author Addresses: Dr. Feagan and Ms. Wong: London Clinical Trials Research Group, The John P. Robarts Research Institute, Box 5015, 100 Perth Drive, London, Ontario N6A 5K8, Canada.

Dr. Kirkley: Fowler Kennedy Sport Medicine Clinic, 1151 Richmond Street, London, Ontario N6A 3K7, Canada.

Dr. Johnston: College Plaza, 506-8215 112 Street NW, Edmonton, Alberta T6G 2C8, Canada.

Dr. Smith: Sir William Osler Health Institute, 105-565 Sanatorium Road, Hamilton, Ontario L9C 7N4, Canada.

Dr. Whitsitt: Oshawa Clinic, 117 King Street East, Oshawa, Ontario L1H 1B9, Canada.

Ms. Wheeler and Dr. Lau: Janssen-Ortho Inc., 19 Green Belt Drive, Toronto, Ontario M3C 1L9, Canada.

Author Contributions: Conception and design: B.G. Feagan, C.J. Wong, A. Kirkley, C.Y. Lau.

Analysis and interpretation of the data: B.G. Feagan, C.J. Wong, C.Y. Lau.

Drafting of the article: B.G. Feagan, C.J. Wong.

Critical revision of the article for important intellectual content: B.G. Feagan, C.J. Wong, C.Y. Lau.

Final approval of the article: B.G. Feagan, C.J. Wong, C.Y. Lau.

Provision of study materials or patients: B.G. Feagan, A. Kirkley, D.W.C. Johnston, F.C. Smith, P. Whitsitt, S.L. Wheeler, C.Y. Lau.

Statistical expertise: C.J. Wong.

Obtaining of funding: B.G. Feagan, S.L. Wheeler, C.Y. Lau.

Administrative, technical, or logistic support: S.L. Wheeler.

Collection and assembly of data: C.J. Wong, S.L. Wheeler.