SUBCUTANEOUS ADMINISTRATION OF RECOMBINANT-HUMAN-ERYTHROPOIETIN BEFORE CARDIAC-SURGERY - A DOUBLE-BLIND, MULTICENTER TRIAL IN JAPAN

Background: Dose and injection times have not previously been determined for subcutaneously administered recombinant human erythropoietin that would allow sufficient deposition of blood for autologous use in cardiac surgery. Study Design and Methods: A double-blind, multicenter trial of placebo (Group 1) and recombinant human erythropoietin at 12,000 IU (Group 2) and at 24,000 IU (Group 3) was performed on 114 patients at 26 institutions to determine the dosage that would permit an 800-g preoperative deposit of blood for autologous use. The test drug was administered subcutaneously on Days 21, 14, and 7 prior to operation, and oral iron preparations at 200 mg per day were given for 21 days. There were 28 patients in Group 1, 28 in Group 2, and 30 in Group 3, with 28 excluded for a violation of the protocol. Results: Blood was safely drawn 14 and 7 days before operation from 22 patients in Group 1 (78.6%), from 26 in Group 2 (92.9%), and from all patients in Group 3 (p = 0.018). The hemoglobin level on the day before operation decreased by 1.1 +/- 1.1 g per dL (11 +/- 11 g/L) in Group 1 and by 0.9 +/- 0.9 g per dL (9 +/- 9 g/L) in Group 2 and rose by 0.1 +/- 0.8 g per dL (1 +/- 8 g/L) in Group 3, compared to Initial levels. Allogeneic blood transfusion could be avoided in 62, 89, and 90 percent of Group 1, 2, and 3 patients, respectively (p = 0.013). Conclusion: The present study shows that subcutaneously administered recombinant human erythropoietin at a dose of 24,000 IU per week for 3 weeks is effective and sufficient to allow the safe deposition of 800 g of blood for autologous use in cardiac surgery.