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 determin ed for subcutaneously administered recombinant human erythropoietin th at would allow sufficient deposition of blood for autologous use in ca rdiac surgery. Study Design and Methods: A double-blind, multicenter t rial of placebo (Group 1) and recombinant human erythropoietin at 12,0 00 IU (Group 2) and at 24,000 IU (Group 3) was performed on 114 patien ts 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, w ith 28 excluded for a violation of the protocol. Results: Blood was sa fely 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 decrease d 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 stud y shows that subcutaneously administered recombinant human erythropoie tin at a dose of 24,000 IU per week for 3 weeks is effective and suffi cient to allow the safe deposition of 800 g of blood for autologous us e in cardiac surgery.