1.
Efficacy and safety of CKD-11101 (darbepoetin-alfa proposed biosimilar) compared with NESP in anaemic chronic kidney disease patients not on dialysis
Lee JH, Chung BH, Joo KW, Shin SK, Kim YL, Na KY, Do JY, Park SK, Shin BC, Lee JS, et al
Current medical research and opinion. 2018;:1-17.
Abstract
OBJECTIVE To evaluate the efficacy and safety of CKD-11101 (biosimilar darbepoetin-alfa, Chong Kun Dang Pharm.) compared with NESP(R) in treatment of anaemia in patients with chronic kidney disease not on dialysis. CLINICAL TRIAL REGISTRATION NCT03431623. METHOD In this multicentre, randomized, double-blind study, patients were treated with CKD-11101 and NESP. The efficacy evaluation period (EEP) was 24 weeks, during which patients were treated every 2 weeks. All patients who completed the EEP were treated with CKD-11101 every 2 weeks for the first four weeks and every 4 weeks for the safety evaluation period (SEP), which was from 24 weeks to 52 weeks. The primary efficacy endpoint was the change in mean haemoglobin (Hb) level from baseline to end of EEP and mean dose needed to achieve the target Hb. RESULTS The mean Hb level was increased in both groups during the EEP (both P < 0.001). The difference in mean Hb level change between the two groups was 0.01g/dL (95% CI -0.213, 0.242), indicating that CKD-11101 was equivalent to NESP. The difference in mean administration dose between groups was -1.40mcg (95% CI -6.859, 4.059) included in the equivalent range. The incidence of AEs and ADRs was not different between the two groups, and the frequency of ADRs was favourable in both groups (1.2% in CKD-11101 vs 7.7% in the NESP to CKD-11101 conversion group). CONCLUSION CKD-11101 has an equivalent therapeutic effect as NESP in chronic kidney disease patients with renal anaemia. CKD-11101 can be safely used for long-term treatment and in patients converted from NESP.
2.
Effect of intravenous ferric carboxymaltose on hemoglobin response among patients with acute isovolemic anemia following gastrectomy: the FAIRY randomized clinical trial
Kim YW, Bae JM, Park YK, Yang HK, Yu W, Yook JH, Noh SH, Han M, Ryu KW, Sohn TS, et al
Jama. 2017;317((20)):2097-2104.
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Abstract
Importance: Acute isovolemic anemia occurs when blood loss is replaced with fluid. It is often observed after surgery and negatively influences short-term and long-term outcomes. Objective: To evaluate the efficacy and safety of ferric carboxymaltose to treat acute isovolemic anemia following gastrectomy. Design, Setting, and Participants: The FAIRY trial was a patient-blinded, randomized, phase 3, placebo-controlled, 12-week study conducted between February 4, 2013, and December 15, 2015, in 7 centers across the Republic of Korea. Patients with a serum hemoglobin level of 7 g/dL to less than 10 g/dL at 5 to 7 days following radical gastrectomy were included. Interventions: Patients were randomized to receive a 1-time or 2-time injection of 500 mg or 1000 mg of ferric carboxymaltose according to body weight (ferric carboxymaltose group, 228 patients) or normal saline (placebo group, 226 patients). Main Outcomes and Measures: The primary end point was the number of hemoglobin responders, defined as a hemoglobin increase of 2 g/dL or more from baseline, a hemoglobin level of 11 g/dL or more, or both at week 12. Secondary end points included changes in hemoglobin, ferritin, and transferrin saturation levels over time, percentage of patients requiring alternative anemia management (oral iron, transfusion, or both), and quality of life at weeks 3 and 12. Results: Among 454 patients who were randomized (mean age, 61.1 years; women, 54.8%; mean baseline hemoglobin level, 9.1 g/dL), 96.3% completed the trial. At week 12, the number of hemoglobin responders was significantly greater for ferric carboxymaltose vs placebo (92.2% [200 patients] for the ferric carboxymaltose group vs 54.0% [115 patients] for the placebo group; absolute difference, 38.2% [95% CI, 33.6%-42.8%]; P = .001). Compared with the placebo group, patients in the ferric carboxymaltose group experienced significantly greater improvements in serum ferritin level (week 12: 233.3 ng/mL for the ferric carboxymaltose group vs 53.4 ng/mL for the placebo group; absolute difference, 179.9 ng/mL [95% CI, 150.2-209.5]; P = .001) and transferrin saturation level (week 12: 35.0% for the ferric carboxymaltose group vs 19.3% for the placebo group; absolute difference, 15.7% [95% CI, 13.1%-18.3%]; P = .001); but there were no significant differences in quality of life. Patients in the ferric carboxymaltose group required less alternative anemia management than patients in the placebo group (1.4% for the ferric carboxymaltose group vs 6.9% for the placebo group; absolute difference, 5.5% [95% CI, 3.3%-7.6%]; P = .006). The total rate of adverse events was higher in the ferric carboxymaltose group (15 patients [6.8%], including injection site reactions [5 patients] and urticaria [5 patients]) than the placebo group (1 patient [0.4%]), but no severe adverse events were reported in either group. Conclusion and Relevance: Among adults with isovolemic anemia following radical gastrectomy, the use of ferric carboxymaltose compared with placebo was more likely to result in improved hemoglobin response at 12 weeks. Trial Registration: clinicaltrials.gov Identifier: NCT01725789.
3.
A randomized crossover study of single biweekly administration of epoetin-alpha compared with darbepoetin-alpha in chronic kidney disease patients not receiving dialysis
Na HY, Lee YK, Shin SK, Yang DH, Cheon W, Park JH, Lee JH, Song JO, Jo YI
Kidney Research and Clinical Practice. 2014;33((4)):210-6.
Abstract
BACKGROUND Recent evidence demonstrates that high doses of epoetin-alpha (EPO-alpha) can be administrated at extended intervals, despite its relatively short serum half-life. However, no prospective randomized trials on the effects of extended dosing intervals of EPO-alpha compared with darbepoetin-alpha (DA-alpha) have been performed. This study was designed to investigate whether a single biweekly (Q2W) administration of a high dose of EPO-alpha is as effective as DA-alpha for anemia in chronic kidney disease (CKD) patients not receiving dialysis. METHODS Sixty non-dialysis CKD patients were equally randomized to either Q2W subcutaneous EPO-alpha (10,000 unit) or DA-alpha (50 mug) therapy groups for the first 6 weeks. After a 6-week washout period, the participants of the EPO-alpha and DA-alpha treatment groups switched to the alternate regimen for 6 weeks. The mean hemoglobin (Hb) levels after erythropoiesis stimulating agent (ESA) therapy and percentage change in Hb levels from baseline to the end of the study were analyzed. RESULTS The mean Hb levels of postESA therapy increased significantly compared with those of preESA therapy in both ESA regimens. The percentage increase in Hb levels and erythropoietin resistance index did not show a significant difference between the different ESA regimens. No difference was observed between the regimens regarding mean Hb levels after ESA therapy. Additionally, there were no serious adverse effects leading to withdrawal from treatment. CONCLUSION Biweekly high doses of EPO-alpha therapy may be equally as effective as Q2W DA-alpha therapy in maintaining target Hb levels in non-dialysis CKD patients. IS 2211-9132 IL 2211-9132
4.
Effect of single recombinant human erythropoietin injection on transfusion requirements in preoperatively anemic patients undergoing valvular heart surgery
Yoo YC, Shim JK, Kim JC, Jo YY, Lee JH, Kwak YL
Anesthesiology. 2011;115((5):):929-37.
Abstract
BACKGROUND The authors investigated the effect of a single preoperative bolus of erythropoietin on perioperative transfusion requirement and erythropoiesis in patients with preoperative anemia undergoing valvular heart surgery. METHODS In this prospective, single-site, single-blinded, randomized, and parallel-arm controlled trial, 74 patients with preoperative anemia were randomly allocated to either the erythropoietin or the control group. The erythropoietin group received 500 IU/kg erythropoietin and 200 mg iron sucrose intravenously 1 day before the surgery. The control group received an equivalent volume of normal saline. The primary endpoint was transfusion requirement assessed during the surgery and for 4 days postoperatively. Reticulocyte count and iron profiles were measured serially and compared preoperatively and on postoperative days 1, 2, 4, and 7. RESULTS Transfusion occurred in 32 patients (86%) of the control group versus 22 patients (59%) of the erythropoietin group (P = 0.009). The mean number of units of packed erythrocytes transfused per patient during the surgery and for 4 postoperative days (mean ± SD) was also significantly decreased in the erythropoietin group compared with the control group (3.3 ± 2.2 vs.. 1.0 ± 1.1 units/patient, P = 0.001). The reticulocyte count was significantly greater in the erythropoietin group at postoperative days 4 (P = 0.001) and 7 (P = 0.001). CONCLUSIONS A single intravenous administration of erythropoietin and an iron supplement 1 day before surgery significantly reduced the perioperative transfusion requirement in anemic patients undergoing valvular heart surgery, implicating its potential role as a blood conservation strategy.
5.
Minimal effective dosage of recombinant human erythropoietin in spinal surgery
Lee JH, Lee SH, Oh JH
Clinical Orthopaedics and Related Research. 2003;412:71-6.
Abstract
Preoperative autologous blood donation is one of the most widely used methods of autotransfusion. However securing a predetermined amount of blood (3 units of whole blood) may be difficult in patients with a low preoperative hematocrit. To determine the minimum effective pretreatment dosage of recombinant human erythropoietin required to secure an adequate amount of preoperative blood for autologous transfusion during posterior decompression and instrumentation fusion using the pedicle screw-rod system in the lumbar spine, a prospective randomized clinical trial was done. Forty-five patients who had a preoperative hematocrit less than 40% were selected and were divided blindly into three groups. Fifty units per kilogram of recombinant human erythropoietin seems to be the minimal effective dosage for securing an adequate amount of preoperative autologous blood donation.