Darbepoetin alfa injection versus epoetin alfa injection for treating anemia of Chinese hemodialysis patients with chronic kidney failure: A randomized, open-label, parallel-group, non-inferiority Phase III trail
Chen N, Xing C, Niu J, Liu B, Fu J, Zhao J, Ni Z, Wang M, Liu W, Zhao J, et al
Chronic diseases and translational medicine. 2022;8(1):59-70
BACKGROUND Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0-12.0 g/dL) for the treatment of renal anemia. METHODS Ninety-five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients (n = 95) aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group (n = 56) and a twice or three times per week intravenous epoetin alfa group (n = 39) for 28 weeks, who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease (CKD) and were undergoing hemodialysis or hemofiltration with ESA-naive (erythropoiesis stimulating agent-naive). The primary efficacy profile was the mean Hb level (the non-inferiority margin was -1.0 g/dL, week 21-28); the secondary efficacy profiles were the Hb increase rate (week 0-4), the target Hb achievement cumulative rate and time, the change trends of the Hb levels, and the target Hb maintenance ratio. Adverse events (AEs) were observed and compared, and the efficacy and safety were analyzed between the two treatment groups. Additionally, the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. RESULTS The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (>-1.0 g/dL), and non-inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis. CONCLUSION Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.
Efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection for the treatment of renal anemia in Chinese hemodialysis patients: A randomized, open-label, parallel-group, noninferiority phase III trial
Liu B, Chen N, Zhao J, Yin A, Wu X, Xing C, Jiang G, Fu J, Wang M, Wang R, et al
Chronic diseases and translational medicine. 2022;8(2):134-144
BACKGROUND This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis. METHOD This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. RESULTS Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 > -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis. CONCLUSION The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.
Impact of the Tranexamic Acid on Bleeding Amount of Surgical Patient With Degenerative Spinal Disease: A Randomized Blinded Study
Yan L, Yang H, Jiang H, Yu M, Tan J, Su T, Xu G
Frontiers in surgery. 2021;8:655692
Objective: This study aims to explore the effectiveness and safety of tranexamic acid (TXA) in reducing the bleeding amount of surgical patients with degenerative spinal disease in the perioperative period. Methods: A total of 80 cases of patients, who underwent elective posterior lumbar interbody fusion surgeries under general anesthesia, were enrolled in this study. The age of these patients ranged within 41-69 years old, and the surgical vertebral body segments were ≥2. The ASA classification was Level I or Level II. These patients were divided into two groups using the random number table (n = 40): TXA group and control group (S group). In the TXA group, the skin was incised after the anesthesia induction, and 20 mg/kg of TXA was immediately injected into the vein. The injection continued at a rate of 10 mg·kg(-1)·h(-1) during the surgery, until the surgery was finished. In the S group, IV and pump injection with an equal amount of normal saline (NS) were performed. Then, the RBC, Hb, HCT, AST, ALT, BUN, Cr, PT, TT, APTT, FIB, and D-dimer were measured before the surgery and at 1 day after the surgery, and the SSFQ, intraoperative bleeding amount, homologous transfusion volume, urine volume, infusion quantity, surgical duration, drainage volume at 24 h after the surgery, total bleeding amount and adverse event occurrence at 1 week after the surgery were recorded. Results: The RBC, Hb and HCT at 1 day after the surgery were higher in TXA group than in the S group (average P < 0.05). Intraoperative bleeding, drainage volume at 24 h after surgery, and total blood loss were lower in the TXA group than in the S group (average P < 0.05). The SSFQ score and length of stay were lesser in the TXA group than in the S group (average P < 0.05). The differences in AST, ALT, BUN, Cr, PT, TT, APTT, FIB, and D-dimer at 1 day after the surgery for these two groups of patients had no statistical significance (average P > 0.05). Conclusion: TXA can reduce the bleeding amount of surgical patients with degenerative spinal disease in the perioperative period and decrease the length of stay, but does not increase the occurrence rate of adverse events, thereby promoting postoperative rehabilitation. Clinical Trial Registration: www.chictr.org.cn/index.aspx, identifier: ChiCTR2000033597.
A study of the relationship between dynamic blood rheologic changes and the fluid resuscitation in burn patients Chinese
Xu G, Zhai J, Fang H
Chung-Hua Cheng Hsing Shao Shang Wai Ko Tsa Chih [Chinese Journal of Plastic Surgery & Burns]. 1999;15((4):):294-7.
OBJECTIVE To further study the relationship between hemor rheologic changes and fluid resuscitation in patients with burn and treatment of anemia after burns. METHODS 238 case of burn patients were divided into four groups. In which patients with major burn were allocated to group C and D according to different methods of fluid resuscitation and treatment of anemia. RESULTS Abnormal hemorrheologic parameters could be corrected when transfusion of fresh whole blood and traditional herb medicines were given within 24-48 hours after burn injury. CONCLUSION Dynamic observation of hemorrheologic changes is one of important index in monitoring burn shock and guiding fluid resuscitation. Blood transfusion and traditional medicine can improve abnormal blood rheologic parameters, effectively correct anemia when given early.