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1.
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
Abstract
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.
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2.
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
Abstract
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.
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3.
Effects of Tourniquet Application on Faster Recovery after Surgery and Ischemia-Reperfusion Post-Total Knee Arthroplasty, Cementation through Closure versus Full-Course and Nontourniquet Group
Cao Q, Wu Q, Liu Y, He Z, Cong Y, Meng J, Zhao J, Bao N
The journal of knee surgery. 2021
Abstract
Pneumatic tourniquets are used in total knee arthroplasty (TKA) for surgical field visualization and improved cementation; however, their use is controversial. This study aimed to assess the effects of tourniquet application on faster recovery post-TKA. Our hypothesis was that inflammation and limb function would be similar with different tourniquet applications. A prospective randomized double-blinded trial assessed tourniquets effects on postoperative pain, swelling, and early outcome in TKA. In present study, 50 TKAs were enrolled in each group as follows: full course (FC), cementation through closure (CTC), and no tourniquet (NT), CTC as treatment group while FC and NT as control groups. Topical blood samples of 3 mL from the joint cavity and drainage bags were obtained at special time point. At last, all samples such as tumor necrosis factor-a (TNF-a), C-C motif chemokine ligand 2 (CCL2), pentraxin 3 (PTX3), prostaglandin E2 (PGE2), superoxide dismutase 1 (SOD1), and myoglobin (Mb) were detected by ELISA. Active and passive range of motion (ROM) values, pain score by the visual analog scale (VAS), change of thigh circumference were recorded at special time point as well. In topical blood, the change of inflammatory factors, such as TNF-a, PTX3, CCL2, PGE2, SOD1, and Mb, was lower in CTC and NT groups than in FC group (p < 0.01 and 0.05). Although VAS and ROM were comparable preoperatively in three groups (p > 0.05), the perimeter growth rate was lower, pain scores (VAS) were reduced, and ROM values were improved in CTC and NT groups compared with FC group at T4, T5, and T6 postoperatively (p < 0.01 and 0.05). Improved therapeutic outcome was observed in the CTC group, indicating patients should routinely undergo TKA with cementation through closure tourniquet application.
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4.
Hypertension management in elderly with severe intracerebral hemorrhage
Zhao J, Yuan F, Fu F, Liu Y, Xue C, Wang K, Yuan X, Li D, Liu Q, Zhang W, et al
Annals of clinical and translational neurology. 2021;8(10):2059–2069
Abstract
OBJECTIVE To explore the effect of individualized blood pressure (BP)-lowering treatment on the outcomes of elderly patients with severe intracerebral hemorrhage (ICH). METHODS We performed an exploratory analysis of Controlling Hypertension After Severe Cerebrovascular Event (CHASE) trial, which was a multicenter, randomized, controlled clinical trial. Patients with severe ischemic or hemorrhagic stroke (defined as GCS ≤ 12 or NIHSS ≥ 11) were randomized into individualized versus standard BP-lowering treatment in CHASE trial. In this exploratory analysis, patients with severe ICH were included. The primary outcome was the percentage of patients with 90-day functional independence defined as modified Rankin Scale (mRS) ≤2. RESULTS We included 242 patients with severe ICH in the present analysis, consisting of 142 patients aged <65 years and 100 patients aged ≥65 years. There were significant differences between patients aged ≥65 years and <65 years in the proportion of functional independence (47.9% vs. 15.0%, P < 0.001) and good outcome (73.9% vs. 50.0%, P < 0.001) at day 90. In patients aged ≥65 years, the adjusted individualized BP-lowering treatment had an unequivocal effect on the functional independence at day 90 (21.6% vs. 8.2%, odds ratio [OR]: 4.309, 95% confidence interval [CI]: 1.040-17.859, P = 0.044) and improved the neurological deficits at discharge (∆ NIHSS ≥ 4: 64.7% vs. 34.7%, OR: 4.300, 95% CI: 1.599-11.563, P = 0.004). INTERPRETATION Compared with the younger counterparts, the elderly patients (≥65 years) with acute severe ICH might benefit more from individualized BP-lowering treatment.
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Effects of tourniquet application on enhanced recovery after surgery (ERAS) and ischemia-reperfusion post-total knee arthroplasty: Full- versus second half-course application
Cao Q, He Z, Fan Y, Meng J, Yuan T, Zhao J, Bao N
Journal of orthopaedic surgery (Hong Kong). 2020;28(1):2309499019896026
Abstract
PURPOSE Pneumatic tourniquets are used in total knee arthroplasty (TKA) for surgical field visualization and improved cementation; however, their use is controversial. This study aimed to assess the effects of tourniquet application on enhanced recovery post-TKA. METHODS A prospective randomized single-blinded trial assessed tourniquet's effects on postoperative pain, swelling, and early outcome in TKA. One-hundred and two patients with knee osteoarthritis were randomized to full-course (FC) and second half-course (SHC) application (n = 51/group). Tumor necrosis factor-alpha (TNF-alpha), C-C motif chemokine ligand 2(CCL-2), pentraxin-3 (PTX-3), prostaglandin E-2 (PGE-2), superoxide dismutase-1 (SOD-1), and myoglobin (Mb) were assessed by enzyme-linked immunosorbent assay, while the visual analog scale (VAS), range of motion (ROM), and thigh circumference growth rate were recorded. RESULTS Average tourniquet duration significantly differed between the SHC (37.5 +/- 5.1 min) and FC (66.4 +/- 7.2 min) groups (p < 0.01); VAS and thigh circumference growth rate in the SHC group were much lower compared with the FC group, while ROM was higher within 48 h of tourniquet removal (p < 0.01). Blood TNF-alpha, PTX3, CCL2, PGE2, SOD-1, and Mb were lower in the SHC group than the FC group (p < 0.01). Additionally, intraoperative blood loss was significantly elevated in the SHC group than the FC group (p < 0.01), with lower postoperative blood loss in the drain (p = 0.001). Postoperative drainage volume was reduced in the SHC group compared with the FC group (p < 0.01); five and two patients in the FC and SHC groups required blood transfusion, respectively (p = 0.025). Hospital stay tended to be shorter in the SHC group (p = 0.023), and no tourniquet-related complications were recorded. CONCLUSION Improved therapeutic outcome was observed in the SHC group, indicating patients should routinely undergo TKA with SHC tourniquet application.
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6.
Tranexamic Acid for Blood Loss after Transforaminal Posterior Lumbar Interbody Fusion Surgery: A Double-Blind, Placebo-Controlled, Randomized Study
He B, Li Y, Xu S, Ou Y, Zhao J
BioMed research international. 2020;2020:8516504
Abstract
BACKGROUND Transforaminal lumbar interbody fusion (TLIF) may result in significant blood loss and an increase in blood transfusion. Though tranexamic acid (TXA) is widely studied for the hemostasis of arthroplasty, there is little information on the use of TXA for TLIF surgery. METHODS This prospective randomized, double-blind, placebo-controlled trial was conducted to study the influence of TXA (intravenous bolus of 10 mg/kg 15 minutes before skin incision followed by intravenous infusion of 6-8 mg/kg/h up to a total dose of 15 mg/kg during the surgery) on the blood loss and Enhanced Recovery After Surgery (ERAS) after TLIF surgery. 40 patients were randomized into two groups: TXA group (tranexamic acid) and control group (placebo). Baseline characteristics were comparable between the TXA group and the control group before the surgery. Outcomes assessed included blood loss, total postoperative drainage, time for drainage removal, time to ambulation, hospital stay after surgery, postoperative hemoglobin (Hb) one day after surgery, and adverse events. RESULTS Compared to patients in the control group after TLIF surgery, patients in the TXA group have significantly reduced intraoperative hemorrhage and time to ambulation after surgery but show similar hospital stay, postoperative drainage, time for drainage removal, postoperative Hb one day after surgery, and adverse events. CONCLUSIONS TXA shows important ability in controlling blood loss and promoting the ERAS after TLIF surgery.
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7.
Effect of Two Different Colloid Priming Strategies in Infants Weighing Less Than 5 kg Undergoing On-pump Cardiac Surgeries
Zhou C, Tong Y, Feng Z, Cui Y, Zhao M, Hu J, Liu K, Zhao J, Liu J
Artificial organs. 2019
Abstract
OBJECTIVES To explore the effect of two different priming strategies (artificial colloid only vs. artificial colloid combined with human serum albumin) on the prognosis of children weighing less than 5 kg undergoing on-pump congenital heart disease (CHD) surgery. METHODS A total of 65 children weighing less than 5 kg who underwent on-pump CHD surgery in our hospital from September 2016 to December 2017 were enrolled in this study. The children were randomly divided into two groups: artificial colloid priming group (AC group, n=33) and artificial colloid combined albumin priming group (ACA group, n=32). The primary clinical endpoint was the peri-CPB colloid osmotic pressure (COP). Secondary clinical endpoints included perioperative blood product & hemostatic drug consumption, postoperative renal function, coagulation function, postoperative renal function and postoperative recovery parameters. RESULTS COP values were not significant in the priming system as well as peri-CPB time points between the two groups (P>0.05). Platelet consumption in the AC group was significantly lower than that in the ACA group (P<0.05). There were no significant differences in the use of other blood products and hemostatic drugs as well as perioperative coagulation parameters between the two groups (P>0.05). Postoperative length of stay in the AC group was significantly lower than that in the ACA group (P<0.05). There were no significant differences in mortality, postoperative mechanical ventilation time, ICU time and perioperative adverse event (including postoperative AKI) occurrences between the two groups (P>0.05). CONCLUSIONS In the on-pump cardiac surgeries of patients weighting less than 5kg, total colloidal priming would not affect peri-CPB COP values, postoperative coagulation function and blood products consumption. Total artificial colloidal priming strategy is feasible in low-weight patients.
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8.
Role of scalp hypothermia in patients undergoing minimally invasive evacuation of hypertensive cerebral hemorrhage
Zhang Y, Song L, Zhao J
Pakistan journal of medical sciences. 2019;35(5):1451-1455
Abstract
Objective: Hypertensive intracerebral hemorrhage (HICH) is one of the common multiple diseases in neurology. Patients with severe HICH have high risk of disability and poor prognosis. Methods: In order to explore the clinical effect of mild hypothermia combined with micro-traumatic evacuation of cerebral hemorrhage in the treatment of severe HICH, 136 patients with severe HICH were selected and divided into control group and study group using random number table method, 68 each group. The control group was treated with micro-traumatic evacuation of cerebral hemorrhage on the basis of conventional symptomatic treatment, while the study group was treated with mild hypothermia combined with micro-traumatic evacuation of cerebral hemorrhage on the basis of conventional symptomatic treatment. After treatment, the two groups were followed up for eight weeks. Results: The overall effective rate, residual hematoma volume, rebleeding rate, National Institute of Health stroke scale (NIHSS) score, Barthel index score and incidence of adverse reactions after treatment were observed and compared. The overall effective rate of the study group was 89.7%, which was significantly higher than that of the control group (67.6%). The mortality rate of the study group was 3.0%, which was significantly lower than that of the control group (14.7%, P<0.05). The residual hematoma volume and rebleeding rate of the study group were significantly lower than those of the control group (P<0.05). Before treatment, the NIHSS score and Barthel index score of the two groups had no significant differences (P>0.05). After treatment, they were improved, and the improvement of the study group was more significant (P<0.05). The incidence of adverse reactions in the study group was 10.0%, which was significantly lower than that in the control group (36.0%, P<0.05). Conclusion: Mild hypothermia in combination with micro-traumatic evacuation of cerebral hemorrhage has significant clinical effect in the treatment of severe HICH. It can significantly improve neurological function and quality of life, causing few adverse reactions. Its clinical application value is high.
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9.
Evidence-based use of FFP: the influence of a priming strategy without FFP during CPB on postoperative coagulation and recovery in pediatric patients
Miao X, Liu J, Zhao M, Cui Y, Feng Z, Zhao J, Long C, LiS, Yan F, Wang X, et al
Perfusion. 2015;30((2):):140-7.
Abstract
OBJECTIVE Although fresh frozen plasma (FFP) is one of the most commonly used hemostatic agents in clinical specialties today, there is little evidence available supporting its administration. Our present study observed the effects of a priming strategy without FFP during cardiopulmonary bypass (CPB) on postoperative coagulation and clinical recovery in pediatric patients, aiming to supply new evidence for evidence-based use of FFP. METHOD Eighty pediatric patients with congenital heart disease undergoing cardiac surgery with CPB were randomized to receive either 10-20 ml/kg 4% succinylated gelatin (Gelofusine, GEL group, n = 40) or 1-2 units FFP (FFP group, n = 40) in the pump prime. Rapid-thromboelastography (r-TEG) and functional fibrinogen level were measured before skin incision and 15 minutes after heparin reversal. We recorded the volume of chest tube drainage, transfusion requirements and the dosage of pharmacological agents. The ventilation time, ICU length of stay and hospitalization time after surgery were also collected. RESULTS After heparin neutralization, there were significantly elevated levels of fibrinogen in the FFP group, which were manifested by r-TEG parameters MAf and FLEV. No significant differences were observed between the two groups in postoperative bleeding, transfusion requirements and the usage of pharmacological agents. Recovery time was also comparable between the two groups. CONCLUSION In conclusion, prophylactic use of FFP in the priming solution does not provide clinical benefits as presumed. Artificial colloids, such as Gelofusine, can be used safely and effectively as a substitute for FFP in the pump prime. TEG is an effective assessment tool to evaluate postoperative coagulation function in pediatric patients.Copyright © The Author(s) 2014.
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10.
The influence of cardiopulmonary bypass priming without FFP on postoperative coagulation and recovery in pediatric patients with cyanotic congenital heart disease
Miao X, Liu J, Zhao M, Cui Y, Feng Z, Zhao J, Long C, Li S, Yan F, Wang X, et al
European Journal of Pediatrics. 2014;173((11):):1437-43.
Abstract
UNLABELLED Transfusion guidelines have been produced for the evidence-based use of fresh frozen plasma (FFP). However, the inappropriate use of FFP is still a worldwide problem, especially in the prophylactic settings. In the present study, 100 cyanotic pediatric patients (age 6 months to 3 years) undergoing cardiac surgery with cardiopulmonary bypass (CPB) were randomized to receive either 10-20 ml/kg FFP (FFP group, n=50) or 10-20 ml/kg 4 % succinylated gelatin (Gelofusine, GEL group, n=50) in the priming solution. Rapid thromboelastography (r-TEG) was measured before skin incision and 15 min after heparin neutralization. Postoperative renal and hepatic function, mediastinal chest tube drainage, transfusion requirements, and recovery time were observed. The relationships between hematologic and demographic data and postoperative bleeding volume were also analyzed. The results showed that there were significantly elevated levels of fibrinogen (r-TEG parameters: fibrinogen contribution to maximal amplitude (MAf) and fibrinogen level (FLEV)) in the FFP group compared to the GEL group. The postoperative blood loss, total transfusion requirements, and recovery time were not significantly different between the two groups, indicating that there were no obvious clinical benefits of using FFP in the priming. The maximal amplitude (MA) of r-TEG measured after heparin neutralization was correlated with the 6-h postoperative bleeding volume. In addition, preoperative fibrinogen level rather than FFP priming was an independent predictor of postoperative blood loss. CONCLUSION Prophylactic use of FFP in the priming solution does not have obvious clinical benefits in cyanotic congenital heart disease (CCHD) patients. Gelofusine, an artificial colloid, is a safe and effective substitute of FFP in the priming solution. Furthermore, r-TEG can be used as a "real-time" assessment tool to evaluate postoperative bleeding and guide transfusion after cardiac surgery in pediatric patients.