A multicenter, randomized phase III trial of hetrombopag: a novel thrombopoietin receptor agonist for the treatment of immune thrombocytopenia
Journal of hematology & oncology. 2021;14(1):37
BACKGROUND Hetrombopag, a novel thrombopoietin receptor agonist, has been found in phase I studies to increase platelet counts and reduce bleeding risks in adults with immune thrombocytopenia (ITP). This phase III study aimed to evaluate the efficacy and safety of hetrombopag in ITP patients. METHODS Patients who had not responded to or had relapsed after previous treatment were treated with an initial dosage of once-daily 2.5 or 5 mg hetrombopag (defined as the HETROM-2.5 or HETROM-5 group) or with matching placebo in a randomized, double-blind, 10-week treatment period. Patients who received placebo and completed 10 weeks of treatment switched to receive eltrombopag, and patients treated with hetrombopag in the double-blind period continued hetrombopag during the following open-label 14-week treatment. The primary endpoint was the proportion of responders (defined as those achieving a platelet count of ≥ 50 × 10(9)/L) after 8 weeks of treatment. RESULTS The primary endpoint was achieved by significantly more patients in the HETROM-2.5 (58.9%; odds ratio [OR] 25.97, 95% confidence interval [CI] 9.83-68.63; p < 0.0001) and HETROM-5 (64.3%; OR 32.81, 95% CI 12.39-86.87; p < 0.0001) group than in the Placebo group (5.9%). Hetrombopag was also superior to placebo in achieving a platelet response and in reducing the bleeding risk and use of rescue therapy throughout 8 weeks of treatment. The durable platelet response to hetrombopag was maintained throughout 24 weeks. The most common adverse events were upper respiratory tract infection (42.2%), urinary tract infection (17.1%), immune thrombocytopenic purpura (17.1%) and hematuria (15%) with 24-week hetrombopag treatment. CONCLUSIONS In ITP patients, hetrombopag is efficacious and well tolerated with a manageable safety profile. Trial registration Clinical trials.gov NCT03222843 , registered July 19, 2017, retrospectively registered.
Treatment of Chronic Aplastic Anemia with Chinese Patent Medicine Pai-Neng-Da Capsule () for Replacing Androgen Partially: A Clinical Multi-Center Study
Chinese journal of integrative medicine. 2021
OBJECTIVE To evaluate the efficacy and safety of Pai-Neng-Da Capsule (, panaxadiol saponins component, PNDC) in combination with the cyclosporine and androgen for patients with chronic aplastic anemia (CAA). METHODS A total of 79 CAA patients was randomly divided into 2 groups by a random number table, including PCA group [43 cases, orally PNDC 320 mg/d plus cyclosporine 5 mg/(kg·d) plus andriol 80 mg/d] and CA group [36 cases, orally cyclosporine 5 mg/(kg·d) plus andriol 160 mg/d]. All patients were treated and followed-up for 6 treatment courses over 24 weeks. The complete blood counts, score of Chinese medical (CM) symptoms were assessed and urine routine, electrocardiogram, hepatic and renal function were observed for safety evaluation. Female masculinization rating scale was established according to the actual clinical manifestations to evaluate the accurate degree of masculinization in female CAA patients treated by andriol. RESULTS The effective rates were 88.1% (37/42) in the PCA group and 77.8% (28/36) in the CA group based on the standard for the therapeutic efficacy evaluation of hematopathy. There was no significant difference in the white blood cell (WBC) counts, platelet counts and hemoglobin concentration of peripheral blood between two groups after 6 months treatment. The masculinization score of female patient in the PCA group was significantly lower than the CA group (P<0.05). The mild abdominal distention was observed in 1 cases in the PCA group. In CA group, the abnormalities in the hepatic function developed in 2 cases and the renal disfunction was found in 1 case. CONCLUSION The PNDC possesses certain curative effects in the treatment of CAA without obvious side-effects and can partially replace andriol thereby to reduce the degree of masculinization [Registried at Chinese Clinical Trial Registry (ChicTR1900028153)].
Effect of Two Different Colloid Priming Strategies in Infants Weighing Less Than 5 kg Undergoing On-pump Cardiac Surgeries
Artificial organs. 2019
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.
Balanced crystalloids versus normal saline for fluid resuscitation in critically ill patients: A systematic review and meta-analysis with trial sequential analysis
The American journal of emergency medicine. 2019
INTRODUCTION Fluid resuscitation is a fundamental component of the management of critically ill patients, but whether choice of crystalloid affects patient outcomes remains controversial. Therefore, we performed this meta-analysis to compare the efficacy and safety of balanced crystalloids with normal saline. METHODS We searched the MEDLINE, Cochrane Central and EMBASE up to October 2018 to identify randomized controlled trials (RCTs) that compared balanced crystalloids versus normal saline in critically ill patients. The primary outcome was mortality. The secondary results were the incidence of acute kidney injury (AKI) and risk of receiving renal replacement therapy (RRT). Two authors independently screened articles based on the inclusion and exclusion criteria. The meta-analysis was conducted using Revman 5.3, trial sequential analysis (TSA) 0.9 and STATA 12.0. RESULTS Nine RCTs were identified. The pooled analyses showed that there were no significant differences in mortality (relative risk (RR)=0.93, 95% confidence interval (CI)=0.86, 1.01, P=0.08), incidence of AKI (RR 0.94, 95% CI 0.88, 1.00, P=0.06) or RRT use rate (RR 0.94, 95% CI 0.69, 1.27, P=0.67) between balanced crystalloids and normal saline groups. However, TSA did not provide conclusive evidence. CONCLUSIONS Among critically ill patients receiving crystalloid fluid therapy, use of a balanced crystalloid compared with normal saline did not reduce the mortality, risk of severe AKI or RRT use rate. Further large randomized clinical trials are needed to confirm or refute this finding. TRIAL REGISTRATION A protocol of this meta-analysis has been registered on PROSPERO (registration number: CRD42018094857).
rhTPO combined with chemotherapy and G-CSF for autologous peripheral blood stem cells in patients with refractory/relapsed non-Hodgkin's lymphoma
Cancer management and research. 2019;11:8371-8377
Objective: The mobilization and collection of sufficient autologous peripheral blood stem cells (APBSCs) are important for the fast and sustained reconstruction of hematopoietic function after autologous transplantation. This study aims to evaluate the mobilization effect and safety of thrombopoietin (TPO) combined with chemotherapy + G-CSF for APBSCs in patients with refractory/relapsed non-Hodgkin's lymphoma. Methods: A total of 78 patients were included in the present study. After receiving mobilization chemotherapy, all patients were randomly divided into two groups: TPO group (n=40), patients were given subcutaneous injection of rhTPO + G-CSF, and control group (n=38), patients were given subcutaneous injection of G-CSF. The primary endpoint was the total number of obtained CD34+ cells. The secondary endpoints were the mononuclear cell count, the proportion of target and minimum mobilization, the engraftment time of neutrophils and platelets after APBSCT, the number of platelet and red blood cell infusions, the incidence of infectious fever and fever duration, and TPO-related side effects in patients. Results: TPO participation significantly increased the total CD34+ cell count. A higher proportion of patients in the TPO group achieved the minimum and target CD34+ cells, when compared to the control group. TPO-related adverse events were not observed in either of these groups. In addition, there were no significant differences in engraftment time, the number of platelet and red blood cell transfusions, the incidence of infectious fever, and fever duration between these two groups. Conclusion: TPO combined with chemotherapy + G-CSF can safely and effectively enhance the mobilization effect for APBSCs in patients with refractory/relapsed non-Hodgkin's lymphoma.
Fluid resuscitation in critically ill patients: a systematic review and network meta-analysis
Therapeutics and Clinical Risk Management. 2018;14:1701-1709.
Objective: The aim of this study was to compare the effectiveness of different fluids on critically ill patients who need fluid resuscitation through a systematic review and network meta-analysis (NMA). Data sources: Electronic databases were searched up to March 2018 for randomized controlled trials comparing the effectiveness of different fluids in critically ill patients. The primary outcome was mortality, and the secondary outcomes were the incident of acute kidney injury (AKI) and risk of receiving renal replacement therapy (RRT). A Bayesian NMA was conducted, and the quality of evidence contributing to each network estimate was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group criteria. Results: We deemed 49 trials eligible, including 40,910 participants. The quality of evidence was rated as moderate in most comparisons. There was no significant difference among resuscitation fluids in mortality. NMA at the 9-node level showed the most effective fluid was balanced crystalloid (BC) (80.79%, the ranking of resuscitation fluid based on cumulative probability plots and surface under the cumulative ranking curves [SUCRAs]). NMA at the 10-node level showed that the most effective fluid was Plasma-Lyte (77.52%). Results of sensitivity analyses in mortality did not reveal any significant changes in the findings for primary outcomes. High-molecular-weight hetastarch (H-HES) was associated with an increased incidence of AKI when compared with gelatin (odds ratio [OR], 0.43; 95% credibility interval [CrI], 0.19-0.94), low-molecular-weight hetastarch (L-HES; OR, 0.50; 95% CrI, 0.30-0.87), BC (OR, 0.55; 95% CrI, 0.34-0.88), and normal saline (OR, 0.56; 95% CrI, 0.34-0.93). Meanwhile, H-HES was also associated with an increased risk of receiving RRT when compared with BC (OR, 0.51; 95% CrI, 0.27-0.93) and normal saline (OR, 0.52; 95% CrI, 0.24-0.96). Conclusion: BCs, especially the Plasma-Lyte, are presumably the best choice for most critically ill patients who need fluid resuscitation. Meanwhile, the use of H-HES was associated with an increased incidence of AKI and risk of receiving RRT. Registration: PROSPERO (CRD42017072728).
Optimal sequence of surgical procedures for hemodynamically unstable patients with pelvic fracture: A network meta-analysis
The American Journal of Emergency Medicine. 2018
BACKGROUND The mortality rate of patients with hemodynamic instability due to severe pelvic fracture remains substantial and massive transfusion happens frequently. Angio-embolization, external fixation and preperitoneal pelvic packing of the pelvis are the main managements used to control bleeding in these patients. In this paper, we aimed at characterizing the rationale of these surgical managements, and placed them in optimal management algorithm to compose a new guideline. METHODS We selected controlled trials, assessing safety of management for the intervention of hemorrhagic shock from mortality data, and assessing efficacy from volume of first 24h blood transfusion following hospitalization. Six single and combined managements were extracted as comparison. A pairwise meta-analysis was conducted using a random effect model, and then the analysis was extended to a network meta-analysis. Pooled effect sizes were ranked and demonstrated the probability of being the best treatments for safety and efficacy. RESULTS 13 clinical trials and 24,396 participants were identified for this analysis. The assessment of rank probability indicated that pelvic packing presented the greatest likelihood of improving safety, while external fixation was indicated most efficient among the interventions for controlling hemorrhage. CONCLUSIONS Clinical protocols for guidelines of hemodynamically unstable pelvic fracture patients have been multidirectionally developed. We strongly support the initial application of an external fixator. Provided that patients remain hemodynamically unstable after application of an external fixation, pelvic packing is the next procedure to consider. Angio-embolization is the complementary but not alternative method of choice subsequently.
Clinical study of Shengxuening tablet combined with rHuEPO for the treatment of renal anemia of maintenance hemodialysis patients
Experimental and Therapeutic Medicine. 2016;12((1)):157-160.
The aim of the present study was to investigate the clinical effects of Shengxuening tablet (silkworm excrement) combined with recombinant human erythropoietin (rHuEPO) for the treatment of renal anemia of maintenance hemodialysis (MHD) patients. Seventy-two MHD patients with renal anemia were included in the study and randomly divided into the control (n=34) and observation (n=38) groups. Patients in the control group were treated by hypodermic injection of 100-150 U/(kg.w) rHuEPO and patients in the observation group were treated by rHuEPO + 1.0 g t.i.d. p.o. Shengxuening tablet. The two groups were assisted by conventional treatments including iron, folic acid, vitamin B12 and L-carnitine. After 3 and 6 months, improvement of anemia was compared. After 3 months, the hemoglobin, hematocrit, serum ferritin and transferrin saturation levels of the observation group were significantly higher than those of the control group (p<0.05). In addition, C-reactive protein and superoxide dismutase levels of the observation group were significantly lower than those of the control group (p<0.05). After 6 months, indices of the observation group were ameliorated while the improvement of control group was not obvious, and indices of the observation group were significantly higher than those of the control group (p<0.05). Consumption of rHuEPO in the observation group was significantly less than that of the control group, and the total effective rate was significantly higher than that of the control group (p<0.05). In conclusion, Shengxuening tablet combined with rHuEPO was safe and effective for the treatment of renal anemia of MHD patients.
The effect of tranexamic acid on blood loss in orthognathic surgery: a meta-analysis of randomized controlled trials
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology. 2013;115((5):):595-600.
OBJECTIVE The objective of this article was to evaluate the efficacy of tranexamic acid on blood loss in orthognathic surgery. A meta-analysis was performed. STUDY DESIGN The PubMed and EMBASE electronic databases were searched until June 30, 2012. Eligible studies were restricted to randomized controlled trials (RCTs). RESULTS Four RCTs with 183 patients were included. The results showed that intraoperative blood loss in the tranexamic acid group was statistically reduced (weighted mean difference [WMD] = -93.56, 95% CI = -132.59-54.52, P < .00001). However, the postoperative levels of hemoglobin (Hb) and hematocrit (Hct) have no significant difference compared with placebo groups (WMD = 0.50, 95% CIs = -0.43-1.43, P = .29 and WMD = 0.18, 95% CIs = -1.64-1.99, P = .85, respectively). CONCLUSIONS This meta-analysis confirms that tranexamic acid can effectively reduce intraoperative blood loss in orthognathic surgery, especially by intravenous administration. But, tranexamic acid cannot affect postoperative levels of Hb and Hct. Copyright 2013 Elsevier Inc. All rights reserved.
Tranexamic acid reducing blood transfusion in children undergoing craniosynostosis surgery
Journal of Craniofacial Surgery. 2013;24((1):):299-303.
BACKGROUND Surgical correction of craniosynostosis in children is associated with substantial intraoperative bleeding. Intraoperatively administered tranexamic acid (TXA) can lessen blood loss during orthopedic and cardiovascular surgery, but its efficacy in craniosynostosis surgery is uncertain. Therefore, a meta-analysis performed with published comparative studies was to determine whether TXA could reduce packed red blood cells (or erythrocytes) (PRBCs) transfused and blood loss during pediatric craniosynostosis surgery. METHODS Two PubMed and EMBASE electronic databases were searched until June 2012. Eligible studies were restricted in comparative controlled trials. RESULTS Four studies in 3 articles with 138 patients were included. The results showed that intraoperative administration of TXA can significantly reduce transfusion of PRBCs (weighed mean difference [WMD] = -10.81, 95% confidence interval [CI] = -16.84 to -4.78, P < 0.00001). In the level of blood loss, the meta-analysis on 4 studies showed that the difference was statistically significant (WMD = -20.53, 95% CI = -32.26 to -8.80, P = 0.0006) between the TXA groups and the control groups. However, the subgroup analysis on randomized controlled trials showed that TXA did not significantly reduce blood loss during surgery compared with the placebo group (WMD = -30.79, 95% CIs = -71.72 to 10.14, P = 0.14). CONCLUSIONS Tranexamic acid can significantly reduce the transfusion of PRBCs in children undergoing craniosynostosis surgery. However, there is a controversy on the efficacy of TXA in reducing blood loss. Therefore, new randomized controlled trials to assess the effects of TXA in children with craniosynostosis surgery should be conducted. Journal Article.