Randomized and dose-escalation trials of recombinant human serum albumin /granulocyte colony-stimulating factor in patients with breast cancer receiving anthracycline-containing chemotherapy
BMC cancer. 2021;21(1):341
BACKGROUND To evaluate the efficacy and safety of recombinant human serum albumin /granulocyte colony-stimulating factor (rHSA/G-CSF) in breast cancer following receipt of cytotoxic agents. METHODS The phase 1b trial assessed the pharmacokinetics, pharmacodynamics, and safety of dose-escalation, ranging from rHSA/G-CSF 1800 μg, 2100 μg, and 2400 μg. Randomized controlled phase 2b trial was further conducted to ensure the comparative efficacy and safety of rHSA/G-CSF 2400 μg and rhG-CSF 5 μg/kg. In multicenter, randomized, open-label, parallel, phase 2 study, participants treated with anthracycline-containing chemotherapy were assigned in a ratio 1:1:1 to receive double delivery of rHSA/G-CSF 1200 μg, 1500 μg, and continuous rhG-CSF 5 μg/kg. RESULTS Between December 16, 2014, to July 23, 2018, a total of 320 patients were enrolled, including 25 individuals in phase 1b trial, 80 patients in phase 2b trial, and 215 participants in phase 2 study. The mean duration of agranulocytosis during the first chemotherapeutic intermission was observed as 1.14 ± 1.35 days in rHSA/G-CSF 1500 μg, which was comparable with that of 1.07 ± 0.97 days obtained in rhG-CSF control (P = 0.71). Safety profiles were assessed to be acceptable ranging from rHSA/G-CSF 1800 μg to 2400 μg, while the double delivery of HSA/G-CSF 2400 μg failed to meet the noninferiority in comparison with rhG-CSF. CONCLUSION The prospective randomized controlled trials demonstrated that rHSA/G-CSF was efficacious and well-tolerated with an approachable frequency and expense of application for prophylactic management of agranulocytosis. The double delivery of rHSA/G-CSF 1500 μg in comparisons with paralleling G-CSF preparations is warranted in the phase 3 trial. TRIAL REGISTRATION ClinicalTrials.gov identifiers: NCT02465801 (11/17/2014), NCT03246009 (08/08/2017), NCT03251768 (08/07/2017).
Comparative efficacy and safety of topical hemostatic agents in primary total knee arthroplasty: A network meta-analysis of randomized controlled trials
BACKGROUND Topical hemostatic agents are commonly used for reducing perioperative blood loss and transfusion requirement in primary total knee arthroplasty (TKA), although the optimal option has yet to be defined. This study aimed to evaluate the efficacy and safety of topical hemostatic agents and rank the best intervention using the network meta-analysis (NMA) method. METHODS We searched Web of science, PubMed, and Cochrane Library database up to April 2020, for randomized controlled trials (RCTs) on topical hemostatic agents in primary TKA. The quality of included studies was assessed using the Cochrane "risk of bias" tool. Direct and indirect comparisons were performed for the result of network meta-analysis followed by consistency test. RESULTS Thirty seven RCTs with 3792 patients were included in this NMA and the pooled results indicated that tranexamic acid plus diluted epinephrine (TXA+DEP) displayed the highest efficacy in reducing total blood loss, hemoglobin drop and transfusion requirement. None of the included treatments was found to increase risk of thromboembolic events compared to placebo. According to the results of ranking probabilities, TXA+DEP had the highest possibility to be the best topical hemostatic agent with regard to the greatest comparative efficacy and a relatively high safety level. CONCLUSION Current evidence supports that administration of TXA+DEP may be the optimal topical hemostatic agent to decrease blood loss and transfusion requirement in primary TKA. More direct studies that focused on the topical application of TXA+DEP versus other treatments are needed in the future.
The efficacy and safety of topical tranexamic acid for spinal surgery: a meta-analysis
Current pharmaceutical design. 2021
BACKGROUND Spinal surgeries are often accompanied by significant blood loss both intraoperatively and postoperatively. Excessive blood loss caused by surgery may lead to several harmful medical consequences. Tranexamic acid (TXA) is a kind of antifibrinolytic agent that has been widely used in spinal surgery. Currently, it is commonly accepted that intravenous TXA (ivTXA) can reduce blood loss in spinal fusion surgeries. Compared with ivTXA, topical TXA (tTXA) seems to be much easier to administer. This advantage provides a maximum concentration of TXA at the hemorrhagic site with little to no TXA entering the circulation. OBJECTIVE To evaluate the effect of tTXA on blood loss during and after spinal surgery via a comprehensive meta-analysis of the published data in randomized controlled trials (RCTs) and other comparative cohort studies. METHODS A comprehensive search of PubMed, EMBASE, the Web of Science, and the Cochrane Central Register of Controlled Trials were performed for RCTs and other comparative cohort studies on the effect of tTXA on blood loss during and after spinal surgery. The outcomes were total blood loss, hidden blood loss, intraoperative blood loss, total postoperative drainage volume, drainage tube duration postoperatively, drainage volume and drainage of blood content at postoperative day (POD) 1 and POD2, length of hospital stay, number of patients who received a blood transfusion, serum HB level at POD1, operative timespan, side effects, and complications. The final search was performed in October 2020. We followed the PRISMA guideline, and the registration number is INPLASY202160028. RESULTS In total, six studies with 481 patients were included. tTXA treatment, compared with the control conditions, can significantly reduce the total blood loss, hidden blood loss, total postoperative drainage volume, and several patients receiving blood transfusions; reduce the drainage volume and drainage of blood content at POD1; shorten the drainage tube duration postoperatively and length of hospital stay, and enhance the serum HB level at POD1 for spinal surgery. tTXA treatment did not significantly influence the intraoperative blood loss, drainage volume, or drainage of blood content at POD2 or the operative duration. CONCLUSION Compared with control conditions, tTXA has high efficacy in reducing blood loss, and drainage volume enable quick rehabilitation and has a relatively high level of safety in spinal surgery.
The comparative efficacies of intravenous administration and intra-articular injection of tranexamic acid during anterior cruciate ligament reconstruction for reducing postoperative hemarthrosis: a prospective randomized study
BMC musculoskeletal disorders. 2021;22(1):114
BACKGROUND Hemarthrosis after anterior cruciate ligament (ACL) reconstruction can create many adverse joint effects. Tranexamic acid (TXA) can be used to minimize hemarthrosis and associated pain after ACL reconstruction. We aimed to compare the efficacies of intravenous (IV) administration and intra-articular (IA) injection of TXA during ACL reconstruction for reducing postoperative hemarthrosis. METHODS A total of 120 patients who underwent arthroscopic ACL reconstruction were included in this prospective and randomized study. All patients were randomized into three groups: IV group, IA group and placebo group. Patients in the IV group received intravenously administered TXA (15 mg/kg in 100 mL of saline solution) 10 min before tourniquet release; patients in the IA group received intra-articular TXA (15 mg/kg in 100 mL of saline solution) injected via the drainage tube; and patients in the placebo group received an equivalent volume of normal saline administered into the knee joint cavity and intravenously. Drainage tubes were removed 24 h after surgery, and all enrolled patients experienced a 4-week follow-up period. The drain output volume, visual analogue scale (VAS) score, patellar circumference, hemarthrosis grade and Lysholm score of all patients were recorded. RESULTS Both the IV group and the IA group had significantly lower drain output volumes at day 1, lower VAS scores at weeks 1 and 2, smaller patellar circumferences at weeks 1 and 2, and lower hemarthrosis grades at weeks 1 and 2 than the placebo group (p < 0.05). There were no significant differences in drain output volume, VAS score, patellar circumference or hemarthrosis grade between the IV group and the IA group at any time point (p > 0.05). No obvious differences in Lysholm score were observed between any pair of groups at week 4 (p > 0.05)). Neither infection nor deep vein thrombosis occurred in any group. CONCLUSIONS Both intravenous administration and intra-articular injection can reduce intra-articular hemarthrosis, joint pain and swelling during ACL reconstruction. No significant difference in the efficacies of reducing hemarthrosis, joint pain and swelling was found between intravenous administration and intra-articular injection. TRIAL REGISTRATION The study was registered by the Chinese Clinical Trial Registry (The comparative efficacies of intravenous administration and intra-articular injection of tranexamic acid during anterior cruciate ligament reconstruction; ChiCTR-INR-17012217 ; August 1, 2017).
Efficacy of Platelet-Rich Plasma Versus Placebo in the Treatment of Tendinopathy: A Meta-analysis of Randomized Controlled Trials
Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine. 2021
OBJECTIVE To evaluate the efficacy of platelet-rich plasma (PRP) injections versus placebo in the treatment of tendinopathy. DATA SOURCES We performed a systematic literature search in MEDLINE, Embase, Scopus, CINAHL, Cochrane Library, and ClinicalTrials.gov through November 2020 to identify randomized controlled trials (RCTs) that evaluated the clinical efficacy of PRP versus placebo for the treatment of tendinopathy. Outcomes were analyzed on an intention-to-treat basis with random-effects models. MAIN RESULTS A total of 13 RCTs were included in this meta-analysis. The pooled analysis showed no significant difference in pain relief at 4 to 6 weeks (standard mean difference [SMD]: -0.18, 95% confidence intervals [CI]: -0.62 to 0.26), 12 weeks (SMD: -0.14, 95% CI: -0.55 to 0.26), and ≥24 weeks (SMD: -0.56, 95% CI: -1.16 to 0.05) or function improvement at 4 to 6 weeks (SMD: 0.11, 95% CI: -0.13 to 0.35), 12 weeks (SMD: 0.18, 95% CI: -0.13 to 0.49), and ≥24 weeks (SMD: 0.26, 95% CI: -0.14 to 0.66) for PRP compared with placebo in the treatment of tendinopathy. The sensitivity analysis indicated no significant difference in pain relief or function improvement at 12 weeks between PRP and placebo for different types of tendinopathies, treatment regimens, leukocyte concentrations, or cointerventions. CONCLUSIONS Platelet-rich plasma injection was not found to be superior to placebo in the treatment of tendinopathy, as measured by pain relief and functional improvement at 4 to 6, 12, and ≥24 weeks.
Efficacy and Safety of Therapeutic-Dose Heparin vs Standard Prophylactic or Intermediate-Dose Heparins for Thromboprophylaxis in High-risk Hospitalized Patients With COVID-19: The HEP-COVID Randomized Clinical Trial
JAMA internal medicine. 2021
IMPORTANCE Hospitalized patients with COVID-19 are at risk for venous and arterial thromboembolism and death. Optimal thromboprophylaxis dosing in high-risk patients is unknown. OBJECTIVE To evaluate the effects of therapeutic-dose low-molecular-weight heparin (LMWH) vs institutional standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS The HEP-COVID multicenter randomized clinical trial recruited hospitalized adult patients with COVID-19 with D-dimer levels more than 4 times the upper limit of normal or sepsis-induced coagulopathy score of 4 or greater from May 8, 2020, through May 14, 2021, at 12 academic centers in the US. INTERVENTIONS Patients were randomized to institutional standard prophylactic or intermediate-dose LMWH or unfractionated heparin vs therapeutic-dose enoxaparin, 1 mg/kg subcutaneous, twice daily if creatinine clearance was 30 mL/min/1.73 m2 or greater (0.5 mg/kg twice daily if creatinine clearance was 15-29 mL/min/1.73 m2) throughout hospitalization. Patients were stratified at the time of randomization based on intensive care unit (ICU) or non-ICU status. MAIN OUTCOMES AND MEASURES The primary efficacy outcome was venous thromboembolism (VTE), arterial thromboembolism (ATE), or death from any cause, and the principal safety outcome was major bleeding at 30 ± 2 days. Data were collected and adjudicated locally by blinded investigators via imaging, laboratory, and health record data. RESULTS Of 257 patients randomized, 253 were included in the analysis (mean [SD] age, 66.7 [14.0] years; men, 136 [53.8%]; women, 117 [46.2%]); 249 patients (98.4%) met inclusion criteria based on D-dimer elevation and 83 patients (32.8%) were stratified as ICU-level care. There were 124 patients (49%) in the standard-dose vs 129 patients (51%) in the therapeutic-dose group. The primary efficacy outcome was met in 52 of 124 patients (41.9%) (28.2% VTE, 3.2% ATE, 25.0% death) with standard-dose heparins vs 37 of 129 patients (28.7%) (11.7% VTE, 3.2% ATE, 19.4% death) with therapeutic-dose LMWH (relative risk [RR], 0.68; 95% CI, 0.49-0.96; P = .03), including a reduction in thromboembolism (29.0% vs 10.9%; RR, 0.37; 95% CI, 0.21-0.66; P < .001). The incidence of major bleeding was 1.6% with standard-dose vs 4.7% with therapeutic-dose heparins (RR, 2.88; 95% CI, 0.59-14.02; P = .17). The primary efficacy outcome was reduced in non-ICU patients (36.1% vs 16.7%; RR, 0.46; 95% CI, 0.27-0.81; P = .004) but not ICU patients (55.3% vs 51.1%; RR, 0.92; 95% CI, 0.62-1.39; P = .71). CONCLUSIONS AND RELEVANCE In this randomized clinical trial, therapeutic-dose LMWH reduced major thromboembolism and death compared with institutional standard heparin thromboprophylaxis among inpatients with COVID-19 with very elevated D-dimer levels. The treatment effect was not seen in ICU patients. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04401293.
Effect of platelet-rich fibrin on the control of alveolar osteitis, pain, trismus, soft tissue healing, and swelling following mandibular third molar surgery: an updated systematic review and meta-analysis
International journal of oral and maxillofacial surgery. 2020
The purpose of this study was to estimate the effect of platelet-rich fibrin (PRF) on the control of alveolar osteitis (AO), pain, trismus, soft tissue healing, and swelling following mandibular third molar surgery. A comprehensive search of the literature was conducted through PubMed, Embase, Web of Science, and Cochrane Library up to May 2019. Randomized controlled studies conforming to the inclusion criteria were included. The record screening and data extraction were conducted by two authors independently. The risk of bias assessment was performed according to the guidelines recommended by the Cochrane Collaboration. The quantitative analysis was performed using RevMan version 5.3. Nineteen studies were included in the systematic review and 17 studies were eligible for the meta-analysis. The use of PRF significantly reduced the incidence of AO and postoperative pain when compared to the controls (AO: relative risk 0.43, 95% confidence interval (CI) 0.28 to 0.65, Z=3.90, P<0.0001 (I(2)=0%); pain: day 1, standardized mean difference (SMD) -1.12, 95% CI -1.87 to -0.37, Z=2.93, P=0.003 (I(2)=95%); day 3, SMD -0.93, 95% CI -1.48 to -0.38, Z=3.30, P=0.001 (I(2)=92%); day 7, SMD -1.84, 95% CI -2.98 to -0.71, Z=3.19, P=0.001 (I(2)=97%)). Additionally, the result showed a better soft tissue healing when PRF was used (mean difference -0.63, 95% CI -1.08 to -0.18, Z=2.76, P=0.006 (I(2)=90%)). The use of PRF reduced the incidence of AO and postoperative pain following third molar surgery. Furthermore, PRF may also improve the postoperative soft tissue healing.
Sedated second-look endoscopy-guided therapy prevents early rebleeding after variceal ligation for acute variceal bleeding
Journal of digestive diseases. 2020
OBJECTIVE The efficacy and safety of second-look endoscopy (SLE)-guided therapy to prevent early post-endoscopic variceal ligation (EVL) bleeding have not been validated. The objective of the study was to determine whether SLE-guided therapy after EVL influences outcomes. METHODS Consecutive cirrhotic patients with large oesophageal varices (EVs) receiving successful EVL for acute variceal bleeding (AVB) or secondary prophylaxis were enrolled. The patients were randomized into the SLE group or non-SLE group (NSLE) 10 days after EVL. Additional endoscopic interventions and proton pump inhibitor and octreotide administration were used based on the SLE findings. The early post-EVL rebleeding and mortality rates were compared. RESULTS A total of 252 out of 438 patients were included. Early post-EVL rebleeding (13.5% vs. 4.8%, P = 0.016) and bleeding-caused mortality (4.8% vs. 0, P = 0.013) were more frequently observed in the NSLE group than in the SLE group. However, SLE could reduce early rebleeding and mortality rates in patients receiving EVL for AVB only but not in those receiving secondary prophylaxis. Patients with Child-Pugh class B/C (HR: 8.77, P = 0.034), AVB at index EVL (HR: 3.62, P = 0.003), non-selective beta-blocker (NSBB) discontinuation after randomization (HR: 4.68, P = 0.001) and non-SLE (HR: 2.63, P = 0.046) were more likely to have early post-EVL rebleeding. There were no serious adverse events during SLE. CONCLUSION SLE-guided therapy reduces early post-EVL rebleeding and mortality rates in patients with cirrhosis and large EVs receiving EVL for AVB. This article is protected by copyright. All rights reserved.
Role of Xingnaojing Injection in treating acute cerebral hemorrhage: A systematic review and meta-analysis
Medicine (Baltimore). 2020;99(15):e19648
BACKGROUND Xingnaojing injection (XNJi) is widely used for acute cerebral hemorrhage. However, the efficacy of XNJi for acute cerebral hemorrhage has not been comprehensively proved by systematic analysis yet. Therefore, it is essential to evaluate the efficacy and safety of XNJi in an evidence-based method. METHODS Six databases were searched with XNJi used for acute cerebral hemorrhage in randomized controlled trials (RCTs). Meta-analysis was performed by Review Manager 5.3. The efficacy rate, brain edema, cerebral hematoma, neurological deficit score, hs-crp, Glasgow Coma Scale (GCS), and activities of daily living (ADL) were systematically evaluated. The Cochrane risk of bias was used to evaluate the methodological quality of eligible studies. RESULTS This study is registered with PROSPERO (CRD42018098737). Twenty-nine studies with a total of 2638 patients were included in this meta-analysis. Compared with conventional treatment, XNJi got higher efficacy rate (OR = 3.37, 95% CI [2.65, 4.28], P < .00001). Moreover, XNJi showed significant enhancement of efficacy rate via subgroup analysis in course and dosage. In addition, XNJi demonstrated significant improvement in Chinese stroke scale (CSS) and National Institutes of Health Stroke Scale (NHISS) (mean difference [MD] = -4.74, 95% CI [-5.89, -3.60], P < .00001; MD = -4.45, 95% CI [-5.49, -3.41], P < .00001), GCS (MD = 2.72, 95% CI [2.09, 3.35], P < .00001). It also remarkably decreased the level of hs-crp (MD = -6.50, 95% CI [-7.79, -5.21], P < .00001), enhanced ADL (MD = 20.38, 95% CI [17.98, 22.79], P < .00001), and alleviated hematoma and edema (MD = -2.53, 95% CI [-4.75, -0.31] P < .05; MD = -1.74 95% CI [-2.42, -1.07] P < .00001) compared with conventional treatment. CONCLUSION XNJi is effective in treating acute cerebral hemorrhage with significant improvement of CSS, NHISS and impairment of hs-crp, hematoma, and edema compared with conventional treatment. Moreover, XNJi got remarkable efficacy at the dose of 20, 30, 60 mL and from 7 to 28 days. No serious adverse reactions occurred. These results were mainly based on small-sample and low-quality studies. Therefore, more rigorous, large-scale RCTs were further needed to confirm its efficacy, safety, and detailed characteristic of application.
The efficacy and safety of tranexamic acid in the treatment of intertrochanteric fracture: an updated meta-analysis of 11 randomized controlled trials
Journal of thrombosis and thrombolysis. 2020
This meta-analysis was performed to investigate the efficacy and safety of tranexamic acid (TXA) in the elderly patients undergoing intertrochanteric fracture surgery from the current literatures. The electronic literature database of PubMed, Embase and Cochrane library were searched in October 2019. The intraoperative blood loss, hidden blood loss, postoperative drainage and total blood loss, postoperative hemoglobin, length of stay, transfusion rate, mortality rate, thromboembolic events and wound complications were extracted. Stata 14.0 software was used for our meta-analysis. A total of 11 RCTs (3 new RCTs in 2019) with 1202 patients met our inclusion criteria. This meta-analysis showed that administration of TXA can reduce intraoperative blood loss (P = 0.009), hidden blood loss (P = 0.000), total blood loss (P = 0.000), length of stay (P = 0.003), transfusion rate (P = 0.000) and the occurrence of wound complications (P = 0.006). Furthermore, administration of TXA was associated with an increase in the postoperative Hb level at day 1, 2 and 3 (P = 0.000, P = 0.000 and P = 0.000, respectively) after surgery. However, no significant difference was found between the TXA group and control group regarding the occurrence of thromboembolic events (P = 0.978, including deep vein thrombosis, P = 0.850; pulmonary embolism, P = 0.788; cerebrovascular accident, P = 0.549; myocardial infarction, P = 0.395) and mortality rate (P = 0. 338). Our meta-analysis suggested that administration of TXA is effective in reducing intraoperative blood loss, hidden blood loss, total blood loss, length of stay, transfusion rate, wound complications and enhancing postoperative Hb without increasing the risk of thromboembolic events and mortality rate in intertrochanteric fracture surgery. More large multi-center and high-quality RCTs are required for further research.