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.
Anticoagulation treatment for patients with coronavirus disease 2019 (COVID-19) and its clinical effectiveness in 2020: A meta-analysis study
BACKGROUND To better inform efforts to treat and control the current outbreak with effective anticoagulant treatment strategies for coronavirus disease 2019 patients. METHODS We searched Cochrane Library, Pubmed, EMBASE, MEDLINE, SCIEXPANDED, Web of Science, Google Scholar, CNKI (Chinese Database), WanFang (Chinese Database), CBM (Chinese Database), VIP (Chinese Database) for studies published from November 1, 2019 to October 1, 2020, and we searched references of identified articles. Studies were reviewed for methodological quality. A random-effects model was used to pool results. Heterogeneity was assessed using I2. Publication bias was assessed using funnel plot. RESULTS Fourteen studies involving 7681 patients were included. We meta-analyzed the bleeding, deep vein thrombosis, and pulmonary embolism risk between no anticoagulation and prophylactic anticoagulation, and found no significant difference. The same trend occurred in the comparison between with and without anticoagulation. However, when compared with no anticoagulation, both prophylactic anticoagulation (odd ratio [OR] = 0.80, 95% confidence interval [CI]: 0.69-0.93) and therapeutic anticoagulation (OR = 0.91, 95% CI: 0.80-1.05) had lower risk of mortality. Furthermore, the risk of overall bleeding among patients with therapeutic anticoagulation was 3.11 times (95% CI: 2.29-4.24) than that of patients with prophylactic anticoagulation. On the contrary, therapeutic anticoagulation had lower risk of deep vein thrombosis than prophylactic anticoagulation (OR = 0.34, 95% CI: 0.19-0.63). CONCLUSIONS Among coronavirus disease 2019 patients, preventive and therapeutic anticoagulation were more beneficial than no anticoagulation for reducing mortality rate. The result will inform healthcare providers and public health policy makers in efforts to treat and control the current outbreak.
Efficacy and safety of eltrombopag in Chinese patients with chronic immune thrombocytopenia: stage 2 results from a multicenter phase III study
This phase III, randomized, placebo-controlled study conducted in three stages (6-week, randomized, placebo-controlled stage 1; 24-week, open-label stage 2; and continuous extension stage 3) assessed the long-term efficacy and safety of eltrombopag use in Chinese patients with chronic immune thrombocytopenia (ITP). This article presents the results from stage 2. Overall, 150 patients (placebo-eltrombopag [P-E], 50; eltrombopag-eltrombopag [E-E], 100) received open-label eltrombopag. The median platelet count was maintained between 41 × 10(9)/L and 80 × 10(9)/L. Most patients in both groups (P-E, 90.0%; E-E, 81.8%) achieved platelet counts ≥30 × 10(9)/L and ≥2 times the baseline platelet count at least once with eltrombopag treatment. Overall, 32% of patients achieved platelet counts ≥50 × 10(9)/L in ≥75% of platelet count assessments. Both groups showed a decreased tendency to infrequent bleeding and clinically significant bleeding events during stage 2 compared with baseline. Among patients who received ≥1 ITP medication at baseline, 70.4% in the P-E group and 40.8% in the E-E group reduced or permanently stopped ≥1 of their ITP medications. The stage 2 results further demonstrated a sustainable long-term efficacy and good tolerability of eltrombopag with a favorable benefit-risk ratio in Chinese chronic ITP patients. Trial registration: Clinicaltrials.gov NCT01762761. Registered 8 January 2013, https://clinicaltrials.gov/ct2/show/NCT01762761.
Effect of tranexamic acid on symptomatic venous thromboembolism in patients undergoing primary total knee arthroplasty
Arch Med Sci. 2020;16(3):603-612
Introduction: This study aimed to investigate the effect of tranexamic acid (TXA) with sequential routine anticoagulation on postoperative symptomatic venous thromboembolism (VTE) in patients undergoing primary total knee arthroplasty (TKA). Material and methods: This was a prospective study with randomized trials. From January 2013 to May 2015, 1880 patients undergoing primary TKA were enrolled in this study. Seven hundred and twenty patients who received TXA injection were included in the TXA group while 1160 patients who received placebo injection were included in the control group. Patients in the TXA group were treated with intravenous TXA or topical intravenous TXA, and all received sequential routine anticoagulation 12 h after the operation. We extracted data of patients' sex, age, primary diagnoses, and comorbidities that could potentially affect the prevalence rate of VTE. To discuss the risk factors of symbolic VTE, comparisons were made within the TXA group between patients with symbolic VTE and non-symbolic VTE. Logistic regression analysis was performed to analyze the concurrent effects of various factors on the prevalence rate of postoperative VTE. Results: Thigh perimeter was not closely associated with TXA injection. Within the TXA group, 24 (3.3%) patients had perioperative symptomatic VTE, 16 (2.2%) deep vein thrombosis (DVT) and 8 (1.1%) pulmonary embolism. High body mass index (BMI), low fibrinogen (Fbg) and simultaneous bilateral TKA were significant risk factors in both univariate analysis and multivariate analysis. Conclusions: Increased BMI, low Fbg, and simultaneous bilateral TKA could act as risk factors for postoperative symptomatic VTE treated with TXA.
Effect of deferasirox + erythropoietin vs erythropoietin on erythroid response in Low/Int-1-risk MDS patients: Results of the phase II KALLISTO trial
European Journal of Haematology. 2018
OBJECTIVES Erythropoiesis-stimulating agents (ESAs) remain first-choice to treat symptomatic anemia and delay transfusion dependence in most patients with lower-risk myelodysplastic syndromes (MDS) without del(5q). Deferasirox increased erythroid responses in some lower-risk MDS patients in clinical trials, and adding low-dose deferasirox to ESA treatment may further improve erythroid response. METHODS KALLISTO (NCT01868477) was a randomized, open-label, multicenter, phase II study. Lower-risk MDS patients received deferasirox at 10 mg/kg/day (dispersible tablets) or 7 mg/kg/day (film-coated tablets) plus erythropoietin (n=11), or erythropoietin alone (n=12) for 24 weeks. The primary endpoint was the between-group difference in erythroid response within 12 weeks. RESULTS Erythroid response occurred in 27.3% of patients receiving deferasirox plus erythropoietin versus 41.7% of patients receiving erythropoietin alone within 12 weeks (difference 14.4%; 95% CI -24.0, 48.16). Within 24 weeks, the hematologic response rate was 27.3% with deferasirox plus erythropoietin versus 50% with erythropoietin alone, and hematologic improvement rates were 45.5% versus 100%. Deferasirox plus erythropoietin was generally well tolerated. CONCLUSIONS In this small pilot study, combining low-dose deferasirox with erythropoietin did not improve erythroid response. It remains of interest to investigate early chelation approaches with even lower deferasirox doses plus erythropoietin in lower-risk MDS patients before the onset of transfusion dependence. KEY WORDS Deferasirox, erythropoietin, myelodysplastic syndromes, anemia, therapy, hematologic response, erythroid response, clinical trials This article is protected by copyright. All rights reserved.
Multicentre, randomised phase III study of the efficacy and safety of eltrombopag in Chinese patients with chronic immune thrombocytopenia
British Journal of Haematology. 2016;176((1):):101-110
Eltrombopag, a thrombopoietin receptor agonist, raises platelet counts and reduces bleeding in patients with immune thrombocytopenia (ITP). In Chinese patients, eltrombopag was evaluated at an initial dose of 25 mg, vs. 50 mg for non-Asians, because the plasma exposure of eltrombopag is higher in East Asians. A multicentre, double-blind, randomised, placebo-controlled, 8-week, phase III study enrolled 155 patients with chronic, previously treated ITP. Dosage could be adjusted (25-75 mg/day) to maintain platelet counts 50-250 x 109 /l. The primary efficacy endpoint was the proportion of patients with a platelet count ≥50 x 109 /l after Day 42. Pharmacokinetics and pharmacodynamics of eltrombopag were analysed in an open-label extension. After Day 42, 57.7% of eltrombopag-treated and 6.0% of placebo-treated patients achieved platelet counts ≥50 x 109 /l. Odds of achieving a platelet count ≥50 x 109 /l were 26.08 times greater with eltrombopag than placebo (P < 0.001). Compared with placebo, time to response and duration of response were better with eltrombopag (P < 0.001) and the odds of any bleeding were reduced by 72% (P = 0.001). Tolerability, pharmacokinetics, and pharmacokinetics/pharmacodynamics were similar to previous findings in East Asian patients. In conclusion, in Chinese patients with chronic ITP, eltrombopag 25 mg once daily, elevated platelet counts to a safe range and reduced bleeding.
Effect of eltrombopag on platelet response and safety results in Chinese adults with chronic ITP - primary result of a phase III study
Blood. 2014;124((21)): Abstract No. 1464
Prevention of HLA antibody formation in patients with hemato-oncologic diseases by using leukocyte depleted blood preparations German
Infusionstherapie und Transfusionsmedizin. 1995;22((1):):9-13.
OBJECTIVE To determine the effect of transfusion therapy with leukocyte-depleted platelet concentrates in comparison to transfusion support with standard platelet concentrates on the frequency of HLA alloimmunization in hematologic-oncologic patients. DESIGN Prospective randomized study. SETTING Institute for Transfusion Medicine and Immunohematology at a University Hospital. PATIENTS 52 hematologic-oncologic patients randomized in 2 groups. INTERVENTIONS Exclusive substitution with leukocyte-depleted blood components (platelet concentrates and packed red cells, filter group) or with standard platelet concentrates and leukocyte-depleted packed red cells (control group). Determination of the development of HLA antibodies. RESULTS 27% of the patients in the control group (4 out of 15) developed HLA antibodies in contrast to zero patients (0 out of 22) in the filter group (p < 0.02). CONCLUSIONS The results of this comparative clinical study show that the consequent and exclusive support with leukocyte-depleted blood components is an effective approach for prevention of HLA alloimmunization in long-term substituted patients.