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.
Restrictive versus liberal strategy for red blood-cell transfusion in hip fracture patients: A systematic review and meta-analysis
BACKGROUND Most clinical guidelines recommend a restrictive red-blood-cell (RBC) transfusion threshold. However, indications for transfusion in patients with a hip fracture have not been definitively evaluated or remain controversial. We compared the pros and cons of restrictive versus liberal transfusion strategies in patients undergoing hip fracture surgery. METHODS Electronic databases were searched to identify randomized controlled trials (RCTs) and retrospective cohort studies (RCSs) to investigate the effects of a restrictive strategy versus its liberal counterpart in patients undergoing hip fracture surgery. The main clinical outcomes included delirium, mortality, infections, cardiogenic complications, thromboembolic events, cerebrovascular accidents, and length of hospital stay. The meta-analysis program of the Cochrane Collaboration (RevMan version 5.3.0) was used for data analysis. Statistical heterogeneity was assessed by both Cochran chi-squared test (Q test) and I test. Both Begg and Egger tests were used to assess potential publication bias. RESULTS We identified 7 eligible RCTs and 2 eligible RCSs, involving 3,575 patients in total. In patients undergoing hip fracture surgery, we found no differences in frequency of delirium, mortality, the incidence rates of all infections, pneumonia, wound infection, all cardiovascular events, congestive heart failure, thromboembolic events or length of hospital stay between restrictive and liberal thresholds for RBC transfusion (P >.05). However, we found that the use of restrictive transfusion thresholds is associated with higher rates of acute coronary syndrome (P <.05) while liberal transfusion thresholds increase the risk of cerebrovascular accidents (P <.05). CONCLUSION In patients undergoing hip fracture surgery, clinicians should evaluate the patient's condition in detail and adopt different transfusion strategies according to the patient's specific situation rather than merely using a certain transfusion strategy.
Venous thromboembolism risk and erythropoiesis-stimulating agents for the treatment of cancer-associated anemia: a meta-analysis
Tumour Biology. 2014;35((1):):603-13.
Erythropoiesis-stimulating agents (ESAs) reduce anemia in patients with cancer and could improve their quality of life, but ESA-related safety concerns exist. To evaluate the overall risk of venous thromboembolism (VTE) associated with the use of ESAs, a systematic review and meta-analysis of published randomized controlled trials (RCTs) was performed. The databases of PubMed and Web of Science and the abstracts presented at the American Society of Clinical Oncology conferences were searched to identify relevant clinical trials. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated. A total of 12,115 patients with a variety of cancer types from 51 RCTs were identified and included in the meta-analysis. Among patients receiving ESAs, the summary incidence of all-grade VTE was 7.78%. Patients with cancer who received ESAs had increased VTE risks (484 events among 6,301 patients treated with ESA vs. 276 events among 5,814 control patients; RR=1.75 [95% CI, 1.50-2.05]). The highest risk of VTE was found in patients with ovarian and cervical cancers (RR=2.45 [CI=1.12-5.33]). The VTE risk among hematologic malignancies was higher than that among solid tumors. The administration of ESAs was significantly associated with an increased risk of developing VTE in cancer patients receiving these drugs. The risks of VTE may vary with various tumor types, including hematologic malignancies.