1.
CSL112 (Apolipoprotein A-I [Human]) Strongly Enhances Plasma Apoa-I and Cholesterol Efflux Capacity in Post-Acute Myocardial Infarction Patients: A PK/PD Substudy of the AEGIS-I Trial.
Gibson, CM, Kazmi, SHA, Korjian, S, Chi, G, Phillips, AT, Montazerin, SM, Duffy, D, Zheng, B, Heise, M, Liss, C, et al
Journal of cardiovascular pharmacology and therapeutics. 2022;:10742484221121507
Abstract
INTRODUCTION Cholesterol efflux capacity (CEC) is impaired following acute myocardial infarction (AMI). CSL112 is an intravenous preparation of human plasma-derived apoA-I formulated with phosphatidylcholine (PC). CSL112 is intended to improve CEC and thereby prevent early recurrent cardiovascular events following AMI. AEGIS-I (ApoA-I Event Reducing in Ischemic Syndromes I) was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging phase 2b study, designed to evaluate the hepatic and renal safety of CSL112. Here, we report an analysis of a pharmacokinetic (PK) and pharmacodynamic (PD) substudy of AEGIS-I. METHODS AMI patients were stratified by renal function and randomized 3:3:2 to 4, weekly, 2-hour infusions of low- and high-dose (2 g and 6 g) CSL112, or placebo. PK/PD assessments included plasma concentrations of apoA-I and PC, and measures of total and ABCA1-dependent CEC, as well as lipids/lipoproteins including high density lipoprotein cholesterol (HDL-C), non-HDL-C, low density lipoprotein cholesterol (LDL-C), ApoB, and triglycerides. Inflammatory and cardio-metabolic biomarkers were also evaluated. RESULTS The substudy included 63 subjects from AEGIS-I. CSL112 infusions resulted in rapid, dose-dependent increases in baseline corrected apoA-I and PC, which peaked at the end of the infusion (Tmax ≈ 2 hours). Similarly, there was a dose-dependent elevation in both total CEC and ABCA1-mediated CEC. Mild renal impairment did not affect the PK or PD of CSL112. CSL112 administration was also associated with an increase in plasma levels of HDL-C but not non-HDL-C, LDL-C, apoB, or triglycerides. No dose-effects on inflammatory or cardio-metabolic biomarkers were observed. CONCLUSION Among patients with AMI, impaired CEC was rapidly elevated by CSL112 infusions in a dose-dependent fashion, along with an increase in apoA-I plasma concentrations. Findings from the current sub-study of the AEGIS-I support a potential atheroprotective benefit of CSL112 for AMI patients.
2.
Lenvatinib versus sorafenib for unresectable hepatocellular carcinoma: a cost-effectiveness analysis.
Cai, H, Zhang, L, Li, N, Zheng, B, Liu, M
Journal of comparative effectiveness research. 2020;(8):553-562
Abstract
Aim: To investigate the cost-effectiveness of lenvatinib and sorafenib in the treatment of patients with nonresected hepatocellular carcinoma in China. Materials & methods: Markov model was used to simulate the direct medical cost and quality-adjusted life years (QALY) of patients with hepatocellular carcinoma. Clinical data were derived from the Phase 3 randomized clinical trial in a Chinese population. Results: Sorafenib treatment resulted in 1.794 QALYs at a cost of $43,780.73. Lenvatinib treatment resulted in 2.916 QALYs for patients weighing <60 and ≥60 kg at a cost of $57,049.43 and $75,900.36, The incremental cost-effectiveness ratio to the sorafenib treatment group was $11,825.94/QALY and $28,627.12/QALY, respectively. Conclusion: According to WHO's triple GDP per capita, the use of lenvatinib by providing drugs is a cost-effective strategy.
3.
Vitamin D supplementation prior to in vitro fertilisation in women with polycystic ovary syndrome: a protocol of a multicentre randomised, double-blind, placebo-controlled clinical trial.
Hu, KL, Gan, K, Wang, R, Li, W, Wu, Q, Zheng, B, Zou, L, Zhang, S, Liu, Y, Wu, Y, et al
BMJ open. 2020;(12):e041409
Abstract
INTRODUCTION Polycystic ovary syndrome (PCOS) is one of the leading causes of female infertility, affecting around 5% of women of childbearing age in China. Vitamin D insufficiency is common in women with PCOS and is associated with lower live birth rates. However, evidence regarding the effectiveness of vitamin D supplementation in women with PCOS is inconclusive. This multicentre randomised, double-blinded, placebo-controlled trial aims to evaluate the effectiveness of vitamin D supplementation prior to in vitro fertilisation (IVF) on the live birth rate in women with PCOS. METHODS AND ANALYSIS We plan to enrol women with PCOS scheduled for IVF. After informed consent, eligible participants will be randomised in a 1:1 ratio to receive oral capsules of 4000 IU vitamin D per day or placebo for around 12 weeks until the day of triggering. All IVF procedures will be carried out routinely in each centre. The primary outcome is live birth after the first embryo transfer. The primary analysis will be by intention-to-treat analysis. To demonstrate or refute that treatment with vitamin D results in a 10% higher live birth rate than treatment with placebo, we need to recruit 860 women (48% vs 38% difference, anticipating 10% loss to follow-up and non-compliance, significance level 0.05 and power 80%). ETHICS AND DISSEMINATION This study has been approved by the Ethics Committee in Women's Hospital of Zhejiang University on 2 March 2020 (reference number: IRB-20200035-R). All participants will provide written informed consent before randomisation. The results of the study will be submitted to scientific conferences and a peer-reviewed journal. TRIAL REGISTRATION NUMBER NCT04082650.
4.
A randomized, controlled clinical trial on meropenem versus imipenem/cilastatin for the treatment of bacterial infections.
Hou, F, Li, J, Wu, G, Zheng, B, Chen, Y, Gu, J, Wang, H, Huo, L, Xue, X, Jia, C, et al
Chinese medical journal. 2002;(12):1849-54
Abstract
OBJECTIVE To evaluate the efficacy and safety of meropenem in Chinese patients, we conducted a study for the treatment of patients with lower respiratory tract infections, urinary tract infections and other infections. METHODS A total of 182 hospitalized patients were enrolled in the study. 90 patients received 500 mg meropenem every 12 hours (or 1 g every 12 hours if necessary) and 92 patients received imipenem/cilastatin 500 mg/500 mg every 12 hours (or 1 g every 12 hours if necessary) by intravenous infusion. The duration of treatment was 7 - 14 days for both groups. RESULTS Seventy of 90 cases receiving meropenem and 70 of 92 cases receiving imipenem/cilastatin were assessable for clinical efficacy. The overall efficacy rates were 90% for the meropenem group and 87% for the imipenem/cilastatin group, and the bacterial eradication rates were 86% in both groups. 93 (76%) of 123 strains isolated from patients produced beta-lactamases. Adverse drug reactions were evaluated in 72 cases in the meropenem group and 70 cases in the imipenem/cilastatin group. The adverse drug reaction rates were 9.7% and 8.6%, respectively. The results showed that there were no statistical differences between these two groups (P > 0.05). CONCLUSION Meropenem is effective and safe for the treatment of bacterial infections caused mainly by beta-lactamase-producing strains.