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AIM: Describe the general situation of the First-In-Human trials of the drugs, and summarize the design and results of the First-In-Human trials. METHODS: We searched the literature of the First-In-Human trials in 2009-2020 on PubMed and screened out the literature that met the research purpose. The basic information of the literature was collected. Data analysis was conducted to summarize relevant outcomes. RESULTS: A total of 559 First-In-Human trials were included in this study. The types of drugs included small molecule drugs (52.42%, 293/559), macromolecule drugs (45.62%, 255/559), and a small amount of cells and viruses (1.97%, 11/559) and so on. Regarding the determination of the starting dose, whether it was in macromolecules (23.86%, 21/88) or small molecules (30.15%, 41/136), No Observed Adverse Effect Level (27.68%, 62/224) was mainly used as the main reference basis, followed by preclinical research (21.88%, 49/224) and Minimal Anticipated Biological Effect Level (8.48%, 19/224), etc. In the dose escalation test, 50.19%(135/269) of the studies used the traditional standard 3+3 dose escalation method, followed by the accelerated titration method (7.06%, 19/269), and the improved 3+3 method (6.69%, 18/269), etc. CONCLUSION: The design of First-In-Human clinical trials has certain regularity in the content and results of the research design. In the subsequent trials, it is important to scientifically design the First-In-Human trials, and promote the safe and effective development of the First-In-Human trials of the drugs.
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Objective:To explore the relationship among cardioversion ,cerebral infarction (CI) and N terminal pro brain natriuretic peptide (NT‐proBNP) level in patients with heart failure (HF) complicated atrial fibrillation (AF) . Methods :A total of 150 HF + AF patients received intravenous drip of amiodarone for cardioversion therapy .Ac‐cording to cardioversion results ,they were divided into cardioversion group (n=100 ) and non‐cardioversion group (n=50) ,NT‐proBNP level change was observed in two groups before and after cardioversion .According to CI on‐set or not ,patients were divided into CI group (n=20) and non‐CI group (n= 130) ,NT‐proBNP level was com‐pared between two groups before and after onset .Results :Within 48h after administration ,a total of 100 patients (66.67% ) recovered to sinus rhythm .Compared with before cardioversion ,NT‐proBNP level significantly reduced [(967.04 ± 366.16) pg/ml vs .(496.21 ± 142.54) pg/ml] after cardioversion in cardioversion group ,and was signifi‐cantly lower than that of non‐cardioversion group (996.76 ± 351.28) pg/ml , P<0.01 all . In CI group ,compared with small size CI group ,there were significant rise in NT‐proBNP level [ (784.21 ± 231.26) pg/ml vs .(1983.24 ± 32.96) pg/ml ,(3562.19 ± 1468.32) pg/ml] in medium and large size CI group , P< 0.05 or <0.01 .Conclusion:NT‐proBNP level at hospitalization possesses predictive value for drug cardioversion effect in HF + AF patients . NT‐proBNP level is related with CI onset .After acute CI ,the higher NT‐proBNP level is ,the larger infarct size is , the poorer prognosis is .