Clinical trials

Tuberculosis (TB) remains a major public health issue and one of the top ten causes of death from a single infectious disease worldwide. China is among the countries with the highest TB burden, ranking third globally for total TB cases and second for drug-resistant TB cases. PAN-TB is an innovative concept in TB treatment, aiming to develop a universal regimen effective for all forms of active TB, including both drug-susceptible and drug-resistant strains. The primary goal of the PAN-TB regimen is to simplify the treatment process, reduce costs, and improve treatment success rates. The ideal Target Regimen Profile (TRP) for PAN-TB includes superior efficacy compared to standard treatment for non-drug-resistant TB, a reduced treatment duration from the current 4-6 months to 2-3 months, and improved safety and tolerability. This project aims to explore a new ultra-short-course treatment regimen for both drug-sensitive (DS-TB) and drug-resistant TB (MDR/RR-TB), which aligns with the latest trends in TB treatment both domestically and internationally. The regimen also has significant practical implications for enhancing treatment efficacy and reducing patient burden. Furthermore, the study will explore the identification of new biomarkers closely linked to treatment outcomes over the course of full-cycle therapy.

The goal of this clinical trial is to learn if peginterferon alfa-2b can reduce the recurrence of HBV-related liver cancer in patients who have undergone radical treatment. The study will also explore the potential benefits of peginterferon alfa-2b in achieving clinical cure and its impact on reducing liver cancer recurrence. The trial is designed as a single-center, non-randomized, open-label study. Participants will be HBV-related liver cancer patients who have received radical treatment. The study will compare two groups: one receiving nucleos(t)ide analogues (NAs) alone and the other receiving NAs combined with peginterferon alfa-2b. The main question it aims to answer is: Can peginterferon alfa-2b lower the 3-year recurrence rate in HBV-related liver cancer patients after radical treatment? Participants will undergo regular follow-ups, including imaging studies and blood tests, to monitor for cancer recurrence and assess the safety of the treatment.

Tuberculosis (TB) remains one of the leading global public health concerns and is among the top ten causes of death from a single infectious agent. China ranks third worldwide in total TB burden, with a substantial proportion of cases classified as drug-susceptible TB (DS-TB). Despite the availability of effective standard treatment regimens, the current 6-month therapy duration poses challenges in terms of patient adherence, resource allocation, and overall treatment success. In recent years, ultrashort-course regimens for DS-TB have been proposed and evaluated in clinical studies, showing promising results in improving adherence, reducing treatment duration, and maintaining or even enhancing treatment efficacy. However, these regimens have primarily been studied in younger populations, with limited data available for elderly patients. Older adults often present with age-related physiological changes, multiple comorbidities, and an increased risk of adverse drug reactions, which may affect both the efficacy and safety of treatment. Therefore, this study aims to assess the therapeutic effectiveness and safety profile of a novel ultrashort-course regimen for drug-susceptible pulmonary TB specifically in patients aged 65 years and older.

Background Chronic hepatitis B (CHB) is a global health issue that affects a large number of patients. There is currently controversy regarding the treatment strategies for CHB patients with metabolic-associated steatoliver disease (MASLD). Therefore, this study aims to conduct a prospective cohort study to compare the therapeutic effects of pegylated interferon α-2b (Peg IFNα-2b) combined with nucleos(t)ide analogues (NAs) in CHB patients with and without MASLD, and to explore the metabolic improvement effects of Peg IFNα-2b treatment in CHB patients with MASLD. Design This study is a single-center, non-randomized controlled clinical trial. The subjects are CHB patients planned to receive Peg IFNα-2b combined with NAs, who will be naturally divided into two groups based on the presence or absence of MASLD. The study period is from September 15, 2024, to December 31, 2029, with a planned enrollment of 830 patients. Methods Inclusion Criteria: Adults aged 18 to 65 years, with HBsAg positivity for more than 6 months, HBeAg negativity, HBsAg level ≤1500 IU/ml, ALT \<10 ULN (400 IU/L), no interferon treatment in the past year, and signed informed consent. Grouping Criteria: Patients will be divided into two groups based on the presence or absence of MASLD. MASLD is defined by hepatic steatosis confirmed by imaging or liver biopsy, and the presence of at least one of the following five metabolic factors: BMI ≥23 or waist circumference exceeding the standard, abnormal blood glucose, blood pressure ≥130/85 mmHg, plasma triglycerides ≥1.70 mmol/L, and abnormal plasma high-density lipoprotein cholesterol. Exclusion Criteria: Pregnant or breastfeeding patients, heavy drinkers, patients with HIV infection, co-infected with other viral hepatitis, patients with liver cirrhosis or hepatocellular carcinoma, severe cardiocerebrovascular or renal diseases, psychiatric abnormalities, abnormal peripheral blood leukocytes or platelet count, interferon allergy, etc. Withdrawal Criteria: Patients who withdraw informed consent, request to exit, experience severe adverse events, have serious protocol violations, become pregnant, have poor compliance, are lost to follow-up, or whose continued participation in the study is deemed unsafe by the investigator. Research Endpoints Primary Endpoint: HBsAg clearance rate at 48 weeks of treatment. Secondary Endpoints: Proportion and baseline reduction of HBsAg \<1500 IU/ml at the end of treatment, reduction of HBV DNA levels from baseline and proportion below the detection limit, clearance and seroconversion rates of HBeAg in HBeAg-positive patients, and the incidence of cardiovascular disease in MASLD patients at the end of treatment. Conclusion This study aims to provide evidence for the individualized treatment of CHB patients with MASLD, clarify the impact of MASLD on the treatment response of CHB patients, optimize treatment protocols, increase clinical cure rates, and explore new strategies for improving patients' metabolic functions. Through this study, we hope to provide more precise decision-making support for clinicians, thereby improving patients' quality of life and long-term prognosis.

\*\*Document Name: This Trial is a Phase II Clinical Study.docx\*\* \*\*Document Content:\*\* * This trial is a Phase II clinical study, conducted in two stages: * \*\*Phase IIa:\*\* A sentinel, single-arm design will be employed. A total of 12 early ACLF subjects are expected to be enrolled in the 0.5 mg/kg dose group. The first 2 subjects will serve as sentinels and be enrolled sequentially to receive a single intravenous dose. If no drug-related SAEs (Serious Adverse Events) occur in these 2 sentinel subjects within 2 weeks after the first dose, the remaining 10 subjects will be enrolled. Otherwise, the dose will be reduced for further exploration. After receiving a single intravenous dose, subjects will undergo a 20-day washout period. If no drug-related ≥Grade 3 AEs (Adverse Events) occur during this 20-day washout period, and safety/tolerability is jointly confirmed by the investigator and sponsor, the subject will enter the multiple-dose phase (once weekly \[Day 21 as the first dose of multiple administration\], for 4 consecutive weeks). If any drug-related ≥Grade 3 AE occurs, the dose will be reduced for further exploration, with the specific dose determined by the sponsor and investigator. If a subject drops out during the washout period after a single dose, additional subjects may be enrolled to ensure at least 12 subjects enter the multiple-dose phase. * After all 12 early ACLF subjects in the 0.5 mg/kg dose group complete continuous dosing, the DMC (Data Monitoring Committee) will assess the safety of this dose group. If any of the following occur in the 0.5 mg/kg group, the DMC will discuss whether to proceed with dose escalation: \> 1) ≥1/3 of subjects experience drug-related Grade 3 SAEs; \> 2) Any drug-related Grade 4 or higher SAEs. * If the DMC determines that dose escalation criteria are met, an additional 12 early ACLF subjects will be enrolled to receive the 1 mg/kg dose group. The same enrollment rules as the 0.5 mg/kg group apply: the first 2 subjects are sentinels receiving a single intravenous dose. If no drug-related SAEs occur in these sentinels within 2 weeks post-dose, the remaining 10 subjects will be enrolled. Post-single-dose administration, subjects will undergo a 20-day washout period. If no drug-related ≥Grade 3 AEs occur during this period, and safety/tolerability is confirmed, subjects will enter the multiple-dose phase (once weekly \[Day 21 as the first dose\], for 4 consecutive weeks). Dropouts during the washout period may be replaced to ensure at least 12 subjects enter the multiple-dose phase. * After completing the 0.5 mg/kg and 1 mg/kg dose exploration studies, the investigator and sponsor may determine the recommended dose for Phase IIb based on cumulative safety, efficacy, and potential PK/PD results. Additional dose groups or alternative administration frequencies may also be explored. * \*\*Phase IIb:\*\* A randomized (1:1), double-blind, placebo-controlled design will be used. A total of 72 ACLF subjects are expected to receive either AS1501 at the appropriate dose/frequency or placebo to further evaluate the efficacy and safety of AS1501 injection. The specific design will be finalized based on Phase IIa results and agreed upon by the investigator and sponsor.

Infection post liver transplantation is an important factor in the death in patients. The traditional method of diagnosing infection post liver transplantation is laboratory tests. But the sensitivity and specificity of blood tests is poor. Next-generation sequencing (NGS) has greater detection rate for mycobacterium tuberculosis, anaerobes and fungi and greater sensitivity compare with blood tests. However use of NGS is limited because of the short read-length. Oxford nanopore adaptive sequencing (NAS) method is the Third Revolution in Sequencing Technology. For each 1 Gbp of data, NAS sequencing detected 45 times more microbiome sequences than Nanopore standard sequencing and 2.5 times more than Illumina sequencing. The purpose of this study is to compare NAS with NGS and laboratory tests for the diagnostic rate of infection post liver transplantation.

Short PIVC (intravenous indentation needle) accounts for more than 50% of clinical infusion tools, but long PIVC is rarely used and studied in China. This study aims to explore the application characteristics and application effects of long PIVC in China. It provides reference for the correct selection of infusion tools, and promotes the clinical application and promotion of new intravenous therapy tools. The study nurse will work with the responsible physician to assess the eligibility for enrollment and sign the informed consent. Were randomly assigned to the control group (to receive a new 24G/22G (0.7mm\*19mm/0.9mm\*25mm) short PIVC (closed needle protected venous catheter system) puncture) or the intervention group (to insert a new 3F (8cm) or 4F(10cm) long PIVC) for daily routine maintenance until catheter removal, General demographic data, laboratory-related data, catheter-related data, catheter-related complications (unplanned extubation, phlebitis, catheter blockage, catheter-related thrombosis, catheter-related bloodstream infection, exudation, etc.) and patient satisfaction were collected.

Liver transplantation is the most efficacious treatment for end-stage liver disease; however, postoperative infection remains a major complication and leading cause of recipient mortality. Specifically, infections originating from donors, particularly those caused by multidrug-resistant bacteria, can significantly impact the prognosis of liver transplant recipients. Theoretically, implementing targeted antimicrobial therapy for donors prior to organ donation could reduce the likelihood of pathogen transmission with the transplanted organ, thereby potentially decreasing the incidence of post-transplant infections from donor sources and improving recipient outcomes. Nevertheless, there is currently a dearth of high-quality prospective studies in this domain. Our previous investigation (Front Microbiol. 2022 Jul 1;13:919363) demonstrated that second-generation metagenomic sequencing (mNGS) technology holds substantial value in expeditious pathogen screening following liver transplantation. Prompt implementation of targeted treatment based on microbiological findings has shown potential to enhance outcomes for select recipients. Therefore, this study aims to provide tailored treatment for donors based on microbiological examination results (including mNGS detection and culture results), analyze corresponding data regarding recipient infection occurrence and prognosis, and explore the impact of mNGS-guided donor antimicrobial therapy on perioperative infection rates among liver transplant recipients.