Ignite Creation Date:
2024-10-25 @ 7:48 PM
Last Modification Date:
2024-10-26 @ 3:37 PM
Study NCT ID:
NCT06539455
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
None
First Post:
2024-07-30
Brief Title:
Analysis of Liver Injury Risk Factors in a Multiethnic Population Treated With Antituberculosis Drugs
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Analysis of Liver Injury Risk Factors in a Multiethnic Population Treated With Antituberculosis Drugs
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TUBILI
Brief Summary:
Tuberculosis TB is the worlds second leading cause of death from a single infectious agent after COVID-19 In 2022 TB was estimated to have affected 106 million people of whom 13 million died because of it despite the WHOs implementation of the End TB program Although the gold standard therapy is effective it may lead to adverse events among which hepatotoxicity is the most common Due to its frequency severity and potential outcome anti-TB drug-induced liver injury DILI is extremely concerning Despite decades of use and the large number of patients exposed to anti-TB drugs worldwide the pathogenesis underlying DILI remains poorly understood Investigation of drug-related host genetic and environmental factors associated with hepatotoxicity susceptibility as well as studies examining potential mechanisms causing DILI may help clinicians develop strategies for reducing the incidence of hepatotoxicity The aim of this study was to determine host- and drug-related risk factors and their association with hepatotoxicity in a multiethnic population in order to enable early identification of individuals with increased susceptibility to anti-TB DILI An improved understanding of these factors may help to predict and prevent the occurrence of DILI and develop more effective treatments
Detailed Description:
Tuberculosis TB is the worlds second leading cause of death from a single infectious agent in 2022 after COVID-19 In 2022 TB disease was estimated to affect 106 million people of whom 13 million died because of it despite the WHOs adoption of the End TB Strategy The standardised therapy involves a treatment regimen of isoniazid INH rifampin RIF ethambutol EMB and pyrazinamide PZA for 2 months then INH and RMP for at least an additional 4-7 months 3 Even though 85 of TB cases are successfully treated significant morbidity from treatment-related adverse events such as hepatotoxicity skin reactions and gastrointestinal and neurological disorders reduces the efficacy of therapy In 11 of patients receiving INH RMP and PZA in combination hepatotoxicity is the most frequent adverse effect that results in drug discontinuation One of the most prevalent subtypes of idiosyncratic hepatotoxicity is caused by anti-TB drugs There are many factors contributing to the development of liver injury that are related both to the drug and to the patients characteristics As to drug-related factors acetylhydrazine which is generated by NAT2 is widely considered a crucial INH metabolite that contributes to drug-induced liver injury DILI Given the importance of acetylation in INH metabolism several studies have investigated NAT2 loss of function polymorphisms as possible risk factors for anti-TB DILI In addition advanced age female gender poor nutritional status HBV or HCV infection HIV infection chronic liver disease and alcoholism are environmental physiological and pathological factors contributing to anti-TB DILI incidence Geographic and ethnic characteristics also play a role in the occurrence of DILI This event is also ascribed to the polymorphisms observed at the level of genes encoding for metabolic enzymes Of note most studies available in the literature have been conducted in Asiatic geographical areas where TB is considered of great concern due to its high incidence Moreover it is well known that the Chinese population is commonly composed of NAT2 rapid acetylators showing a lower susceptibility to the development of anti-TB DILI There is still considerable controversy and uncertainty regarding the potential role that the acetylator status of individuals rapid or slow may play in INH-induced hepatotoxicity given the fact that the results of previous studies have shown such considerable variability
Due to the impossibility of treating liver injury the only recovery strategy is drug discontinuation in tuberculosis patients its prevention is essential to avoiding this condition To prevent the progression of the disease increase the efficiency of treatment and reduce mortality screening patients for risk factors may be extremely useful Consequently the current studys aim is to determine the association between anti-TB DILI incidence and potential environmental physiologic and pathologic factors Since 2020 a cohort of patients has been followed in the Department of Infectious Diseases of Luigi Sacco Hospital in Milan Italy Moreover despite the multi-ethnic characterisation of the cohort enrolled in this study the high prevalence of Caucasian patients who also present a greater frequency of slow acetylators may be provide a complementary perspective to previously published studies mostly focusing on Asian populations Based on this cohort we performed a nested case-control study to understand the role of several drug- and host-related factors in DILI
Due to the impossibility of treating liver injury the only recovery strategy is drug discontinuation in tuberculosis patients its prevention is essential to avoiding this condition To prevent the progression of the disease increase the efficiency of treatment and reduce mortality screening patients for risk factors may be extremely useful Consequently the current studys aim is to determine the association between anti-TB DILI incidence and potential environmental physiologic and pathologic factors Since 2020 a cohort of patients has been followed in the Department of Infectious Diseases of Luigi Sacco Hospital in Milan Italy Moreover despite the multi-ethnic characterisation of the cohort enrolled in this study the high prevalence of Caucasian patients who also present a greater frequency of slow acetylators may be provide a complementary perspective to previously published studies mostly focusing on Asian populations Based on this cohort we performed a nested case-control study to understand the role of several drug- and host-related factors in DILI
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None