The goal of this clinical trial is to evaluate if N-acetylcysteine (NAC) works to prevent post-tuberculosis lung disease (PTLD) in patients with severe pulmonary impairment. It also aims to assess the safety of NAC. The main questions the study aims to answer are: Does NAC improve lung function (FEV1%) over 12 months in participants with pulmonary tuberculosis and baseline risk factors for PTLD? What medical issues or adverse events do participants experience while taking NAC? Researchers will compare NAC treatment to a control group to see if it can prevent PTLD when given in addition to standard TB treatment. Participants will: Take NAC (1800mg twice daily) for 6 months with standard TB treatment or receive standard TB treatment alone; Attend scheduled clinic visits for 12 months, during which they will have respiratory assessments, blood tests, and symptom monitoring; Complete quality-of-life questionnaires and provide sputum and blood samples for analysis at multiple time points.
Study Summary: This prospective, randomized, controlled, parallel-arm, open-label clinical trial evaluates the efficacy of N-acetylcysteine (NAC) as an adjunctive therapy for persons with pulmonary tuberculosis and risk factors for PTLD. The study aims to determine the long-term impact of NAC on lung function, respiratory symptoms, and quality of life in patients with drug-sensitive, culture-confirmed pulmonary tuberculosis (TB). Study Rationale: Pulmonary TB is a leading cause of chronic lung impairment globally. PTLD results in significant morbidity even after successful TB treatment. Prior research suggests NAC may mitigate oxidative stress and preserve lung function in TB patients. This trial seeks to confirm and expand findings from the NAC-TB sub-study of TB Sequel regarding PTLD prevention and treatment. This trial aims to provide robust evidence on the role of NAC in PTLD management, potentially informing future TB treatment guidelines.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
SINGLE
Enrollment
242
NAC will be provided as 600 mg capsules from NOW Healthgroup. Standard TB treatment will be provided as fixed dose combination tablets.
Standard TB treatment will be provided as fixed dose combination tablets.
MRC Unit The Gambia at LSHTM
Fajara, The Gambia, The Gambia
RECRUITINGFEV1% of predicted at month 12
Measured by spirometry
Time frame: month 12
FEV1%
FEV1%, at other time points and as summary measures over time
Time frame: Through study completion, an average of 12 months
FVC%
FVC%, at other time points and as summary measures over time using mixed effects modeling;
Time frame: Through study completion, an average of 12 months
FEV/FVC
FEV/FVC at other time points and as summary measures over time using mixed effects modeling;
Time frame: Through study completion, an average of 12 months
Exacerbations
Number and severity of exacerbations
Time frame: Through study completion, an average of 12 months
Respiratory QoL at multiple time points
Measured using questionnaires
Time frame: Through study completion, an average of 12 months
Respiratory symptoms
Respiratory symptoms at multiple time points
Time frame: Through study completion, an average of 12 months
Whole blood total glutathione
Whole blood total glutathione at multiple time points
Time frame: Through study completion, an average of 12 months
Mtb sputum culture
Microbiological test that detects viable Mycobacterium tuberculosis in sputum samples
Time frame: Month 2, 3 and 6
Change in MGIT (Mycobacterial Growth Indicator Tube) time to positivity (TTP): assessed over time through repeated measurements
To reflect treatment response
Time frame: Through study completion, an average of 12 months
Treatment failure
TB Treatment failure during the study period.
Time frame: Through study completion, an average of 12 months
TB recurrence
TB recurrence during the study period
Time frame: Through study completion, an average of 12 months
Number and severity of hepatic safety events
Safety measures monitored throughout the study period.
Time frame: Through study completion, an average of 12 months
Number and severity of adverse events (SAEs)
Safety measures monitored throughout the study period.
Time frame: Through study completion, an average of 12 months
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