A Confirmatory Trial of Adjunctive NAC to Prevent Post Tuberculosis Lung Disease

Not Applicable

Recruiting

• Conditions: Tuberculosis (TB)
• Interventions: Drug: N-Acetyl Cysteine (NAC); Drug: Standard TB treatment

• Registration Number: NCT06909799
• Lead Sponsor: The Aurum Institute NPC

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2024-11-08
• Study First Submitted QC: 2025-03-27
• Status Verified: 2025-04
• Study First Posted: 2025-04-04
• Study Start: 2025-04-28
• Last Update Submitted: 2025-04-28
• Last Update Posted: 2025-04-30
• Primary Completion: 2027-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 242

Inclusion Criteria

1. Persons aged 18 to 65 years
2. Willing and able to provide signed written consent, or witnessed oral con-sent with thumbprint in the case of illiteracy, prior to undertaking any trial-related procedures.
3. Body weight (in light clothing without shoes) between 30 and 90 kg.
4. Xpert TB/RIF OR Ultra showing RIF-S-MTB, with subsequent confirmation of MTB by culture.
5. Chest radiograph meeting criteria for moderate or far advanced pulmonary tuberculosis 1
6. FEV1 ≤65% of predicted adjusted for age, height, sex, and race
7. If female, of child-bearing potential and sexually active, willing to use a contraceptive method for the duration of study participation
8. HIV-1/2 seronegative, or if seropositive: CD4 T cell count ≥100/mcL and either currently receiving ART or willing to start ART during study participation

Exclusion Criteria

1. Any condition for which participation in the trial, as judged by the investigator, could compromise the well-being of the subject or prevent, limit or confound protocol specified assessments, such as pneumothorax or clinically significant pleural effusion

2. Pregnancy or breast-feeding

3. Is critically ill, and in the judgment of the investigator has a diagnosis likely to result in death during the trial or the follow-up period.

4. TB meningitis or other forms of severe tuberculosis with high risk of a poor outcome as judged by the investigator.

5. History of allergy or hypersensitivity to any of the trial therapies or related substances, including known allergy or suspected hypersensitivity to rifampin.

6. Having participated in other clinical trials with investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational trial.

7. No more than 5 days treatment for the current TB episode, and no other TB treatment in the preceding 6 months

8. Angina pectoris requiring treatment with nitroglycerin or other nitrates

9. Cardiac arrhythmia requiring medication, or any clinically significant ECG abnormality, in the opinion of the investigator

10. Random blood glucose >140 mg/dL (or >7.8 mmol/L), or history of unstable Diabetes Mellitus which required hospitalization for hyper- or hypoglycaemia within the past year prior to start of screening.

11. Use of systemic corticosteroids within the past 28 days, or a likely to require corticosteroids for management of another medical condition during the period of study participation.

12. Patients requiring treatment with medications not compatible with rifampin, such as HIV protease inhibitors

13. Subjects with any of the following abnormal laboratory values:

    1. creatinine >2 mg/dL
    2. haemoglobin <8 g/dL
    3. platelets <100x109 cells/L
    4. serum potassium <3.5
    5. aspartate aminotransferase (AST) ≥2.0 x ULN
    6. alkaline phosphatase (AP) >5.0 x ULN
    7. total bilirubin >1.5 mg/dL
    8. positive HBsAg

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
N-Acetylcysteine (NAC) 1800mg orally twice a day plus TB treatment during months 1-6.	N-Acetyl Cysteine (NAC)	N-Acetylcysteine (NAC) dosing will be 1800mg orally twice a day during months 1-6 plus standard TB treatment. This will be followed by 6 months follow up.
N-Acetylcysteine (NAC) 1800mg orally twice a day plus TB treatment during months 1-6.	Standard TB treatment	N-Acetylcysteine (NAC) dosing will be 1800mg orally twice a day during months 1-6 plus standard TB treatment. This will be followed by 6 months follow up.
Standard TB treatment during months 1-6	Standard TB treatment	Standard TB treatment for 6 months followed by 6 months of observation. TB treatment will be provided as fixed dose combination tablets.

Primary Outcome Measures

Name	Time	Method
FEV1% of predicted at month 12	month 12	Measured by spirometry

Secondary Outcome Measures

Name	Time	Method
Change in MGIT (Mycobacterial Growth Indicator Tube) time to positivity (TTP): assessed over time through repeated measurements	Through study completion, an average of 12 months	To reflect treatment response
FEV1%	Through study completion, an average of 12 months	FEV1%, at other time points and as summary measures over time
FVC%	Through study completion, an average of 12 months	FVC%, at other time points and as summary measures over time using mixed effects modeling;
FEV/FVC	Through study completion, an average of 12 months	FEV/FVC at other time points and as summary measures over time using mixed effects modeling;
Exacerbations	Through study completion, an average of 12 months	Number and severity of exacerbations
Respiratory QoL at multiple time points	Through study completion, an average of 12 months	Measured using questionnaires
Respiratory symptoms	Through study completion, an average of 12 months	Respiratory symptoms at multiple time points
Whole blood total glutathione	Through study completion, an average of 12 months	Whole blood total glutathione at multiple time points
Mtb sputum culture	Month 2, 3 and 6	Microbiological test that detects viable Mycobacterium tuberculosis in sputum samples
Treatment failure	Through study completion, an average of 12 months	TB Treatment failure during the study period.
TB recurrence	Through study completion, an average of 12 months	TB recurrence during the study period
Number and severity of hepatic safety events	Through study completion, an average of 12 months	Safety measures monitored throughout the study period.
Number and severity of adverse events (SAEs)	Through study completion, an average of 12 months	Safety measures monitored throughout the study period.

Trial Locations

Locations (1)

MRC Unit The Gambia at LSHTM; 🇬🇲 Fajara, The Gambia, Gambia