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

NCT06909799 | Recruiting DMC

• 1 other identifier: AUR1-1-420
• Study Type: interventional
• Target: 242
• Locations: 1 country
• Sites: 1

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.

Conditions

Tuberculosis (TB)

Keywords

NAC; N-acetylcysteine; HDT; Host directed therapy; PTLD; Post TB lung disease

Outcome Measures

Primary Outcomes (1)

• FEV1% of predicted at month 12

  Measured by spirometry

  month 12

Secondary Outcomes (13)

• FEV1%

  Through study completion, an average of 12 months

• FVC%

  Through study completion, an average of 12 months

• FEV/FVC

  Through study completion, an average of 12 months

• Exacerbations

  Through study completion, an average of 12 months

• Respiratory QoL at multiple time points

  Through study completion, an average of 12 months

Study Arms (2)

N-Acetylcysteine (NAC) 1800mg orally twice a day plus TB treatment during months 1-6.

EXPERIMENTAL

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.

Drug: N-Acetyl Cysteine (NAC); Drug: Standard TB treatment

Standard TB treatment during months 1-6

ACTIVE COMPARATOR

Standard TB treatment for 6 months followed by 6 months of observation. TB treatment will be provided as fixed dose combination tablets.

Drug: Standard TB treatment

Interventions

N-Acetyl Cysteine (NAC) DRUG

NAC will be provided as 600 mg capsules from NOW Healthgroup. Standard TB treatment will be provided as fixed dose combination tablets.

N-Acetylcysteine (NAC) 1800mg orally twice a day plus TB treatment during months 1-6.

Standard TB treatment DRUG

Standard TB treatment will be provided as fixed dose combination tablets.

N-Acetylcysteine (NAC) 1800mg orally twice a day plus TB treatment during months 1-6.; Standard TB treatment during months 1-6

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Persons aged 18 to 65 years
• 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.
• Body weight (in light clothing without shoes) between 30 and 90 kg.
• Xpert TB/RIF OR Ultra showing RIF-S-MTB, with subsequent confirmation of MTB by culture.
• Chest radiograph meeting criteria for moderate or far advanced pulmonary tuberculosis 1
• FEV1 ≤65% of predicted adjusted for age, height, sex, and race
• If female, of child-bearing potential and sexually active, willing to use a contraceptive method for the duration of study participation
• 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

You may not qualify if:

• 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
• Pregnancy or breast-feeding
• 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.
• TB meningitis or other forms of severe tuberculosis with high risk of a poor outcome as judged by the investigator.
• History of allergy or hypersensitivity to any of the trial therapies or related substances, including known allergy or suspected hypersensitivity to rifampin.
• Having participated in other clinical trials with investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational trial.
• No more than 5 days treatment for the current TB episode, and no other TB treatment in the preceding 6 months
• Angina pectoris requiring treatment with nitroglycerin or other nitrates
• Cardiac arrhythmia requiring medication, or any clinically significant ECG abnormality, in the opinion of the investigator
• 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.
• 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.
• Patients requiring treatment with medications not compatible with rifampin, such as HIV protease inhibitors
• Subjects with any of the following abnormal laboratory values:
• creatinine \>2 mg/dL
• haemoglobin \<8 g/dL

Sponsors & Collaborators

• The Aurum Institute NPC: lead
• Ludwig-Maximilians - University of Munich: collaborator
• Research Center Borstel: collaborator

Study Sites (1)

MRC Unit The Gambia at LSHTM

Fajara, The Gambia, The Gambia

RECRUITING

Related Publications (1)

• Wallis RS, Sabi I, Lalashowi J, Bakuli A, Mapamba D, Olomi W, Siyame E, Ngaraguza B, Chimbe O, Charalambous S, Rachow A, Ivanova O, Zurba L, Myombe B, Kunambi R, Hoelscher M, Ntinginya N, Churchyard G. Adjunctive N-Acetylcysteine and Lung Function in Pulmonary Tuberculosis. NEJM Evid. 2024 Sep;3(9):EVIDoa2300332. doi: 10.1056/EVIDoa2300332. Epub 2024 Aug 27.

  PMID: 39189858 BACKGROUND

Related Links

• TB Sequel website

MeSH Terms

Conditions

Tuberculosis

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Robert Wallis - Professor

  Aurum Institute

  PRINCIPAL INVESTIGATOR

• Andrea Rachow, MD

  LMU

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fadzai E Munedzimwe, MPH

CONTACT

+27(0)0105901300; FMunedzimwe@auruminstitute.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: NAC dosing will be 1800mg PO BID during months 1-6, or control, depending on study arm. All participants will also receive standard TB treatment.

Study Record Dates

• First Submitted: November 8, 2024
• First Posted: April 4, 2025
• Study Start: April 28, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 30, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available after the publication of the primary trial report. The end date has not yet been determined.
• Access Criteria: Access will be available through the NIH TB Portals system.

Locations

TH (1)