A Confirmatory Trial of Adjunctive NAC to Prevent Post Tuberculosis Lung Disease (NAC-PTLD)

April 28, 2025 updated by: The Aurum Institute NPC

A Confirmatory Trial of Adjunctive N-acetylcysteine to Prevent Post Tuberculosis Lung Disease (NAC-PTLD) - A TB SEQUEL II Substudy

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 Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

242

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Gambia
    • The Gambia
      • Fajara, The Gambia, Gambia
        • Recruiting
        • MRC Unit The Gambia at LSHTM
        • Contact:
          • Bintou Njai, MBBS
          • Phone Number: +220 761 26 24
          • Email: bnjai@mrc.gm

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: N-Acetylcysteine (NAC) 1800mg orally twice a day plus TB treatment during months 1-6.
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)
NAC will be provided as 600 mg capsules from NOW Healthgroup. Standard TB treatment will be provided as fixed dose combination tablets.
Drug: Standard TB treatment
Standard TB treatment will be provided as fixed dose combination tablets.
Active Comparator: Standard TB treatment during months 1-6
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
Standard TB treatment will be provided as fixed dose combination tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
FEV1% of predicted at month 12
Time Frame: month 12
Measured by spirometry
month 12

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Aurum Institute NPC

Collaborators

Ludwig-Maximilians - University of Munich
Research Center Borstel

Investigators

  • Principal Investigator: Robert Wallis - Professor, Aurum Institute
  • Principal Investigator: Andrea Rachow, MD, LMU

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 28, 2025

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

November 8, 2024

First Submitted That Met QC Criteria

March 27, 2025

First Posted (Actual)

April 4, 2025

Study Record Updates

Last Update Posted (Actual)

April 30, 2025

Last Update Submitted That Met QC Criteria

April 28, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AUR1-1-420

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Anonymized IPD will be shared

IPD Sharing Time Frame

IPD will be made available after the publication of the primary trial report. The end date has not yet been determined.

IPD Sharing Access Criteria

Access will be available through the NIH TB Portals system.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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