Tuberculosis (TB)NAC-PTLDNCT06909799
A Confirmatory Trial of Adjunctive NAC to Prevent Post Tuberculosis Lung Disease
A study testing N-Acetyl Cysteine (NAC) and Standard TB treatment in people with Tuberculosis (TB), run by The Aurum Institute NPC at 1 site in The Gambia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Tuberculosis (TB)
- What is being tested?
- N-Acetyl Cysteine (NAC) and Standard TB treatment
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 242 participants
- Where
- 1 siteThe Gambia
- Study dates
- 28 Apr 2025to 31 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 21Show fewer
- 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
- platelets <100x109 cells/L
- serum potassium <3.5
- aspartate aminotransferase (AST) ≥2.0 x ULN
- alkaline phosphatase (AP) >5.0 x ULN
- total bilirubin >1.5 mg/dL
- positive HBsAg
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
The Gambia1 site, 1 recruiting
- Recruiting
MRC Unit The Gambia at LSHTM
Fajara, The Gambia
Bintou Njai, MBBS, +220 761 26 24, bnjai@mrc.gm
About this study
Official title: 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.
Read the 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.
- Conditions
- Tuberculosis (TB)
- Being tested
- N-Acetyl Cysteine (NAC), Standard TB treatment
- Keywords
- NAC, N-acetylcysteine, HDT, Host directed therapy, PTLD, Post TB lung disease
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
Standard TB treatmentDrug
Standard TB treatment will be provided as fixed dose combination tablets.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Standard TB treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
FEV1% of predicted at month 12
Measured by spirometry
Measured: month 12
Secondary outcomes (13)
FEV1%
FEV1%, at other time points and as summary measures over time
Measured: Through study completion, an average of 12 months
FVC%
FVC%, at other time points and as summary measures over time using mixed effects modeling;
Measured: 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;
Measured: Through study completion, an average of 12 months
Exacerbations
Number and severity of exacerbations
Measured: Through study completion, an average of 12 months
Respiratory QoL at multiple time points
Measured using questionnaires
Measured: Through study completion, an average of 12 months
Respiratory symptoms
Respiratory symptoms at multiple time points
Measured: Through study completion, an average of 12 months
Whole blood total glutathione
Whole blood total glutathione at multiple time points
Measured: Through study completion, an average of 12 months
Mtb sputum culture
Microbiological test that detects viable Mycobacterium tuberculosis in sputum samples
Measured: 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
Measured: Through study completion, an average of 12 months
Treatment failure
TB Treatment failure during the study period.
Measured: Through study completion, an average of 12 months
TB recurrence
TB recurrence during the study period
Measured: Through study completion, an average of 12 months
Number and severity of hepatic safety events
Safety measures monitored throughout the study period.
Measured: Through study completion, an average of 12 months
Number and severity of adverse events (SAEs)
Safety measures monitored throughout the study period.
Measured: Through study completion, an average of 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2025
- Study start28 Apr 2025
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Tuberculosis (TB)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 242 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Aurum Institute NPC
- Sponsor type
- University, hospital or other
- Collaborators
- Ludwig-Maximilians - University of Munich, Research Center Borstel
- Responsible party
- Sponsor
- Investigators
- Robert Wallis - Professor, Principal investigator, Aurum InstituteAndrea Rachow, MD, Principal investigator, LMU
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06909799
- Sponsor's protocol ID
- AUR1-1-420
- Acronym
- NAC-PTLD
- Status last verified
- Apr 2025
- First submitted
- 8 Nov 2024
- Last updated
- 30 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized IPD will be shared
Publications
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.
PubMed 39189858
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Confirmatory Trial of Adjunctive N-acetylcysteine to Prevent Post Tuberculosis Lung Disease (NAC-PTLD) - A TB SEQUEL II Substudy
- ClinicalTrials.gov ID
- NCT06909799
- Acronym / sponsor ID
- NAC-PTLD / AUR1-1-420
- Conditions
- Tuberculosis (TB)
- Keywords
- NAC, N-acetylcysteine, HDT, Host directed therapy, PTLD, Post TB lung disease
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 242 participants (estimated)
- Lead sponsor
- The Aurum Institute NPCUniversity, hospital or other
- Collaborators
- Ludwig-Maximilians - University of Munich, Research Center Borstel
- Study start
- 28 Apr 2025 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 4 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| N-Acetylcysteine (NAC) 1800mg orally twice a day plus TB treatment during months 1-6. | Experimental | Drug: N-Acetyl Cysteine (NAC), Drug: Standard TB treatmentN-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 | Active comparator | Drug: Standard TB treatmentStandard TB treatment for 6 months followed by 6 months of observation. TB treatment will be provided as fixed dose combination tablets. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | N-Acetylcysteine (NAC) 1800mg orally twice a day plus TB treatment during months 1-6. |
| Standard TB treatmentStandard TB treatment will be provided as fixed dose combination tablets. | Drug | N-Acetylcysteine (NAC) 1800mg orally twice a day plus TB treatment during months 1-6., Standard TB treatment during months 1-6 |
Primary outcome
FEV1% of predicted at month 12
Time frame: month 12
Measured by spirometry
13 secondary outcomes
FEV1%
Time frame: Through study completion, an average of 12 months
FVC%
Time frame: Through study completion, an average of 12 months
FEV/FVC
Time frame: Through study completion, an average of 12 months
Exacerbations
Time frame: Through study completion, an average of 12 months
Respiratory QoL at multiple time points
Time frame: Through study completion, an average of 12 months
Respiratory symptoms
Time frame: Through study completion, an average of 12 months
Whole blood total glutathione
Time frame: Through study completion, an average of 12 months
Mtb sputum culture
Time frame: 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
Treatment failure
Time frame: Through study completion, an average of 12 months
TB recurrence
Time frame: 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
Number and severity of adverse events (SAEs)
Time frame: Through study completion, an average of 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2025.
- Background: PubMed 39189858Wallis 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.
- TB Sequel websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Anonymized IPD will be shared
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Robert Wallis - Professor principal investigator
Aurum Institute
Andrea Rachow, MD principal investigator
LMU
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing N-Acetyl Cysteine (NAC) and Standard TB treatment in people with Tuberculosis (TB), run by The Aurum Institute NPC at 1 site in The Gambia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in The Gambia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Fadzai E Munedzimwe, MPH (+27(0)0105901300, FMunedzimwe@auruminstitute.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
FEV1% of predicted at month 12 (time frame: month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06909799, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2025.