Adjunctive NAC in Adult Patients With Pulmonary Tuberculosis

NCT03702738 | Completed Phase 2 DMC

• 1 other identifier: AUR1-1-219
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

To determine if adjunctive N-acetylcysteine 1200 mg twice a day (BID) accelerates sputum culture conversion and normalization of cellular glutathione in tuberculosis (TB), and to assess its potential effects on lung and immune function

Conditions

Tuberculosis, Pulmonary

Keywords

Host-directed therapy; N-acetylcysteine; Glutathione

Outcome Measures

Primary Outcomes (1)

• Median time to stable sputum culture conversion using liquid medium

  6 months

Secondary Outcomes (3)

• Change from baseline in mean concentration of reduced glutathione (GSH) in blood cells, expressed as the AUC during days 1-28

  1-28 days

• GSH concentrations and the ratio of GSH to GSSG (oxidized glutathione) measured at discrete time points during treatment

  6 months

• Whole blood bactericidal activity (WBA) prior and at intervals post dosing

  24 hours

Study Arms (2)

NAC

EXPERIMENTAL

Patients will be randomized to receive standard TB treatment with N-acetylcysteine 1200 mg BID x 4 months, followed by 2 months of standard TB treatment alone

Drug: N-acetyl cysteine

No NAC

NO INTERVENTION

Patients will be randomized to receive 6 months standard TB treatment alone

Interventions

N-acetyl cysteine DRUG

NAC is listed by WHO as an essential medicine for its use in paracetamol (acetaminophen) poisoning, in which it protects against fatal liver injury. It also reduces the viscosity of sputum, thereby serving as an expectorant.

Also known as: NAC

NAC

Eligibility Criteria

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

You may qualify if:

• Aged 18 to 65 years, male or female
• Willing and able to provide signed written consent or witnessed oral consent in the case of illiteracy, prior to undertaking any trial related procedures.
• Body weight (in light clothing without shoes) between 40 and 90 kg.
• First episode of pulmonary tuberculosis
• Positive sputum AFB smear with subsequent culture confirmation OR positive Xpert TB/RIF with Ct ≤27.1 \[3\].
• RIF susceptibility diagnosed by Xpert TB/RIF OR Hain test
• Chest radiograph meeting criteria for moderate or far advanced pulmonary tuberculosis \[4\]
• If sexually active, willing to use an effective contraceptive method for the duration of tuberculosis treatment
• HIV-1 seronegative, or if HIV-1 seropositive, CD4 T cell count \>220/ul

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
• Current or imminent (within 24 hr) treatment for malaria.
• Pregnancy
• 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.
• Prior 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 history of unstable Diabetes Mellitus which required hospitalization for hyper- or hypo-glycaemia within the past year prior to start of screening.
• Use of systemic corticosteroids within the past 28 days.
• Patients requiring treatment with medications not compatible with rifampin, such as HIV-1 protease inhibitors
• Subjects with any of the following abnormal laboratory values:
• creatinine \>2 mg/dL

Sponsors & Collaborators

• The Aurum Institute NPC: lead
• National Institute for Medical Research, Tanzania: collaborator

Study Sites (1)

NIMR-Mbeya Medical Research Centre

Mbeya, Tanzania

Location

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 DERIVED

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Robert Wallis

  Chief Scientific Officer

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2018
• First Posted: October 11, 2018
• Study Start: March 1, 2019
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

TA (1)