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Adjunctive NAC in Adult Patients With Pulmonary Tuberculosis (NAC-TB)

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ClinicalTrials.gov Identifier: NCT03702738
Recruitment Status : Not yet recruiting
First Posted : October 11, 2018
Last Update Posted : January 10, 2019
Sponsor:
Collaborator:
National Institute for Medical Research, Tanzania
Information provided by (Responsible Party):
The Aurum Institute NPC

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

Condition or disease Intervention/treatment Phase
Tuberculosis, Pulmonary Drug: N-acetyl cysteine Phase 2

Detailed Description:
This is a randomized controlled, 2-arm, parallel group substudy of the TB-SEQUEL cohort study. It will enrol drug sensitive TB patients with moderately advanced or far advanced pulmonary disease by chest X-ray. Patients providing informed consent will undergo screening evaluations to establish eligibility. Patients meeting all the inclusion and none of the exclusion criteria will be randomized to receive standard TB treatment (2HRZE/4HR) plus NAC 1200 mg BID for months 1-4, or standard treatment alone. During the treatment period patients will undergo safety, efficacy, and biomarker assessments at specified time points. After a final evaluation at 6 months, patients will continue follow-up as a part of the main TB-SEQUEL cohort study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective Randomized Controlled Trial of Adjunctive N-acetylcysteine (NAC) in Adult Patients With Pulmonary Tuberculosis: a Sub-study of TB Sequel
Estimated Study Start Date : March 1, 2019
Estimated Primary Completion Date : October 30, 2020
Estimated Study Completion Date : October 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Arm Intervention/treatment
Experimental: NAC
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
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.

No Intervention: No NAC
Patients will be randomized to receive 6 months standard TB treatment alone



Primary Outcome Measures :
  1. Median time to stable sputum culture conversion using liquid medium [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Change from baseline in mean concentration of reduced glutathione (GSH) in blood cells, expressed as the AUC during days 1-28 [ Time Frame: 1-28 days ]
  2. GSH concentrations and the ratio of GSH to GSSG (oxidized glutathione) measured at discrete time points during treatment [ Time Frame: 6 months ]
  3. Whole blood bactericidal activity (WBA) prior and at intervals post dosing [ Time Frame: 24 hours ]


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

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
  2. Current or imminent (within 24 hr) treatment for malaria.
  3. Pregnancy
  4. 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.
  5. TB meningitis or other forms of severe tuberculosis with high risk of a poor outcome as judged by the investigator.
  6. History of allergy or hypersensitivity to any of the trial therapies or related substances, including known allergy or suspected hypersensitivity to rifampin.
  7. Having participated in other clinical trials with investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational trial.
  8. Prior TB treatment in the preceding 6 months.
  9. Angina pectoris requiring treatment with nitroglycerin or other nitrates
  10. Cardiac arrhythmia requiring medication, or any clinically significant ECG abnormality, in the opinion of the investigator
  11. 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.
  12. Use of systemic corticosteroids within the past 28 days.
  13. Patients requiring treatment with medications not compatible with rifampin, such as HIV-1 protease inhibitors
  14. 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

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Responsible Party: The Aurum Institute NPC
ClinicalTrials.gov Identifier: NCT03702738     History of Changes
Other Study ID Numbers: AUR1-1-219
First Posted: October 11, 2018    Key Record Dates
Last Update Posted: January 10, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by The Aurum Institute NPC:
Host-directed therapy
N-acetylcysteine
Glutathione

Additional relevant MeSH terms:
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Acetylcysteine
N-monoacetylcystine
Tuberculosis
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Antiviral Agents
Anti-Infective Agents
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes