- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03702738
Adjunctive NAC in Adult Patients With Pulmonary Tuberculosis (NAC-TB)
January 18, 2021 updated by: The Aurum Institute NPC
A Prospective Randomized Controlled Trial of Adjunctive N-acetylcysteine (NAC) in Adult Patients With Pulmonary Tuberculosis: a Sub-study of TB Sequel
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
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Anticipated)
110
Phase
- Phase 2
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
- Name: Robert Wallis
- Phone Number: +27 (0) 10 590 1322
- Email: rwallis@auruminstitute.org
Study Locations
-
-
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Mbeya, Tanzania
- Recruiting
- NIMR-Mbeya Medical Research Centre
-
-
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
16 years to 63 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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
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: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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
|
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.
Other Names:
|
No Intervention: No NAC
Patients will be randomized to receive 6 months standard TB treatment alone
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Median time to stable sputum culture conversion using liquid medium
Time Frame: 6 months
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
1-28 days
|
GSH concentrations and the ratio of GSH to GSSG (oxidized glutathione) measured at discrete time points during treatment
Time Frame: 6 months
|
6 months
|
Whole blood bactericidal activity (WBA) prior and at intervals post dosing
Time Frame: 24 hours
|
24 hours
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Robert Wallis, Chief Scientific Officer
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)
March 1, 2019
Primary Completion (Anticipated)
December 31, 2021
Study Completion (Anticipated)
December 31, 2021
Study Registration Dates
First Submitted
October 4, 2018
First Submitted That Met QC Criteria
October 9, 2018
First Posted (Actual)
October 11, 2018
Study Record Updates
Last Update Posted (Actual)
January 22, 2021
Last Update Submitted That Met QC Criteria
January 18, 2021
Last Verified
January 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Lung Diseases
- Bacterial Infections
- Bacterial Infections and Mycoses
- Gram-Positive Bacterial Infections
- Actinomycetales Infections
- Mycobacterium Infections
- Tuberculosis
- Tuberculosis, Pulmonary
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Protective Agents
- Respiratory System Agents
- Antioxidants
- Antidotes
- Free Radical Scavengers
- Expectorants
- Acetylcysteine
- N-monoacetylcystine
Other Study ID Numbers
- AUR1-1-219
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
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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