Background New drug classes and regimens have shortened the treatment duration for drug-resistant tuberculosis, but adverse events (AEs) and organ toxicity remain unacceptably common. N-acetylcysteine (NAC) has demonstrated potential in reducing kidney and liver toxicity in other clinical settings, but efficacy in drug-resistant tuberculosis treatment has not been rigorously evaluated.

Method A randomized controlled trial (PACTR202007736854169) was conducted at Kibong’oto Infectious Disease Hospital in Tanzania to assess the efficacy of NAC in reducing AEs in patients undergoing rifampin-resistant pulmonary tuberculosis treatment. Participants received an all-oral standardized rifampin-resistant regimen alone, with NAC 900 mg daily, or NAC 900 mg twice daily for 6 months. AEs, severe AEs, and renal and liver toxicity were monitored monthly and classified according to the Risk, Injury, Failure, Loss, and End-stage kidney disease criteria and National Cancer Institute Common Terminology Criteria for Adverse Events. Incident ratios and Kaplan-Meier curves were employed to compare group event occurrences.

Results 66 patients (mean age 47±12 years; 80% male) were randomized into three groups of 22. One hundred and fifty-eight AEs were recorded: 52 (33%) in the standard treatment group, 55 (35%) in the NAC 900 mg daily group, and 51 (32%) in the NAC 900 mg twice daily group (p>0.99). Severe AEs were observed in 4 patients in the standard group, 2 in the NAC 900 mg daily group, and 3 in the NAC 900 mg twice daily group. Renal toxicity was more prevalent in the standard treatment group (45% vs. 23%; p=0.058), with a shorter onset of time to toxicity (χ2 = 3.199; p=0.074). Liver injury events were rare across all groups.

Conclusion Among Tanzanian adults receiving rifampin-resistant tuberculosis treatment, NAC did not significantly reduce overall AEs but demonstrated important trends in reducing renal toxicity.

The authors have declared no competing interest.

PACTR202007736854169

This Study was funded by European & Developing Countries Clinical Trial Partnerships

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethic committee IRB of Tanzanian National Institute of Medical Research gave approval for this work

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Kibog’oto Infectious Diseases Hospital:

Happiness Mvungi; happinesscornelgmail.com

Kassim Salim; kassimsalim206gmail.com

Oscar Kasawaga; oscarlkaswagagmail.com

Peter Mbelele; mbelelepeteryahoo.com

Alphonce Liyoyo; Liyoyo2020gmail.com

Athumani Ngoma; Athmatzan3gmail.com

Kilimanjaro Christian Medical College:

Happiness Mvungi; happinesscornelgmail.com

Stellah G Mpagama MD, MSC, PhD sempagamayahoo.com

Hadija Semuva; H.semvuakcri.ac.tz

Division Of Infectious Diseases and International Health University of Virginia Scott Heysell; SKH8Ruvahealth.org

All data produced in the present study are available upon reasonable request to the authors All data produced in the present work are contained in the manuscript All data produced are available online at