Skip to content

Research at St Andrews

Accuracy and consequences of using trial-of-antibiotics for TB diagnosis (ACT-TB study): protocol for a randomised controlled clinical trial

Research output: Contribution to journalArticle

Author(s)

Titus Henry Divala, Katherine L. Fielding, Derek J. Sloan, Neil French, Marriott Nliwasa, Peter MacPherson, Chikondi Charity Kandulu, Lingstone Chiume, Sanderson Chilanga, Masiye John Ndaferankhande, Elizabeth L. Corbett

School/Research organisations

Abstract

Introduction Over 40% of global tuberculosis case notifications are diagnosed clinically without mycobacteriological confirmation. Standard diagnostic algorithms include ‘trial-of-antibiotics’—empirical antibiotic treatment given to mycobacteriology-negative individuals to treat infectious causes of symptoms other than tuberculosis, as a ‘rule-out’ diagnostic test for tuberculosis. Potentially 26.5 million such antibiotic courses/year are prescribed globally for the 5.3 million/year mycobacteriology-negative patients, making trial-of-antibiotics the most common tuberculosis diagnostic, and a global-scale risk for antimicrobial resistance (AMR). Our systematic review found no randomised controlled trial (RCT) to support use of trial-of-antibiotic. The RCT aims to determine the diagnostic and clinical value and AMR consequences of trial-of-antibiotics.

Methods and analysis A three-arm, open-label, RCT randomising (1:1:1) Malawian adults (≥18 years) seeking primary care for cough into: (a) azithromycin 500 mg one time per day for 3 days or (b) amoxicillin 1 g three times per day for 5 days or (c) standard-of-care (no immediate antibiotic). We will perform mycobacteriology tests (microscopy, Xpert MTB/RIF (Mycobacterium tuberculosis/rifampicin) and Mycobacterium tuberculosis culture) at baseline. We will use audiocomputer-assisted self-interview to assess clinical improvement at day 8. First primary outcome will be proportion of patients reporting day 8 improvement out of those with negative mycobacteriology (specificity). Second primary outcome will be day 29 incidence of a composite endpoint of either death or hospitalisation or missed tuberculosis diagnosis. To determine AMR impact we compare proportion of resistant nasopharyngeal Streptococcus pneumoniae isolates on day 29. 400 mycobacteriology-negative participants/arm will be required to detect a ≥10% absolute difference in diagnostic specificity with 80% power. We will estimate measures of effect by comparing outcomes in antibiotic arms (combined and individually) to standard-of-care.

Ethics and dissemination The study has been reviewed and approved by Malawi College of Medicine Research and Ethics Committee, London School of Hygiene & Tropical Medicine (LSHTM) Research Ethics Committee and Regional Committee for Health and Research Ethics – Norway, and Malawi Pharmacy, Medicines and Poisons Board. We will present abstracts at relevant conferences, and prepare a manuscript for publication in a peer-reviewed journal.

Close

Details

Original languageEnglish
Article numbere033999
Number of pages10
JournalBMJ Open
Volume10
Issue number3
Early online date25 Mar 2020
DOIs
Publication statusPublished - Mar 2020

    Research areas

  • Antibiotics, Antimicrobial resistance, Diagnostic performance, TB, Trial-of-antibiotics, Tuberculosis

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Utility of broad-spectrum antibiotics for diagnosing pulmonary tuberculosis in adults: a systematic review and meta-analysis

    Divala, T. H., Fielding, K. L., Kandulu, C., Nliwasa, M., Gupta-Wright, A., Sloan, D. J. & Corbett, E. L., 18 May 2020, In : Lancet Infectious Diseases. Online First, 10 p.

    Research output: Contribution to journalArticle

  2. A tuberculosis molecular bacterial load assay (TB-MBLA)

    Sabiiti, W., Mtafya, B. A., Alferes De Lima, D., Dombay, E., Baron, V. O., Azam, K., Orascova, K., Sloan, D. J. & Gillespie, S. H., 30 Apr 2020, In : Journal of Visualized Experiments. 158, 10 p., e60460.

    Research output: Contribution to journalArticle

  3. Tuberculosis bacillary load, an early marker of disease severity and treatment response: the utility of tuberculosis Molecular Bacterial Load Assay

    Sabiiti, W., Azam, K., Farmer, E., Kuchaka, D., Mtafya, B., Bowness, R., Oravcova, K., Honeyborne, I., Evangelopoulos, D., McHugh, T. D., Khosa, C., Rachow, A., Heinrich, N., Kampira, E., Davies, G., Bhatt, N., Ntinginya, E. N., Viegas, S., Jani, I., Kamdolozi, M. & 8 others, Mdolo, A., Khonga, M., Boeree, M. J., Phillips, P. PJ., Sloan, D. J., Hoelscher, M., Kibiki, G. S. & Gillespie, S. H., 30 Apr 2020, In : Thorax. Online First, 3 p.

    Research output: Contribution to journalArticle

  4. Pharmacokinetics, SAfety/tolerability, and EFficacy of high-dose RIFampicin in tuberculosis-HIV co-infected patients on efavirenz- or dolutegravir-based antiretroviral therapy: study protocol for an open-label phase II clinical trial (SAEFRIF)

    Nabisere, R., Musaazi, J., Denti, P., Aber, F., Lamorde, M., Dooley, K. E., Aarnoutse, R., Sloan, D. J. & Sekaggya-Wiltshire, C., 13 Feb 2020, In : Trials. 21, 9 p., 181.

    Research output: Contribution to journalArticle

  5. PrimeStore MTM and OMNIgene sputum for the preservation of sputum for Xpert MTB/RIF testing in Nigeria

    Bimba, J. S., Lawson, L., Kontogianni, K., Edwards, T., Ekpenyong, B. E., Dodd, J., Adams, E. R., Sloan, D. J., Cresswell, J., Dominguez, J. & Cuevas, L. E., 4 Dec 2019, In : Journal of Clinical Medicine. 8, 12, 9 p., 2146.

    Research output: Contribution to journalArticle

Related by journal

  1. A cohort study of high maternal Body Mass Index and the risk of adverse pregnancy and delivery outcomes in Scotland

    Doi, L., Williams, A. J., Marryat, L. & Frank, J., 20 Feb 2020, In : BMJ Open. 10, 2, 9 p., e026168.

    Research output: Contribution to journalArticle

ID: 267565322

Top