Skip to content

Research at St Andrews

A partially randomised trial of pretomanid, moxifloxacin and pyrazinamide for pulmonary TB

Research output: Contribution to journalArticlepeer-review

DOI

Open Access permissions

Open

Author(s)

C. D. Tweed, G. H. Wills, A. M. Crook, E. Amukoye, V. Balanag, A. Y.L. Ban, A. L.C. Bateson, M. C. Betteridge, W. Brumskine, J. Caoili, R. E. Chaisson, M. Cevik, F. Conradie, R. Dawson, A. del Parigi, A. Diacon, D. E. Everitt, S.M. Fabiane, R. Hunt, A. I. Ismail & 19 more U. Lalloo, L. Lombard, C. Louw, M. Malahleha, T. D. McHugh, C. M. Mendel, F. Mhimbira, R. N. Moodliar, V. Nduba, A. J. Nunn, I. Sabi, M. A. Sebe, R. A. P. Selepe, S. Staples, S. Swindells, C. H. van Niekerk, E. Variava, M. Spigelman, S. H. Gillespie

School/Research organisations

Abstract

BACKGROUND: Treatment for TB is lengthy and toxic, and new regimens are needed.
METHODS: Participants with pulmonary drug-susceptible TB (DS-TB) were randomised to receive: 200 mg pretomanid (Pa, PMD) daily, 400 mg moxifloxacin (M) and 1500 mg pyrazinamide (Z) for 6 months (6Pa200MZ) or 4 months (4Pa200MZ); 100 mg pretomanid daily for 4 months in the same combination (4Pa100MZ); or standard DS-TB treatment for 6 months. The primary outcome was treatment failure or relapse at 12 months post-randomisation. The non-inferiority margin for between-group differences was 12.0%. Recruitment was paused following three deaths and not resumed.
RESULTS: Respectively 4/47 (8.5%), 11/57 (19.3%), 14/52 (26.9%) and 1/53 (1.9%) DS-TB outcomes were unfavourable in patients on 6Pa200MZ, 4Pa200MZ, 4Pa100MZ and controls. There was a 6.6% (95% CI –2.2% to 15.4%) difference per protocol and 9.9% (95%CI –4.1% to 23.9%) modified intention-to-treat difference in unfavourable responses between the control and 6Pa200MZ arms. Grade 3+ adverse events affected 68/203 (33.5%) receiving experimental regimens, and 19/68 (27.9%) on control. Ten of 203 (4.9%) participants on experimental arms and 2/68 (2.9%) controls died.
CONCLUSION: PaMZ regimens did not achieve non-inferiority in this under-powered trial. An ongoing evaluation of PMD remains a priority.
Close

Details

Original languageEnglish
Pages (from-to)305-314
Number of pages10
JournalInternational Journal of Tuberculosis and Lung Disease
Volume25
Issue number4
DOIs
Publication statusPublished - 1 Apr 2021

    Research areas

  • Pulmonary and Respiratory Medicine, Infectious Diseases

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

View graph of relations

Related by author

  1. Long Covid in adults discharged from UK hospitals after Covid-19: a prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol

    Sigfrid, L., Drake, T. M., Pauley, E., Jesudason, E. C., Olliaro, P., Lim, W. S., Gillesen, A., Berry, C., Lowe, D. J., McPeake, J., Lone, N., Munblit, D., Cevik, M., Casey, A., Bannister, P., Russell, C. D., Goodwin, L., Ho, A., Turtle, L., O'Hara, M. E. & 18 others, Hastie, C., Donohue, C., Spencer, R. G., Donegan, C., Gummery, A., Harrison, J., Hardwick, H. E., Hastie, C. E., Carson, G., Merson, L., Baillie, J. K., Openshaw, P., Harrison, E. M., Docherty, A. B., Semple, M. G., Scott, J. T., ISARIC global follow-up working group & ISARIC4C investigators, Sep 2021, In: The Lancet Regional Health - Europe. 8, 13 p., 100186.

    Research output: Contribution to journalArticlepeer-review

  2. Unlocking the health system barriers to maximise the uptake and utilisation of molecular diagnostics in low- and middle- income country setting

    Ntinginya, N. E., Kuchaka, D., Orina, F., Mwebaza, I., Liyoyo, A., Miheso, B., Aturinde, A., Njeleka, F., Kiula, K., Msoka, E. F., Meme, H., Sanga, E., Mwanyonga, S., Olomi, W., Minja, L., Joloba, M., Mmbaga, B. T., Amukoye, E., Gillespie, S. H. & Sabiiti, W., 24 Aug 2021, In: BMJ Global Health. 6, 8, 12 p., e005357.

    Research output: Contribution to journalArticlepeer-review

  3. Qualitative assessment of the impact of socioeconomic and cultural barriers on uptake and utilisation of tuberculosis diagnostic and treatment tools in East Africa: a cross-sectional study

    Msoka, E. F., Orina, F., Sanga, E., Miheso, B., Mwanyonga, S., Meme, H., Kiula, K., Liyoyo, A., Mwebaza, I., Aturinde, A., Joloba, M., Mmbaga, B. T., Amukoye, E., Ntinginya, N. E., Gillespie, S. H. & Sabiiti, W., 12 Jul 2021, In: BMJ Open. 11, 7, 9 p., e050911.

    Research output: Contribution to journalArticlepeer-review

  4. Networks of SARS-CoV-2 transmission

    Cevik, M. & Baral, S. D., 9 Jul 2021, In: Science. p. 162-163

    Research output: Contribution to journalLetterpeer-review

  5. Aims and challenges of building national trainee networks in clinical microbiology and infectious disease disciplines

    Dellière, S., Peiffer-Smadja, N., João-Lopes, M., Cevik, M., Pichon, M., Bleibtreu, A., Schweitzer, V., Last, K., Ferreira, T. G., Lemaignen, A. & Barac, A., Jul 2021, In: Future Microbiology. Epub ahead of print, 9 p., fmb-2021-0045.

    Research output: Contribution to journalArticlepeer-review

Related by journal

  1. NAT2 variants and toxicity related to anti-tuberculosis agents: a systematic review and meta-analysis

    Richardson, M., Kirkham, J., Dwan, K., Sloan, D. J., Davies, G. & Jorgensen, A. L., 1 Mar 2019, In: International Journal of Tuberculosis and Lung Disease. 23, 3, p. 293-305 13 p.

    Research output: Contribution to journalArticlepeer-review

  2. Optimising molecular diagnostic capacity for effective control of tuberculosis in high-burden settings

    Sabiiti, W., Mtafya, B., Kuchaka, D., Azam, K., Viegas, S., Mdolo, A., Farmer, E., Khonga, M., Evangelopoulos, D., Honeyborne, I., Rachow, A., Heinrich, N., Ntinginya, N. E., Bhatt, N., Davies, G. R., Jani, I. V., McHugh, T. D., Kibiki, G., Hoelscher, M., Gillespie, S. H. & 1 others, PANBIOME (Pan-African Biomarker Expansion Programme) consortium, 1 Aug 2016, In: International Journal of Tuberculosis and Lung Disease. 20, 8, p. 1004-1009

    Research output: Contribution to journalArticlepeer-review

  3. Equitable tuberculosis care in the North West of England: analysis of tuberculosis cohort review data

    MacPherson, P., Squire, S. B., Cleary, P., Davies, S., Wake, C., Dee, K., Walker, J., Farrow, S., McMaster, P., Woodhead, M., Sloan, D. J. & North West TB Audit Steering Committee, 1 Jun 2016, In: International Journal of Tuberculosis and Lung Disease. 20, 6, p. 778-785 8 p.

    Research output: Contribution to journalArticlepeer-review

Related by journal

  1. International Journal of Tuberculosis and Lung Disease (Journal)

    Stephen Henry Gillespie (Editor)

    2011

    Activity: Publication peer-review and editorial work typesEditor of research journal

ID: 273672846

Top