High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial

The Lancet Infectious Diseases

Volumn 17, Issue 1, 2017, Pages 39-49

  Boeree, Martin J ^a   Heinrich, Norbert ^b,c   Aarnoutse, Rob ^a   Diacon, Andreas H ^d   Dawson, Rodney ^f   Rehal, Sunita ⁿ   Kibiki, Gibson S ^g   Churchyard, Gavin ^p,q,s   Sanne, Ian ^r   Ntinginya, Nyanda E ⁱ   Minja, Lilian T ^l   Hunt, Robert D ^m   Charalambous, Salome ^p   Hanekom, Madeleine ^d   Semvua, Hadija H ^g   Mpagama, Stellah G ^h   Manyama, Christina ⁱ   Mtafya, Bariki ⁱ   Reither, Klaus ^j,k   Wallis, Robert S ^p   Venter, Amour ^e   Narunsky, Kim ^f   Mekota, Anka ^b   Henne, Sonja ^b   Colbers, Angela ^a   van Balen, Georgette Plemper ^a   Gillespie, Stephen H ^o   Phillips, Patrick P J ⁿ   Hoelscher, Michael ^b,c   more..

^a RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^b LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^c DZHK (German Centre for Cardiovascular Research)   (Germany)

^d UNIVERSITY OF STELLENBOSCH   (South Africa)

^e STELLENBOSCH UNIVERSITY   (South Africa)

^f UNIVERSITY OF CAPE TOWN   (South Africa)

^g KILIMANJARO CHRISTIAN MEDICAL CENTRE   (Tanzania)

^h Kibong'Oto National Tuberculosis Hospital   (Tanzania)

ⁱ NATIONAL INSTITUTE FOR MEDICAL RESEARCH   (Tanzania)

^j SWISS TROPICAL AND PUBLIC HEALTH INSTITUTE   (Switzerland)

^k UNIVERSITY OF BASEL   (Switzerland)

^l IFAKARA HEALTH INSTITUTE   (Tanzania)

^m UNIVERSITY COLLEGE LONDON   (United Kingdom)

ⁿ MRC CLINICAL TRIALS UNIT   (United Kingdom)

^o UNIVERSITY OF ST ANDREWS   (United Kingdom)

^p AURUM INSTITUTE   (South Africa)

^q UNIVERSITY OF THE WITWATERSRAND   (South Africa)

^r HELEN JOSEPH HOSPITAL   (South Africa)

^s LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE   (United Kingdom)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ETHAMBUTOL; ISONIAZID; MOXIFLOXACIN; N (2 ADAMANTYL) N' GERANYLETHYLENEDIAMINE; PYRAZINAMIDE; RIFAMPICIN; ADAMANTANE; ETHYLENEDIAMINE DERIVATIVE; N-GERANYL-N'-(2-ADAMANTYL)ETHANE-1,2-DIAMINE; QUINOLONE DERIVATIVE; TUBERCULOSTATIC AGENT;

ADULT; AFRICA; ANTIBIOTIC RESISTANCE; ARTICLE; CD4 LYMPHOCYTE COUNT; CONTROLLED STUDY; DOSE RESPONSE; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; FEMALE; FOLLOW UP; HEALTH CENTER; HUMAN; LUNG TUBERCULOSIS; MAJOR CLINICAL STUDY; MALE; MINIMUM INHIBITORY CONCENTRATION; MULTICENTER STUDY; OPEN STUDY; OUTCOME ASSESSMENT; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SPUTUM CULTURE; TANZANIA; TREATMENT DURATION; TREATMENT FAILURE; UNSPECIFIED SIDE EFFECT; ANALOGS AND DERIVATIVES; CLINICAL TRIAL; COMBINATION DRUG THERAPY; DRUG ADMINISTRATION; SOUTH AFRICA; TUBERCULOSIS, PULMONARY;

ADAMANTANE; ADULT; ANTITUBERCULAR AGENTS; DRUG ADMINISTRATION SCHEDULE; DRUG THERAPY, COMBINATION; ETHAMBUTOL; ETHYLENEDIAMINES; FEMALE; FLUOROQUINOLONES; HUMANS; ISONIAZID; MALE; PYRAZINAMIDE; RIFAMPIN; SOUTH AFRICA; TANZANIA; TUBERCULOSIS, PULMONARY;

EID: 85006078193     PISSN: 14733099     EISSN: 14744457     Source Type: Journal    
DOI: 10.1016/S1473-3099(16)30274-2     Document Type: Article

References (35)

1. 1 Fox, W, Ellard, GA, Mitchison, DA, Studies on the treatment of tuberculosis undertaken by the British Medical Research Council tuberculosis units, 1946–1986, with relevant subsequent publications. Int J Tuberc Lung Dis 3 (1999), S231–S279.
2. 2 van Ingen, J, Aarnoutse, RE, Donald, PR, et al. Why do we use 600 mg of rifampicin in tuberculosis treatment?. Clin Infect Dis 52 (2011), e194–e199.
3. 3 de Steenwinkel, JE, Aarnoutse, RE, de Knegt, GJ, et al. Optimization of the rifampin dosage to improve the therapeutic efficacy in tuberculosis treatment using a murine model. Am J Respir Crit Care Med 187 (2013), 1127–1134.
4. 4 Hu, Y, Liu, A, Ortega-Muro, F, Alameda-Martin, L, Mitchison, D, Coates, A, High-dose rifampicin kills persisters, shortens treatment duration, and reduces relapse rate in vitro and in vivo. Front Microbiol, 6, 2015, 641.
5. 5 Rosenthal, IM, Tasneen, R, Peloquin, CA, et al. Dose-ranging comparison of rifampin and rifapentine in two pathologically distinct murine models of tuberculosis. Antimicrob Agents Chemother 56 (2012), 4331–4340.
6. 6 Jayaram, R, Gaonkar, S, Kaur, P, et al. Pharmacokinetics-pharmacodynamics of rifampin in an aerosol infection model of tuberculosis. Antimicrob Agents Chemother 47 (2003), 2118–2124.
7. 7 Steingart, KR, Jotblad, S, Robsky, K, et al. Higher-dose rifampin for the treatment of pulmonary tuberculosis: a systematic review. Int J Tuberc Lung Dis 15 (2011), 305–316.
8. 8 Boeree, MJ, Diacon, AH, Dawson, R, et al. A dose-ranging trial to optimize the dose of rifampin in the treatment of tuberculosis. Am J Respir Crit Care Med 191 (2015), 1058–1065.
9. 9 Boeree MJ. High-dose rifampicin: issues in efficacy and safety. The 46th Union World Conference on Lung Health; Cape Town; Dec 6, 2015.
10. 10 Phillips, PP, Gillespie, SH, Boeree, M, et al. Innovative trial designs are practical solutions for improving the treatment of tuberculosis. J Infect Dis 205:suppl 2 (2012), S250–S257.
11. 11 James, ND, Sydes, MR, Mason, MD, et al. Celecoxib plus hormone therapy versus hormone therapy alone for hormone-sensitive prostate cancer: first results from the STAMPEDE multiarm, multistage, randomised controlled trial. Lancet Oncol 13 (2012), 549–558.
12. 12 Sacksteder, KA, Protopopova, M, Barry, CE 3rd, Andries, K, Nacy, CA, Discovery and development of SQ109: a new antitubercular drug with a novel mechanism of action. Future Microbiol 7 (2012), 823–837.
13. 13 Heinrich, N, Dawson, R, du Bois, J, et al. Early phase evaluation of SQ109 alone and in combination with rifampicin in pulmonary TB patients. J Antimicrob Chemother 70 (2015), 1558–1566.
14. 14 Rustomjee, R, Lienhardt, C, Kanyok, T, et al. A phase II study of the sterilising activities of ofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. Int J Tuberc Lung Dis 12 (2008), 128–138.
15. 15 Gillespie, SH, Crook, AM, McHugh, TD, et al. Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis. N Engl J Med 371 (2014), 1577–1587.
16. 16 Conde, MB, Efron, A, Loredo, C, et al. Moxifloxacin versus ethambutol in the initial treatment of tuberculosis: a double-blind, randomised, controlled phase II trial. Lancet 373 (2009), 1183–1189.
17. 17 Guideline for Good Clinical Practice, 2002, EMEA, London.
18. 18 Program NTC DoH. The South African national tuberculosis control programme practical guidelines, 2004, Department of Health, Pretoria.
19. 19 FDA. E14 clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs, 2005, US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Rockville, MD.
20. 20 Common Terminology Criteria for Adverse Events (CTCAE), 2010, National Institutes of Health, Bethesda, MD.
21. 21 Dawson, R, Diacon, AH, Everitt, D, et al. Efficiency and safety of the combination of moxifloxacin, pretomanid (PA-824), and pyrazinamide during the first 8 weeks of antituberculosis treatment: a phase 2b, open-label, partly randomised trial in patients with drug-susceptible or drug-resistant pulmonary tuberculosis. Lancet 385 (2015), 1738–1747.
22. 22 Dorman, SE, Savic, RM, Goldberg, S, et al. Daily rifapentine for treatment of pulmonary tuberculosis. A randomized, dose-ranging trial. Am J Respir Crit Care Med 191 (2015), 333–343.
23. 23 Nijland, HM, Ruslami, R, Suroto, AJ, et al. Rifampicin reduces plasma concentrations of moxifloxacin in patients with tuberculosis. Clin Infect Dis 45 (2007), 1001–1007.
24. 24 Musuka, S, Srivastava, S, Siyambalapitiyage Dona, CW, et al. Thioridazine exhibits wobbly pharmacokinetic-pharmacodynamic parameters during treatment of tuberculosis: a theoretical basis for shorter duration curative monotherapy with congeners. Antimicrob Agents Chemother 57 (2013), 5870–5877.
25. 25 Sloan DJ, Mwandumba HC, Garton NJ, et al. Pharmacodynamic modeling of bacillary elimination rates and detection of bacterial lipid bodies in sputum to predict and understand outcomes in treatment of pulmonary tuberculosis. Clin Infect Dis; 61: 1–8.
26. 26 Prideaux, B, Via, LE, Zimmerman, MD, et al. The association between sterilizing activity and drug distribution into tuberculosis lesions. Nat Med 21 (2015), 1223–1227.
27. 27 Bowness, R, Boeree, MJ, Aarnoutse, R, et al. The relationship between Mycobacterium tuberculosis MGIT time to positivity and cfu in sputum samples demonstrates changing bacterial phenotypes potentially reflecting the impact of chemotherapy on critical sub-populations. J Antimicrob Chemother 70 (2015), 448–455.
28. 28 Kayigire, XA, Friedrich, SO, van der Merwe, L, Donald, PR, Diacon, AH, Simultaneous staining of sputum smears for acid-fast and lipid-containing Myobacterium tuberculosis can enhance the clinical evaluation of antituberculosis treatments. Tuberculosis (Edinb) 95 (2015), 770–779.
29. 29 Dhillon, J, Fourie, PB, Mitchison, DA, Persister populations of Mycobacterium tuberculosis in sputum that grow in liquid but not on solid culture media. J Antimicrob Chemother 69 (2014), 437–440.
30. 30 Acocella, G, Clinical pharmacokinetics of rifampicin. Clin Pharmacokinet 3 (1978), 108–127.
31. 31 Gumbo, T, Louie, A, Deziel, MR, et al. Concentration-dependent Mycobacterium tuberculosis killing and prevention of resistance by rifampin. Antimicrob Agents Chemother 51 (2007), 3781–3788.
32. 32 Heemskerk, AD, Bang, ND, Mai, NT, et al. Intensified antituberculosis therapy in adults with tuberculous meningitis. N Eng J Med 374 (2016), 124–134.
33. 33 Chigutsa, E, Visser, ME, Swart, EC, et al. The SLCO1B1 rs4149032 polymorphism is highly prevalent in South Africans and is associated with reduced rifampin concentrations: dosing implications. Antimicrob Agents Chemother 55 (2011), 4122–4127.
34. 34 Phillips, PP, Dooley, KE, Gillespie, SH, et al. A new trial design to accelerate tuberculosis drug development: the phase IIC selection trial with extended post-treatment follow-up (STEP). BMC Med, 14, 2016, 51.
35. 35 Honeyborne, I, Mtafya, B, Phillips, PP, et al. The molecular bacterial load assay replaces solid culture for measuring early bactericidal response to antituberculosis treatment. J Clin Microbiol 52 (2014), 3064–3067.