A Controlled Trial of a 4-Month Quinolone-Containing Regimen for the Treatment of Pulmonary Tuberculosis

Summary

Tuberculosis is currently treated with a 6-month course regimen. During this time many patients might fail to adhere to treatment and default, increasing the risk of recurrent disease which might be multidrug resistant. A shorter duration of treatment is expected to provide improved patient compliance and at least equal or better clinical outcome. The aim of the trial is to evaluate the efficacy and safety of a gatifloxacin-containing regimen of four months duration for the treatment of pulmonary tuberculosis,

Timeline

Start

2005-01

Primary completion

—

Completion

2008-12

Outcome

Missed primary endpoint

paper Noninferiority of the 4-month regimen to the standard regimen with respect to the primary efficacy end point was not shown. PMID 25337748 ↗

Publications

• Pasipanodya JG, Smythe W, Merle CS, Olliaro PL, Deshpande D, Magombedze G, McIlleron H, Gumbo T. Artificial intelligence-derived 3-Way Concentration-dependent Antagonism of Gatifloxacin, Pyrazinamide, and Rifampicin During Treatment of Pulmonary Tuberculosis. Clin Infect Dis. 2018 Nov 28;67(suppl_3):S284-S292. doi: 10.1093/cid/ciy610.
• Olliaro PL, Merle C, Mthiyane T, Bah B, Kassa F, Amukoye E, N Diaye A, Perronne C, Lienhardt C, McIlleron H, Fielding K. Effects on the QT Interval of a Gatifloxacin-Containing Regimen versus Standard Treatment of Pulmonary Tuberculosis. Antimicrob Agents Chemother. 2017 Jun 27;61(7):e01834-16. doi: 10.1128/AAC.01834-16. Print 2017 Jul.
• Merle CS, Fielding K, Sow OB, Gninafon M, Lo MB, Mthiyane T, Odhiambo J, Amukoye E, Bah B, Kassa F, N'Diaye A, Rustomjee R, de Jong BC, Horton J, Perronne C, Sismanidis C, Lapujade O, Olliaro PL, Lienhardt C; OFLOTUB/Gatifloxacin for Tuberculosis Project. A four-month gatifloxacin-containing regimen for treating tuberculosis. N Engl J Med. 2014 Oct 23;371(17):1588-98. doi: 10.1056/NEJMoa1315817.
• Smythe W, Merle CS, Rustomjee R, Gninafon M, Lo MB, Bah-Sow O, Olliaro PL, Lienhardt C, Horton J, Smith P, McIlleron H, Simonsson US. Evaluation of initial and steady-state gatifloxacin pharmacokinetics and dose in pulmonary tuberculosis patients by using monte carlo simulations. Antimicrob Agents Chemother. 2013 Sep;57(9):4164-71. doi: 10.1128/AAC.00479-13. Epub 2013 Jun 17.
• Merle CS, Sismanidis C, Sow OB, Gninafon M, Horton J, Lapujade O, Lo MB, Mitchinson DA, Perronne C, Portaels F, Odhiambo J, Olliaro P, Rustomjee R, Lienhardt C, Fielding K. A pivotal registration phase III, multicenter, randomized tuberculosis controlled trial: design issues and lessons learnt from the Gatifloxacin for TB (OFLOTUB) project. Trials. 2012 May 18;13:61. doi: 10.1186/1745-6215-13-61.

Drugs

Indications