Clinical trial NCT00216385: A Controlled Trial of a 4-Month Quinolone-Containing Regimen for the Treatment of Pulmonary Tuberculosis
Official title: A Randomised Open-Label Controlled Trial of a 4-Month Gatifloxacin-Containing Regimen Versus Standard Regimen for the Treatment of Adult Patients With Pulmonary Tuberculosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Tuberculosis
Keywords: Tuberculosis
Treatment
Quinolone
Short course chemotherapy
Lead sponsor: Institut de Recherche pour le Developpement
Sponsor class: OTHER_GOV
Collaborators: name: World Health Organization
name: European Commission
First posted: 2005-09-22
Enrollment: 2070
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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,

Detailed description: In order to evaluate the efficacy and safety of the 4-month test gatifloxacin-containing regimen, comparison will be made with a standard 6-month regimen, recommended by WHO. Patients will be treated with one of the two regimens that will be randomly allocated. A total of 2070 patients will ne recruited in the trial and followed-up for a duration of 2 years. The trial is multicentre, and conducted in 5 countries in Africa.

Eligibility criteria: Inclusion Criteria:

* Male or female patients
* Aged 18 to 65 years
* Currently suffering from recently diagnosed microscopically proven pulmonary tuberculosis and providing informed consent for inclusion in the study.

Exclusion Criteria:

* Patients with history of tuberculosis treatment within the last 3 years
* History of diabetes mellitus or non insulin dependent diabetes mellitus requiring treatment
* Concomitant infection requiring additional anti-infective treatment (especially anti-retroviral therapy)
* HIV infected patients with WHO stage 3 infection - except those presenting with only the "loss of weight\>10% body weight" criterion - and all HIV infected patients at WHO stage 4.

Primary outcomes:
measure: Efficacy: Percentage of relapses by 24 months following treatment cure
measure: Safety: Percentage of adverse events
Secondary outcomes:
measure: Efficacy: Time to relapse
measure: Efficacy: Percentage of smear and culture conversion at 8 weeks
measure: Efficacy: Percentage of patient cured at the end of treatment
measure: Efficacy: Time to a composite "unsatisfactory" endpoint
measure: Safety outcome: Distribution of type and grading of adverse events
Other outcomes:
Locations:
city: Cotonou
country: Benin
facility: Programme National de Lutte contre la Tuberculose
city: Conakry
country: Guinea
facility: Service Pneumo-Phtisiologie, CHU Ignace Deen
city: Nairobi
country: Kenya
facility: Kenya Medical Research Institute
city: Dakar
country: Senegal
facility: Programme National de Lutte contre la Tuberculose
city: Durban
country: South Africa
facility: Medical Research Council
state: KwaZulu
Study officials:
affiliation: Institut de Recherche pour le Developpement
name: Christian Lienhardt, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.