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

• ClinicalTrials.gov Identifier: NCT00216385
• Recruitment Status: Unknown
• First Posted: September 22, 2005
• Last Update Posted: September 22, 2005
• Sponsor: Institut de Recherche pour le Developpement
• Collaborators: World Health Organization; European Commission
• Information provided by: Institut de Recherche pour le Developpement

Study Description

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,

Condition or disease	Intervention/treatment	Phase
Tuberculosis	Drug: Gatifloxacin combined regimen	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Enrollment: 2070 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: January 2005
• Study Completion Date: December 2008

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Efficacy: Percentage of relapses by 24 months following treatment cure
2. Safety: Percentage of adverse events

Secondary Outcome Measures :

1. Efficacy: Time to relapse
2. Efficacy: Percentage of smear and culture conversion at 8 weeks
3. Efficacy: Percentage of patient cured at the end of treatment
4. Efficacy: Time to a composite "unsatisfactory" endpoint
5. Safety outcome: Distribution of type and grading of adverse events

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Benin

Programme National de Lutte contre la Tuberculose; Recruiting

Cotonou, Benin

Contact: Martin Gninafon, MD + 229 33 15 33 pnt@intnet.bj

Principal Investigator: Martin Gninafon, MD

Guinea

Service Pneumo-Phtisiologie, CHU Ignace Deen; Recruiting

Conakry, Guinea

Contact: Oumou Y Sow, MD +224 41 20 58 prsow@kassa.sotelgui.net.gn

Principal Investigator: Oumou Sow, MD

Kenya

Kenya Medical Research Institute; Recruiting

Nairobi, Kenya

Contact: Joseph Odhiambo, MD + 254 02 71 30 08 jodhiambo@nairobi.mimcom.net

Principal Investigator: Joseph Odhiambo, MD

Senegal

Programme National de Lutte contre la Tuberculose; Recruiting

Dakar, Senegal

Contact: Cheikh Seck, MD + 221 824.90.09 cheikbaf@yahoo.fr

Principal Investigator: Cheikh Seck, MD

South Africa

Medical Research Council; Recruiting

Durban, KwaZulu, South Africa

Contact: Roxana Rustomjee, MD +27 31 207 16 75 Roxana.rustomjee@mrc.ac.za

Principal Investigator: Roxana Rustomjee, MD

Sponsors and Collaborators

Institut de Recherche pour le Developpement

World Health Organization

European Commission

Investigators

• Study Director: Christian Lienhardt, MD; Institut de Recherche pour le Developpement

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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). pii: 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. Erratum in: N Engl J Med. 2015 Apr 23;372(17):1677.

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.

• ClinicalTrials.gov Identifier: NCT00216385
• Other Study ID Numbers: ICA4-CT 2002-10057
• First Posted: September 22, 2005
• Last Update Posted: September 22, 2005
• Last Verified: September 2005

Keywords provided by Institut de Recherche pour le Developpement:

Tuberculosis; Treatment; Quinolone; Short course chemotherapy

Additional relevant MeSH terms:

Tuberculosis; Tuberculosis, Pulmonary; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Gatifloxacin; Anti-Bacterial Agents; Anti-Infective Agents; Ophthalmic Solutions; Pharmaceutical Solutions; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents