Clinical trial NCT00216333: Multicenter Trial for the Evaluation of a Fixed Dose Combined Tablet for the Treatment of Pulmonary Tuberculosis
Official title: International Multicenter Trial for the Evaluation of a Four-Drug Fixed Dose Combined Tablet Daily in the Initial Intensive Phase of Chemotherapy Followed by a Two-Drug Fixed Dose Combined Tablet Three Times a Week in the Continuation Phase for the Treatment of Pulmonary Tuberculosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Tuberculosis
Keywords: tuberculosis
fixed dose combination
DOT
shot-course chemotherapy
Lead sponsor: International Union Against Tuberculosis and Lung Diseases
Sponsor class: OTHER
Collaborators: name: United States Agency for International Development (USAID)
First posted: 2005-09-22
Enrollment: 1500
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: The use of fixed-dose combined (FDC) drugs in the treatment of tuberculosis by National Tuberculosis Programmes has been recommended by both the International Union Against Tuberculosis and Lung Disease (The Union) and the World Health Organisation. The advantages of FDC drugs include preventing the emergence of drug resistance due to monotherapy, reducing the risk of incorrect dosage, simplifying procurement and prescribing practices, aiding adherence and facilitating directly observed treatment. Recent bioavailability studies of four-drug FDC tablets have demonstrated satisfactory results. In this study, we are testing the efficacy of this compound, when given in the initial intensive phase of treatment of patients with newly diagnosed smear positive pulmonary tuberculosis. This will be followed by four months treatment with a two-drug FDC of rifampicin and isoniazid.

Detailed description: This is a multiple country, multicenter study, using the parallel group open-label randomised trial design. The primary objective of this investigation is to assess the efficacy, acceptability and toxicity of a combined FDC regimen of chemotherapy in patients with newly diagnosed smear positive pulmonary tuberculosis in comparison with the standard regimen using separate drugs.

Patients will be allocated at random either :

* an initial intensive phase of eight weeks of daily ethambutol, isoniazid, rifampicin and pyrazinamide, in a fixed dose COMBINED tablet, followed by 18 weeks of rifampicin and isoniazid, in a fixed dose combined tablet three times a week (2COMB/4(RH)3) or
* the same drugs given in SEPARATE formulations in the initial intensive phase of eight weeks, followed by 18 weeks of rifampicin and isoniazid, in a fixed dose combined tablet, three times a week (2SEPA/4(RH)3)

Eligibility criteria: Inclusion Criteria:

* Patients with newly diagnosed pulmonary tuberculosis
* two sputum specimens positive for acid-fast bacilli on direct smear microscopy
* no previous anti-tuberculosis chemotherapy
* aged 18 years and over
* firm home address that is readily accessible for visiting for the duration of the trial (including follow up period)
* agree to participate in the study and to give a sample of blood for HIV test

Exclusion Criteria:

* patients in a moribund state,
* TB meningitis,
* pre-existing diseases: insulin-dependent diabetes, liver or kidney disease, blood disorders, peripheral neuritis,
* pregnancy or breast feeding,
* psychiatric illness
* alcoholism
* contraindication to any medications in the study regimens

Primary outcomes:
measure: Efficacy : combined rate of failure at the end of treatment and relapse by 30 months.
measure: Safety : occurrence of serious adverse events at any time during chemotherapy
Secondary outcomes:
measure: Sputum culture results at two months of chemotherapy
measure: Rate of completion of chemotherapy according to the protocol
Other outcomes:
Locations:
city: Algiers
country: Algeria
facility: Service de Pneumo-phtisiologie de Matiben
city: Santa Cruz
country: Bolivia
facility: Program Nal. de Control de la Tuberculosis
city: Cali
country: Colombia
facility: Centro Internacional de Entrenamiento
city: Conakry
country: Guinea
facility: CHU Ignace Deen
city: Manhica
country: Mozambique
facility: Health Resesarch Center of Manhica
city: Kathmandu
country: Nepal
facility: Nepal Anti-Tuberculosis Association
city: Lima
country: Peru
facility: Grupo Levir S.A.
city: Mwanza
country: Tanzania
facility: National Institute for Medical Research
city: Hanoi
country: Vietnam
facility: National Hospital of TB and Respiratory Diseases
Study officials:
affiliation: International Union Against Tuberculosis and Lung Diseases
name: Christian Lienhardt, MD
role: STUDY_DIRECTOR
References:
citation: Lienhardt C, Cook SV, Burgos M, Yorke-Edwards V, Rigouts L, Anyo G, Kim SJ, Jindani A, Enarson DA, Nunn AJ; Study C Trial Group. Efficacy and safety of a 4-drug fixed-dose combination regimen compared with separate drugs for treatment of pulmonary tuberculosis: the Study C randomized controlled trial. JAMA. 2011 Apr 13;305(14):1415-23. doi: 10.1001/jama.2011.436.