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Multicenter Trial for the Evaluation of a Fixed Dose Combined Tablet for the Treatment of Pulmonary Tuberculosis

Phase 4
Conditions
Tuberculosis
Registration Number
NCT00216333
Lead Sponsor
International Union Against Tuberculosis and Lung Diseases
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)

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
1500
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
Efficacy : combined rate of failure at the end of treatment and relapse by 30 months.
Safety : occurrence of serious adverse events at any time during chemotherapy
Secondary Outcome Measures
NameTimeMethod
Sputum culture results at two months of chemotherapy
Rate of completion of chemotherapy according to the protocol

Trial Locations

Locations (9)

Centro Internacional de Entrenamiento

🇨🇴

Cali, Colombia

Grupo Levir S.A.

🇵🇪

Lima, Peru

Service de Pneumo-phtisiologie de Matiben

🇩🇿

Algiers, Algeria

Program Nal. de Control de la Tuberculosis

🇧🇴

Santa Cruz, Bolivia

CHU Ignace Deen

🇬🇳

Conakry, Guinea

Health Resesarch Center of Manhica

🇲🇿

Manhica, Mozambique

Nepal Anti-Tuberculosis Association

🇳🇵

Kathmandu, Nepal

National Institute for Medical Research

🇹🇿

Mwanza, Tanzania

National Hospital of TB and Respiratory Diseases

🇻🇳

Hanoi, Vietnam

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