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

Tuberculosis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00216333
• Other study ID #: IUATLD CT Study C
• Status: Recruiting
• Phase: Phase 4
• First received: September 20, 2005
• Last updated: September 12, 2006
• Start date: December 2003
• Est. completion date: June 2007

Study information

• Verified date: September 2006
• Source: International Union Against Tuberculosis and Lung Diseases
• Contact: Sharlette Cook, MPH
• Phone: +33 1 44 32 06 47
• Email: scook[@]iuatld.org
• Is FDA regulated: No
• Health authority: France: IUATLD
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 1500
• Est. completion date: June 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Tuberculosis
• Tuberculosis, Pulmonary

Intervention

Drug:
• combined fixed dose combination

Locations

Country	Name	City	State
Algeria	Service de Pneumo-phtisiologie de Matiben	Algiers
Bolivia	Program Nal. de Control de la Tuberculosis	Santa Cruz
Colombia	Centro Internacional de Entrenamiento	Cali
Guinea	CHU Ignace Deen	Conakry
Mozambique	Health Resesarch Center of Manhica	Manhica
Nepal	Nepal Anti-Tuberculosis Association	Kathmandu
Peru	Grupo Levir S.A.	Lima
Tanzania	National Institute for Medical Research	Mwanza
Vietnam	National Hospital of TB and Respiratory Diseases	Hanoi

Sponsors (2)

Lead Sponsor	Collaborator
International Union Against Tuberculosis and Lung Diseases	United States Agency for International Development (USAID)

Countries where clinical trial is conducted

Algeria,  Bolivia,  Colombia,  Guinea,  Mozambique,  Nepal,  Peru,  Tanzania,  Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy : combined rate of failure at the end of treatment and relapse by 30 months.
Primary	Safety : occurrence of serious adverse events at any time during chemotherapy
Secondary	Sputum culture results at two months of chemotherapy
Secondary	Rate of completion of chemotherapy according to the protocol