Treatment of Latent Tuberculosis Infection With Isoniazid

Secretariat of Health

Status and phase: Completed; Phase 4

Conditions: Tuberculosis

Treatments: Drug: isoniazid; Drug: Isoniazid

Study type: Interventional

Funder types: Other

Identifiers

NCT00293228

137

Details and patient eligibility

About

The purpose of this study is to study the effect that treatment of dormant tuberculosis infection has on the immunological system.

We expect to observe an impact over the production of cytokines by peripheral white blood cells which may be useful to know if treatment has been effective.

Full description

As part of on-going studies conducted in the Orizaba Health Jurisdiction in southeastern Mexico, household contacts of pulmonary TB patients who recently converted their tuberculin test and TST+ve contacts from randomly selected control households with no history of TB within the last 2 years (remote contacts) will be enrolled. We assume that these individuals are infected with Mycobacterium tuberculosis. Additional confidence that all subjects enrolled are latently infected will come from ELISPOT analysis of the response to ESAT-6 and CFP-10. We propose to administer INH to 100 TST+ve recent and 100 TST+ve remote contacts for 6 months. To control for spontaneous fluctuations of biomarker levels, we propose to defer therapy by 3 months to half the subjects in each group. Thus, four groups will be defined:

A. Recently converted contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) immediately after recruitment.

B. Recently converted contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) three months after recruitment.

C. Remote contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) immediately after recruitment.

D. Remote contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) three months after recruitment.

All contacts will undergo clinical evaluation at enrolment and review. The development of active TB will trigger withdrawal and full treatment. Fortnightly clinical review of group B during the deferred phase will be undertaken. ELISPOT analysis will be performed on all subjects at 0, 1, 4, 13, 26 and 40 weeks in groups A and C, and at 0, 13, 14, 17, 26, 40 and 54 weeks in groups B and D. A subset of 10 patients per group will be sampled for expression analysis at 0, 4, 26 and 40 weeks (groups A and C) and at 0, 13, 17 and 40 weeks in groups B and D (160 hybridizations in total).

Enrollment: 200 estimated patients

Sex: All

Ages: 10 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Informed consent
• Age 10-45
• Either sex
• Resident in study area
• Documented TST+ve (>10mm, Mantoux method, 2TU, PPD Statens Serum Institute)
• Normal chest radiograph
• HIV negative test

Exclusion criteria

• Active tuberculosis
• Previous diagnosis of tuberculosis
• Treatment for active or latent tuberculosis
• Contact with TB patients harboring MDR or INH resistant isolates of Mtb
• Diseases or therapies associated with immunosuppression
• Diabetes mellitus
• Abnormal liver enzyme levels.
• HB below 8gr/dl
• Pregnancy (ascertained by urinary β-HCG)
• Allergy or intolerance to isoniazid
• Peripheral neuropathy
• Ingestion of drugs interacting with isoniazid

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 4 patient groups

A

Experimental group

Description:

Recently converted contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) immediately after recruitment.

Treatment:

Drug: Isoniazid

B

Active Comparator group

Description:

B. Recently converted contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) three months after recruitment.

Treatment:

Drug: Isoniazid

C

Experimental group

Description:

C. Remote contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) immediately after recruitment

Treatment:

Drug: Isoniazid

D

Active Comparator group

Description:

D. Remote contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) three months after recruitment.

Treatment:

Drug: Isoniazid