Essentiality of INH in TB Therapy

Summary

Tuberculosis (TB) disease is caused by bacteria that have infected the lung. TB bacteria are very small living agents that are spread by coughing and can be killed by taking TB drugs. To kill these TB bacteria TB patients have to take a combination of four drugs for 2 months and then two drugs for a further 4 months. During the first 2 months patients take rifampicin, isoniazid, ethambutol, and pyrazinamide. After that patients take only isoniazid and rifampicin for a further 4 months, making a total of 6 months therapy.

In A5307 the investigators wanted to test a new combination of drugs to see if the investigators could treat TB faster in the future.

Studies in animals have suggested that one of the four drugs, isoniazid, only works for a few days and may not be needed after the first two doses of TB treatment to kill the TB bacteria. After that its effects wear off to the point that it may even interfere with the other drugs. The investigators wanted to see if stopping isoniazid early, or using moxifloxacin, a different drug, instead could treat TB faster. This study was the first time that this type of regimen without isoniazid had been tested in humans. If the investigators could show that isoniazid stops working after a few days, the investigators could then try to see if they could possibly make a better tuberculosis treatment in the future.

Conditions

• Tuberculosis

Interventions

DRUG

Rifampicin

Participants with body weight \</= 50kg were administered one 450 mg tablet orally once daily. Participants with body weight \>50kg were administered one 600 mg tablet orally once daily.

DRUG

Isoniazid

Participants were administered three 100 mg tablets or one 300 mg tablet once daily.

DRUG

Pyrazinamide

Participants with a body weight of 40-55 kg were administered two 500 mg tablets orally once daily. Participants with a body weight of 56-75 kg were administered three 500 mg tablets orally once daily. Participants with a body weight of 76-90 kg were administered four 500 mg tablets orally once daily.

DRUG

Ethambutol

Participants with a body weight of 40-55 kg were administered two 400 mg tablets orally once daily. Participants with a body weight of 56-75 kg were administered three 400 mg tablets orally once daily. Participants with a body weight of 76-90 kg were administered four 400 mg tablets orally once daily.

DRUG

Moxifloxacin

Participants were administered one 400 mg tablet orally once a day.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

  collaborator NIH

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

  lead NETWORK

Principal Investigators

• William Bishai, MD, PhD · Johns Hopkins Center for TB Research

• Andreas Diacon, MD, PhD · TASK Applied Science CRS

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-06-30

Primary Completion

2016-01-28

Completion

2016-02-10

Countries

• South Africa

Study Locations