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.
Timeline
- Start
- 2015-06-30
- Primary completion
- 2016-01-28
- Completion
- 2016-02-10
Publications
- Background The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009).
- Diacon A, Miyahara S, Dawson R, Sun X, Hogg E, Donahue K, Urbanowski M, De Jager V, Fletcher CV, Hafner R, Swindells S, Bishai W. Assessing whether isoniazid is essential during the first 14 days of tuberculosis therapy: a phase 2a, open-label, randomised controlled trial. Lancet Microbe. 2020 Jun;1(2):e84-e92. doi: 10.1016/s2666-5247(20)30011-2. Epub 2020 Jun 8.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Isoniazid | Small molecule | 300 mg | — |
| Comparator | Moxifloxacin | Small molecule | 400 mg | Oral |
| Comparator | Ethambutol | Small molecule | 800 mg | Oral |
| Comparator | Ethambutol | Small molecule | 1200 mg | Oral |
| Comparator | Ethambutol | Small molecule | 1600 mg | Oral |
| Comparator | Pyrazinamide | Small molecule | 1000 mg | Oral |
| Comparator | Pyrazinamide | Small molecule | 1500 mg | Oral |
| Comparator | Pyrazinamide | Small molecule | 2000 mg | Oral |
| Comparator | Rifampin | Small molecule | 450 mg | Oral |
| Comparator | Rifampin | Small molecule | 600 mg | Oral |