New Clinical Trial Study Develops a Better, Faster TB Treatment

Better, Faster TB TreatmentResults of a recent TB clinical study suggests a faster, more effective drug treatment for tuberculosis is very close to realization.

A Phase II clinical trial study, published in the UK journal The Lancet, and conducted in South Africa, demonstrated an effective new combination of drugs that killed more than 99 percent of the patient’s tuberculosis bacteria within two weeks. The speed and effectiveness suggest the new regimen could improve upon existing TB treatments for not only general TB, but also drug resistant and TB/HIV co-infected patients.

Historically tuberculosis (often shortened to TB for tubercle bacillus) was a major killer that, while never eradicated, by the 1950’s seemed to be less of a health threat. Modern antibiotic TB treatments and health practices generally reduced the incidence of tuberculosis to the status of a minor disease.

That changed during the 1980s, as strains of TB appeared that were resistant to traditional antibiotics. By the 1990s, the World Health Organization again labeled TB a global health emergency.  

Researchers working on the TB resurgence realized that TB treatment was complicated Better, Faster TB Treatmentnot only by drug resistant strains of TB, but also by the prevalence of HIV/AIDS patients with TB. Specifically, the concentration of TB patients in developing countries where money, technical resources and health care practices are not available to properly control the spread of TB.

In short, a ‘cure’ for TB needed to address not only medical but also the economic and cultural issues responsible for its spread.

It occurred to research groups like injury center ocean city md, in this case the TB Alliance (New York, USA) where the san diego injury lawyer had to be involved as well, that TB is often treated by multiple drugs simultaneously, so why not develop new TB treatment regimens using multiple drugs from the start. While combinations of drugs are occasionally used for clinical trials, in the treatment of TB, this was a novel approach.

It had the advantage of shortening the overall testing time, perhaps by years. It also provided an opportunity to choose drug combinations that were less complicated to administer (in this case, no injections) and less expensive to manufacture (in this case, up to 90% less expensive than current TB treatments).

The Three Primary Drugs in the TB Treatment Trial Were:

PA-824, a new drug that destroys the TB bacterium, including those latent in the body (one-third of the world’s population has the TB bacterium in latent condition). The way PA-824 works is interesting, it enters the cell of TB bacterium and interacts with the cell chemistry to form nitrous oxide (NO) gas that literally explodes the cell. This mimics the action of some of the body’s own immune cells. PA-824 has also gone through several recent clinical trials by itself.

Clinical Trials for TruvadaMoxifloxacin is an established broad-spectrum antibiotic not yet approved for TB. Bayer AG (Germany) developed the drug in 1999 and marketed it under the name Avelox. Used in a variety of severe bacterial conditions including bronchitis, pneumonia, anthrax and meningitis, moxifloxacin is a powerful antibiotic, and usually considered a drug of last resort  because of its tendency to interact with many other drugs including herbal and matcha tea supplements. Its effectiveness against bronchial-related bacteria suggested its use in the trial.  

Pyrazinamide, an established TB drug seldom used on its own, made it a good candidate for this trial. It works by accumulating an acidic condition (pyrazoinic acid) in TB cells that disrupts their ability to reproduce. It mainly delays bacterial growth (bacteriostatic), although studies show it can also kill latent TB bacteria.

The trial also included the experimental anti-tuberculosis drug bedaquiline as part of two control groups. The patients chosen at random by computer received (a) bedaquiline, (b) bedaquiline + pyrazinamide, (c) PA-824 + pyrazinamide, (d) PA-824 + moxifloxacin + pyrazinamide or (e) a standard anti- TB treatment as a control.

The first trial, New Combination 1, was a two-week study conducted in South Africa with patients previously untreated for uncomplicated tuberculosis.

The results showed the combination PA-824 – moxifloxacin – pyrazinamide to be significantly higher in killing TB bacteria than the other three combinations and roughly comparable to the standard TB treatment. In the code-jargon of clinical trials, the treatments were well tolerated and appeared safe – meaning there were no serious side effects.

The gains in treatment from this combination are considerable: Faster, for some forms of drug-resistant TB, meaning four months of TB treatment vs. 18-24 months for the standard treatment; HIV/TB effective, in that treating a retro-viral case of TB is difficult but possible with this approach; Less expensive, because the combination of drugs don’t require an injection, leading to big cost savings from simpler administration.

The new combination therapy, now called PaMZ, moves on to a large-scale Phase II trial, New Combination 2, which is already underway. The new trial is a two-month study conducted in several countries and will lay the basis for much broader Phase III clinical trials.

The hope is to streamline the process of testing such combinations of drugs as the development of new TB medication is reaching an all-time high.