There is an urgent need for novel therapies to shorten TB treatment and improve long-term
lung function outcomes. Host-directed therapies (HDT) have received significant attention
recently given the ability of M. tuberculosis to subvert host immune responses and cause
destructive lung pathology. Statins are among the most promising HDT agents for TB. In
addition to having a highly favorable safety profile, statins have been shown to have anti-TB
activity in macrophages, to synergize with anti-TB drugs, and to shorten the duration of TB
treatment in the standard mouse model.
The StAT-TB trial will comprise two different stages. In the 14-day Stage 1 study,
investigators will test the safety and tolerability, as well as Pharmacokinetics (PK), of two
different doses of pravastatin co-administered with standard anti-TB treatment. In Stage 2,
investigators will test the ability of pravastatin adjunctive therapy (dose to be determined
in Stage 1) to shorten the mean time to sputum culture conversion (primary endpoint) and
improve lung function outcomes (secondary endpoints) relative to the standard regimen. In
addition, investigators will continue to investigate the anti-TB mechanism of action of
pravastatin in order to further improve HDT options for TB in the future.