Study type: Randomized Control Treatment Trial
Study population: Male and female patients with ≥15 years of age and acute scrub typhus
Duration: 2 years
Study Design: Prospective, open-label, randomized-controlled treatment trial in patients ≥15
years old admitted to hospital with acute scrub typhus. Randomization into 3 oral treatment
arms (each n=59 patients, total n=177): i) 7 days of doxycycline, ii) 3 days of doxycycline,
and iii) 3 days of azithromycin
Primary Objective: To evaluate the clinical and microbiological responses in scrub typhus
patients to three oral treatment regimens: 7 days of doxycycline, 3 days of doxycycline, and
3 days of azithromycin
Secondary Objectives:
1. To perform pharmacokinetic/pharmacodynamics (PK/PD) characterization of the therapeutic
responses for doxycycline and azithromycin, incl. serial bacterial load measurements.
2. To define clinical, bacterial, pathophysiological and pharmacological factors associated
with disease severity, fever-clearance times (FCT), treatment failures and
relapse/re-infection.
3. To determine the minimum inhibitory concentrations (MIC) of clinical Orientia
tsutsugamushi isolates to doxycycline, azithromycin and chloramphenicol, using in vitro
growth-inhibition assays
4. To genotype all clinical isolates using whole genome sequencing for comparative
genomics.
5. To dissect the natural immune response in scrub typhus, using antigen-specific cellular
immune and antibody studies, and cytokine profiling
Phase:
Phase 4
Details
Lead Sponsor:
University of Oxford
Collaborators:
Chiangrai Prachanukroh Hospital Shoklo Malaria Research Unit