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
The funder is USAMRMC - MIDRP and Grant No. DHP-Award D6.7\_15\_C2\_I\_15\_J9\_1317
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
177
loading dose 200mg PO, then 100mg PO every 12 hours for 7 days
loading dose 200mg PO, then 100mg PO every 12 hours for 3 days
loading dose 1000mg PO on day 1, then 500mg PO every 24 hours on days 2 and 3
Shoklo-Malaria Research Unit (SMRU)
Mae Sot, Changwat Tak, Thailand
NOT_YET_RECRUITINGChiangrai Prachanukroh Hospital
Chiang Rai, Thailand
RECRUITINGFever clearance time (FCT)
Based on the time from first dose of antibiotic treatment to when the tympanic temperature first falls ≤37.5°C and remains ≤37.5°C for at least 24 hours, outside of the influence of paracetamol.
Time frame: at least 24 hours
Resolution of bacteraemia in relation to Drug plasma level
Time frame: 8 Weeks
Occurrence of severe disease or treatment failure/relapse
Time frame: 8 Weeks
Presence of in vitro antimicrobial resistance
(Minimum inhibitory concentrations (MIC) over susceptibility cut off)
Time frame: 8 Weeks
Genotyping of clinical Orientia tsutsugamushi isolates (56kDa gene +/- whole genome sequencing)
Genotyping of clinical OT isolates will be performed on patient samples that are PCR positive (approximately 50-60%) and/or culture positive (approximately 30%). Extracted DNA will be sent for 56kDa gene sequencing +/- whole genome sequencing, revealing the clinically important strains and allowing for comparative analysis with disease severity and patient outcomes.
Time frame: 2 years
Antigen-specific positive cellular and humoral immune responses
Time frame: 8 Weeks
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