Active — Not RecruitingPhase 4

Scrub Typhus Antibiotic Resistance Trial

Thailand177 participantsStarted 2017-10-15

Plain-language summary

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

Who can participate

Age range15 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Age ≥ 15 years old * Hospitalization with acute undifferentiated fever (temperature \> 37.5°C, tympanic) ≤14 days or patients admitted to hospital with a history of fever ≤ 14 days who subsequently develop fever within 24 hours of admission * Clinically suspected scrub typhus: defined as acute undifferentiated fever with no clear focus of infection and negative malaria blood smear and/or negative malaria RDT. Patients may have one, none, or a combination of other clinical findings such as eschar, rash, lymphadenopathy, headache, myalgia, cough, nausea and abdominal discomfort. * A positive scrub typhus RDT (Scrub Typhus IgM RDT, InBios International, Seattle, WA, USA) and/or positive PCR-based detection of O. tsutsugamushi DNA from the admission blood sample * Written informed consent and/or, written informed assent as required * Able to take oral medication Exclusion Criteria: * Known hypersensitivity to tetracycline, doxycycline or azithromycin * Administration of doxycycline, azithromycin, chloramphenicol, rifampicin, or tetracycline during the preceding 7 days * Pregnancy or breast-feeding * Patients with myasthenia gravis or systemic lupus erythematosus * Patients with an established infection (diagnostic test required) e.g. acute malaria, dengue, leptospirosis, typhoid, Japanese encephalitis etc. * Current TB or TB treatment in ≤ 6 months (contain active antibiotics against Orientia spp.) * Current HAART use for HIV, long term use of immunosuppr…

What they're measuring

Fever clearance time (FCT)

Timeframe: at least 24 hours

Trial details

NCT IDNCT03083197

SponsorUniversity of Oxford

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2026-10-31