Scrub Typhus Antibiotic Resistance Trial

• Register: ClinicalTrials.gov
• Last refreshed on: 4 April 2022
• Main ID: NCT03083197
• Date of registration: 13/03/2017
• Prospective Registration: Yes
• Primary sponsor: University of Oxford
• Public title: Scrub Typhus Antibiotic Resistance Trial START
• Scientific title: The Scrub Typhus Antibiotic Resistance Trial (START) Comparing Doxycycline and Azithromycin Treatment Modalities in Areas of Reported Antimicrobial Resistance for Scrub Typhus
• Date of first enrolment: October 15, 2017
• Target sample size: 177
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT03083197
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

Thailand

Contacts

• Name: Assoc. Prof. Daniel Paris
• Affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand

• Name: Assoc. Prof. Daniel Paris

Key inclusion & exclusion criteria

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 immunosuppressants (e.g. steroids,
chemotherapy, TNF-inhibitors and related agents)

- Patients with severe disease whom the clinical team feel their condition necessitates
the need for additional scrub typhus treatment beyond the allocated antibiotic
treatment assigned at randomization (e.g. IV chloramphenicol and/or PO/NG rifampicin)



Age minimum: 15 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Scrub Typhus

Intervention(s)

Drug: Doxycycline 3 days

Drug: Doxycycline 7 days

Drug: Azithromycin 3 days

Primary Outcome(s)

Fever clearance time (FCT) [Time Frame: at least 24 hours]

Secondary Outcome(s)

Occurrence of severe disease or treatment failure/relapse [Time Frame: 8 Weeks]

Presence of in vitro antimicrobial resistance [Time Frame: 8 Weeks]

Resolution of bacteraemia in relation to Drug plasma level [Time Frame: 8 Weeks]

Antigen-specific positive cellular and humoral immune responses [Time Frame: 8 Weeks]

Genotyping of clinical Orientia tsutsugamushi isolates (56kDa gene +/- whole genome sequencing) [Time Frame: 2 years]

Secondary ID(s)

START

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Chiangrai Prachanukroh Hospital

Shoklo Malaria Research Unit