Scrub TyphusPhase 4STARTNCT03083197
Scrub Typhus Antibiotic Resistance Trial
A Phase 4 study testing Doxycycline 7 days, Doxycycline 3 days and Azithromycin 3 days in people with Scrub Typhus, run by University of Oxford at 5 sites in Thailand.
Trial 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. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Scrub Typhus
- What is being tested?
- Doxycycline 7 days, Doxycycline 3 days and Azithromycin 3 days
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 177 participants
- Where
- 5 sitesThailand
- Study dates
- 15 Oct 2017to Oct 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Thailand5 sites
Chiangrai Prachanukroh Hospital
Chiang Rai
Mae Chan District Hospital
Chiang Rai
Mae Fah Luang District Hospital
Chiang Rai
Mae Suai District Hospital
Chiang Rai
Shoklo-Malaria Research Unit (SMRU)
Mae Sot, Changwat Tak
About this study
Official title: The Scrub Typhus Antibiotic Resistance Trial (START) Comparing Doxycycline and Azithromycin Treatment Modalities in Areas of Reported Antimicrobial Resistance for Scrub Typhus
Study type: Randomized Control Treatment Trial
Study population: Male and female patients with ≥15 years of age and acute scrub typhus
Read more
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:
- To perform pharmacokinetic/pharmacodynamics (PK/PD) characterization of the therapeutic responses for doxycycline and azithromycin, incl. serial bacterial load measurements.
- To define clinical, bacterial, pathophysiological and pharmacological factors associated with disease severity, fever-clearance times (FCT), treatment failures and relapse/re-infection.
- To determine the minimum inhibitory concentrations (MIC) of clinical Orientia tsutsugamushi isolates to doxycycline, azithromycin and chloramphenicol, using in vitro growth-inhibition assays
- To genotype all clinical isolates using whole genome sequencing for comparative genomics.
- To dissect the natural immune response in scrub typhus, using antigen-specific cellular immune and antibody studies, and cytokine profiling
Read the detailed description
The funder is USAMRMC - MIDRP and Grant No. DHP-Award D6.7_15_C2_I_15_J9_1317
- Conditions
- Scrub Typhus
- Being tested
- Doxycycline 7 days, Doxycycline 3 days, Azithromycin 3 days
- Keywords
- Scrub Typhus, Antibiotic Resistance
- Medical subject headings
- Scrub Typhus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Doxycycline 7 daysDrug
loading dose 200mg PO, then 100mg PO every 12 hours for 7 days
Doxycycline 3 daysDrug
loading dose 200mg PO, then 100mg PO every 12 hours for 3 days
Azithromycin 3 daysDrug
loading dose 1000mg PO on day 1, then 500mg PO every 24 hours on days 2 and 3
| Study group | Role | What they receive |
|---|---|---|
| Doxycycline 7 days | Active comparator | loading dose 200mg PO, then 100mg PO every 12 hours for 7 days Receives: Drug: Doxycycline 7 days |
| Doxycycline 3 days | Active comparator | loading dose 200mg PO, then 100mg PO every 12 hours for 3 days Receives: Drug: Doxycycline 3 days |
| Azithromycin 3 days | Active comparator | loading dose 1000mg PO on day 1, then 500mg PO every 24 hours on days 2 and 3 Receives: Drug: Azithromycin 3 days |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fever 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.
Measured: at least 24 hours
Secondary outcomes (5)
Resolution of bacteraemia in relation to Drug plasma level
Measured: 8 Weeks
Occurrence of severe disease or treatment failure/relapse
Measured: 8 Weeks
Presence of in vitro antimicrobial resistance
(Minimum inhibitory concentrations (MIC) over susceptibility cut off)
Measured: 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.
Measured: 2 years
Antigen-specific positive cellular and humoral immune responses
Measured: 8 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2017
- Study start15 Oct 2017
- Primary completion31 Oct 2026 (estimated)
- Study completionOct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Scrub TyphusStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 177 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Shoklo Malaria Research Unit, Chiangrai Prachanukroh Hospital, Mae Suai District Hospital, Mae Chan District Hospital, Mae Fa Luang District Hospital
- Responsible party
- Sponsor
- Investigators
- Assoc. Prof. Daniel Paris, Principal investigator, Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03083197
- Sponsor's protocol ID
- START
- Acronym
- START
- Status last verified
- Apr 2026
- First submitted
- 13 Mar 2017
- Last updated
- 28 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Scrub Typhus Antibiotic Resistance Trial (START) Comparing Doxycycline and Azithromycin Treatment Modalities in Areas of Reported Antimicrobial Resistance for Scrub Typhus
- ClinicalTrials.gov ID
- NCT03083197
- Acronym / sponsor ID
- START / START
- Conditions
- Scrub Typhus
- Keywords
- Scrub Typhus, Antibiotic Resistance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 177 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Shoklo Malaria Research Unit, Chiangrai Prachanukroh Hospital, Mae Suai District Hospital, Mae Chan District Hospital, Mae Fa Luang District Hospital
- Study start
- 15 Oct 2017 (actual)
- Primary completion
- 31 Oct 2026 (estimated)
- Study completion
- Oct 2028 (estimated)
- First posted
- 17 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To perform pharmacokinetic/pharmacodynamics (PK/PD) characterization of the therapeutic responses for doxycycline and azithromycin, incl. serial bacterial load measurements.
- To define clinical, bacterial, pathophysiological and pharmacological factors associated with disease severity, fever-clearance times (FCT), treatment failures and relapse/re-infection.
- To determine the minimum inhibitory concentrations (MIC) of clinical Orientia tsutsugamushi isolates to doxycycline, azithromycin and chloramphenicol, using in vitro growth-inhibition assays
- To genotype all clinical isolates using whole genome sequencing for comparative genomics.
- To dissect the natural immune response in scrub typhus, using antigen-specific cellular immune and antibody studies, and cytokine profiling
Detailed description
The funder is USAMRMC - MIDRP and Grant No. DHP-Award D6.7_15_C2_I_15_J9_1317
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Doxycycline 7 days | Active comparator | Drug: Doxycycline 7 daysloading dose 200mg PO, then 100mg PO every 12 hours for 7 days |
| Doxycycline 3 days | Active comparator | Drug: Doxycycline 3 daysloading dose 200mg PO, then 100mg PO every 12 hours for 3 days |
| Azithromycin 3 days | Active comparator | Drug: Azithromycin 3 daysloading dose 1000mg PO on day 1, then 500mg PO every 24 hours on days 2 and 3 |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Doxycycline 7 daysloading dose 200mg PO, then 100mg PO every 12 hours for 7 days | Drug | Doxycycline 7 days |
| Doxycycline 3 daysloading dose 200mg PO, then 100mg PO every 12 hours for 3 days | Drug | Doxycycline 3 days |
| Azithromycin 3 daysloading dose 1000mg PO on day 1, then 500mg PO every 24 hours on days 2 and 3 | Drug | Azithromycin 3 days |
Primary outcome
Fever clearance time (FCT)
Time frame: at least 24 hours
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.
5 secondary outcomes
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
Time frame: 8 Weeks
Genotyping of clinical Orientia tsutsugamushi isolates (56kDa gene +/- whole genome sequencing)
Time frame: 2 years
Antigen-specific positive cellular and humoral immune responses
Time frame: 8 Weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Scrub Typhus
RecruitingPhase 2/3
Rickettsia Clearance Study
Infectious Disease, Therapeutics
Active, not recruitingObservational study
Scrub Typhus Infection Induced Cardiovascular Disease
Scrub Typhus, Cardiovascular Complication
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Assoc. Prof. Daniel Paris principal investigator
Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Doxycycline 7 days, Doxycycline 3 days and Azithromycin 3 days in people with Scrub Typhus, run by University of Oxford at 5 sites in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 28 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fever clearance time (FCT) (time frame: at least 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2026.