- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03083197
Scrub Typhus Antibiotic Resistance Trial (START)
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
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Assoc. Prof. Daniel Paris
- Phone Number: +6622036373
- Email: parigi@tropmedres.ac
Study Contact Backup
- Name: Tri Wangrangsimakul
- Phone Number: +6622036333
- Email: tri@tropmedres.ac
Study Locations
-
-
-
Chiang Rai, Thailand
- Recruiting
- Chiangrai Prachanukroh Hospital
-
Contact:
- Tri Wangrangsimakul, MD
- Email: Tri@tropmedres.ac
-
-
Tak
-
Mae Sot, Tak, Thailand
- Not yet recruiting
- Shoklo-Malaria Research Unit (SMRU)
-
Contact:
- Rose McGready, Prof
- Email: rose@shoklo-unit.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Doxycycline 7 days
loading dose 200mg PO, then 100mg PO every 12 hours for 7 days
|
loading dose 200mg PO, then 100mg PO every 12 hours for 7 days
|
Active Comparator: Doxycycline 3 days
loading dose 200mg PO, then 100mg PO every 12 hours for 3 days
|
loading dose 200mg PO, then 100mg PO every 12 hours for 3 days
|
Active Comparator: Azithromycin 3 days
loading dose 1000mg PO on day 1, then 500mg PO every 24 hours on days 2 and 3
|
loading dose 1000mg PO on day 1, then 500mg PO every 24 hours on days 2 and 3
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
at least 24 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Resolution of bacteraemia in relation to Drug plasma level
Time Frame: 8 Weeks
|
8 Weeks
|
|
Occurrence of severe disease or treatment failure/relapse
Time Frame: 8 Weeks
|
8 Weeks
|
|
Presence of in vitro antimicrobial resistance
Time Frame: 8 Weeks
|
(Minimum inhibitory concentrations (MIC) over susceptibility cut off)
|
8 Weeks
|
Genotyping of clinical Orientia tsutsugamushi isolates (56kDa gene +/- whole genome sequencing)
Time Frame: 2 years
|
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.
|
2 years
|
Antigen-specific positive cellular and humoral immune responses
Time Frame: 8 Weeks
|
8 Weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Assoc. Prof. Daniel Paris, Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Infections
- Vector Borne Diseases
- Gram-Negative Bacterial Infections
- Bacterial Infections
- Bacterial Infections and Mycoses
- Rickettsia Infections
- Rickettsiaceae Infections
- Typhus, Epidemic Louse-Borne
- Scrub Typhus
- Anti-Infective Agents
- Anti-Bacterial Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Doxycycline
- Azithromycin
Other Study ID Numbers
- START
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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