Clinical Trial: Scrub Typhus Antibiotic Resistance Trial
Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional
Official Title: The Scrub Typhus Antibiotic Resistance Trial (START) Comparing Doxycycline and Azithromycin Treatment Modalities in Areas of Reported Antimicrobial Resistance for Scrub Typhus
Brief 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:
- 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 profilin
Detailed Summary:
Sponsor: University of Oxford
Current 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.
Original Primary Outcome: Same as current
Current Secondary Outcome:
- 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 ](Minimum inhibitory concentrations (MIC) over susceptibility cut off)
- 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.
- Antigen-specific positive cellular and humoral immune responses [ Time Frame: 8 Weeks ]
Original Secondary Outcome:
- 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 ](Minimum inhibitory concentrations (MIC) over susceptibility cut off)
- Successful genotyping of causative strains [ Time Frame: 8 Weeks ]
- Antigen-specific positive cellular and humoral immune responses [ Time Frame: 8 Weeks ]
Information By: University of Oxford
Dates:
Date Received: March 13, 2017
Date Started: May 15, 2017
Date Completion: May 2019
Last Updated: May 8, 2017
Last Verified: May 2017