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:

  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 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