Oral doxycycline versus oral azithromycin in the treatment of Scrub and Murine Typhus in Laos

ISRCTN	ISRCTN47812566
DOI	https://doi.org/10.1186/ISRCTN47812566
Protocol serial number	066828, 106698/Z/14/Z
Sponsor	University of Oxford (UK)
Funder	Wellcome Trust (grant ref: 066828)

Submission date: 07/12/2005
Registration date: 07/12/2005
Last edited: 23/09/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Paul Newton
Scientific

Microbiology laboratory
Ministry of Health
Mahosot Hospital
Mahosot Road
Vientiane
-
Lao People's Democratic Republic

Phone	+856 (0)21 250752
Email	paul@tropmedres.ac

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	An open, randomised clinical trial of three days oral doxycycline versus seven days oral doxycycline versus three days oral azithromycin in the treatment of Scrub and Murine Typhus
Study acronym	MUT and SUT
Study objectives	That fever clearance times and the frequencies of relapse and treatment failure do not differ between three days oral doxycycline versus seven days oral doxycycline versus three days oral azithromycin in the treatment of scrub and murine typhus.
Ethics approval(s)	1. Oxford Tropical Ethics Committee (OXTREC), 27/03/2003, ref: OXTREC 003-03 2. Faculty of Medical Sciences, Vientiane, Laos Ethical Committee, 03/06/2003, ref: FMS 3-6-2003
Health condition(s) or problem(s) studied	Scrub typhus, murine typhus
Intervention	An open, randomised comparative trial of three days oral doxycycline versus seven days oral doxycycline versus three days oral azithromycin. Added 02/02/2009: Each of the two diseases have the same three treatment arms: 1. Oral doxycycline 100 mg every 12 hours for 7 days (after a 200 mg loading dose) 2. Doxycycline 100 mg every 12 hours for 3 days (after a 200 mg loading dose) 3. Oral azithromycin 500 mg on day 1 and then 250 mg every 24 hours for 2 more days Follow up is for one year.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Doxycycline, azithromycin
Primary outcome measure(s)	Current information as of 02/02/2009: Fever clearance time and area under the fever-time curve during inpatient stay. Initial information at time of registration: 1. Fever clearance times 2. Frequencies of treatment failure 3. Frequencies of relapse
Key secondary outcome measure(s)	Added as of 02/02/2009: 1. Treatment failure frequency 2. Relapse frequency
Completion date	31/12/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	426
Key inclusion criteria	Current information as of 02/02/2009: 1. Adult (greater than 15 years) non-pregnant patients with suspected typhus. Suspected typhus will be defined as undifferentiated fever (aural temperature greater than 37.5°C), with or without an eschar, with a positive scrub typhus Lateral Flow IgM result or a murine typhus IgM Dip-S-Ticks result 2. Written informed consent to the study 3. Able to stay in hospital for the duration of the treatment (up to 7 days) and high likelihood of completing at least 4 weeks follow up 4. Able to take oral medication 5. A negative urinary pregnancy test for all women of child bearing age 6. None of the exclusion criteria Initial information at time of registration: 1. Adult (more than or equal to 15 years, either sex) non-pregnant patients with suspected typhus, with a positive scrub typhus Lateral Flow result or a murine typhus Dip-S-Ticks result 2. Written informed consent 3. Able to stay in hospital for the duration of the treatment 4. High likelihood of completing at least four weeks follow up 5. Able to take oral medication 6. A negative urinary pregnancy test for all women of childbearing age 7. None of the exclusion criteria
Key exclusion criteria	Current information as of 02/02/2009: 1. Known hypersensitivity to tetracycline, doxycycline or azithromycin 2. Administration of chloramphenicol, doxycycline, tetracycline, fluoroquinolones or azithromycin during the preceeding week 3. Pregnancy or breastfeeding 4. Contraindications to doxycycline: severe hepatic impairment, known systemic lupus erythematosus (SLE) 5. Contraindications to azithromycin: severe hepatic impairment 6. Severe typhus defined as: 6.1. Reduced level of consciousness 6.2. Clinical jaundice 6.3. Shock (blood pressure [BP] systolic less than 80 mmHg) 6.4. Vomiting sufficient to disallow the use of oral medication 6.5. Clinical or radiological evidence for lung involvement 6.6. Clinical evidence for meningitis/encephalitis or the need for a lumbar puncture (LP) 6.7. Any other syndrome which in the opinion of the admitting doctor constitutes severe typhus (reason must be stated) Initial information at time of registration: 1. Known hypersensitivity to tetracycline, doxycycline or azithromycin 2. Administration of chloramphenicol, doxycycline, tetracycline, fluoroquinolones or azithromycin during the preceeding week 3. Pregnancy or breast feeding 4. Contraindications to doxycycline or azithromycin and severe typhus
Date of first enrolment	04/08/2003
Date of final enrolment	31/12/2009

Locations

Countries of recruitment

Lao People's Democratic Republic

Study participating centre

Mahosot Hospital

Vientiane
-
Lao People's Democratic Republic

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	15/02/2019		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

23/09/2020: Internal review.
19/07/2018: Publication reference added.
02/02/2009: This record was extensively updated, all updates can be found under the relevant field with the above update date. Please also note that the overall trial end date was changed from 31/12/2008 to 31/12/2009.
13/02/2007: The overall trial end date was changed from 31/12/2006 to 31/12/2008.
08/06/2005: Trial details submitted to the Wellcome Trust.