Condition category
Infections and Infestations
Date applied
23/11/2005
Date assigned
23/11/2005
Last edited
19/06/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Ploenchan Chetchotsakd

ORCID ID

Contact details

Khon Kaen University
Department of Medicine
Faculty of Medicine
Srinagarind Hospital
Mitrapharp Highways
Khon Kaen
40002
Thailand
+66 (0)4 3363168
ploencha@kku.ac.th

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

077166

Study information

Scientific title

A comparison of doxycycline plus trimethoprim-sulphamethoxazole versus trimethoprim-sulphamethoxazole as maintenance therapy for melioidosis

Acronym

MERTH

Study hypothesis

To evaluate the efficacy, effectiveness and compliance of Trimethoprim-Sulphamethoxazole (TMP-SMX) compared with doxycycline, Trimethoprim (TMP), and Sulphamethoxazole (SMX) in the oral maintenance phase treatment of melioidosis.

Ethics approval

1. The Ethical Review Committee for Research in Human Subjects, Ministry of Public Health, Thailand (IRB00001629), 27/07/2005, ref: 67/2548
2. The Khon Kaen University Ethics Committee (IRB00001189), 20/05/2005, ref: HE7471005
3. The Oxford Tropical Research Ethics Committee (OXTREC), 04/11/2005, ref: 021-05

Study design

Placebo-controlled randomised multicentre study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Melioidosis

Intervention

The patients will be randomised into two groups, and the randomisation will be performed in advance by blocks of ten. Pre-prepared treatment-containing packs will be labelled with the consecutive study numbers. The study drugs include either of the combinations below:

1. Three drugs:
a. Co-trimoxazole (10 mg TMP and 50 mg SMX/kg/day): three adult tablets (80 mg TMP/tab), twice daily. The dose of co-trimoxazole will be reduced to two tablets, twice daily in case of patients with creatinine clearance less than 30 ml/min or who weigh less than 35 kg, and increased to four tablets, twice daily in case of patients who weigh more than 65 kg.
b. Doxycycline (4 mg/kg/day): one tablet twice daily.

2. Two drugs:
a. Co-trimoxazole (10 mg TMP and 50 mg SMX/kg/day): three adult tablets (80 mg TMP/tab), twice daily. The dose of co-trimoxazole will be reduced to two tablets, twice daily in case of patients with creatinine clearance less than 30 ml/min or who weigh less than 35 kg, and increased to four tablets, twice daily in case of patients who weigh more than 65 kg.
b. Placebo (identical tablet as doxycycline): one tablet twice daily.

Intervention type

Drug

Phase

Not Applicable

Drug names

Co-trimoxazole (Trimethoprim and sulphamethoxazole), doxycycline

Primary outcome measures

1. Mortality
2. Recurrent disease: this is defined as clinical features of melioidosis after initial improvement, in association with cultures from any site positive for Burkholderia pseudomallei. This can be any time point during or after stopping antibiotic treatment.

Secondary outcome measures

1. Clinical recurrence: recurrent clinical features of melioidosis treated as such but not confirmed by positive culture
2. Treatment failure: clinical decision to change treatment according to inadequate response to therapy
3. Adverse drug reactions, including drug allergy
4. Drug compliance: based on interview and pill counting

Overall trial start date

26/10/2005

Overall trial end date

31/10/2009

Reason abandoned

Eligibility

Participant inclusion criteria

1. Culture-confirmed melioidosis
2. Satisfactory completion of intravenous therapy and able to take oral medication
3. Patients with mild localised disease who are not considered to require intravenous treatment by their primary physician are eligible if they agree to return for follow up
5. Aged over 14 years, either sex
6. High likelihood of completing at least six months follow up
7. Willingness to participate in the study and written, informed consent obtained from the patient

Participant type

Patient

Age group

Mixed

Gender

Both

Target number of participants

600

Participant exclusion criteria

1. Pregnancy or breast feeding
2. Contraindications to doxycycline: severe hepatic impairment (aspartate aminotransferase [AST], alanine aminotransferase [ALT] more than or equal to five times of upper limit of normal)
3. Contraindications to TMP-SMX: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, renal impairment (creatinine clearance less than 15 ml/min)
4. History of hypersensitivity to doxycycline, TMP or SMX
5. Infecting isolate is resistant to TMP-SMX by E-test
6. Relapse melioidosis with disease free interval of less than two years

Recruitment start date

26/10/2005

Recruitment end date

31/10/2008

Locations

Countries of recruitment

Thailand

Trial participating centre

Khon Kaen University
Khon Kaen
40002
Thailand

Sponsor information

Organisation

Khon Kaen University (Thailand)

Sponsor details

Department of Medicine
Faculty of Medicine
Srinagarind Hospital
Mitrapharp Highways
Khon Kaen
40002
Thailand

Sponsor type

University/education

Website

http://www.kku.ac.th/eng/index.html

Funders

Funder type

Charity

Funder name

Wellcome Trust (UK) (grant ref: 077166)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

international

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/24284287

Publication citations

  1. Results

    Chetchotisakd P, Chierakul W, Chaowagul W, Anunnatsiri S, Phimda K, Mootsikapun P, Chaisuksant S, Pilaikul J, Thinkhamrop B, Phiphitaporn S, Susaengrat W, Toondee C, Wongrattanacheewin S, Wuthiekanun V, Chantratita N, Thaipadungpanit J, Day NP, Limmathurotsakul D, Peacock SJ, Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): a multicentre, double-blind, non-inferiority, randomised controlled trial., Lancet, 2014, 383, 9919, 807-814, doi: 10.1016/S0140-6736(13)61951-0.

Additional files

Editorial Notes