Co-trimoxazole as Maintenance Therapy for Melioidosis

A Comparison Between 12 vs. 20 Weeks of Co-trimoxazole as Maintenance Therapy for Melioidosis

This is a randomised, open-labelled, controlled trial to compare the efficacy and effectiveness on relapse-free rate of 12-week versus 20-week oral eradication treatment of melioidosis. The study population includes 800 patients with culture-confirmed melioidosis whom 12 weeks of oral eradication therapy have been completed with or without intravenous intensive antibiotics. Patients will be randomised to either stop the eradication treatment or continue current oral treatment for 8 more weeks. The study aim to optimise the regimen used to treat melioidosis for better compliance and reducing unnecessary use of antibiotics.

Study Overview

• Status: Completed
• Conditions: Melioidosis
• Intervention / Treatment: Drug: Co-trimoxazole 12; Drug: Co-trimoxazole 20

Detailed Description

Planed interim analysis will be conducted when the patient enrollment reaches 600 cases for evaluating safety and futility of the study.

• Study Type: Interventional
• Enrollment (Actual): 667
• Phase: Phase 4

Contacts and Locations

Study Locations

• Thailand
  • Khon Kaen, Thailand
    • Khon Kaen Univerisity

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age > 15 years
2. Culture-confirmed melioidosis
3. Currently on oral co-trimoxazole for 12(+2) weeks without any clinical evidence of active melioidosis
4. High likelihood of completing at least 6 months follow up
5. Willingness to participate in the study and written, informed consent obtained from the patient

Exclusion Criteria:

1. Pregnancy or breast feeding
2. Contraindications to TMP-SMX: G6PD, severe adverse reactions grade 3-4 occurring during first 12 weeks of treatment
3. Relapse melioidosis with at least 2 year symptom free period from last episode

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Co-trimoxazole 12; Receive treatment with co-trimoxazole for 12 weeks.	Drug: Co-trimoxazole 12; Receive treatment with co-trimoxazole for 12 weeks.
Experimental: Co-trimoxazole 20; Receive treatment with co-trimoxazole for 20 weeks.	Drug: Co-trimoxazole 20; Receive treatment with co-trimoxazole for 20 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year non relapse rate	This is defined as clinical features of melioidosis after initial improvement, in association with cultures from any site positive for Burkhoderia pseudomallei. This can be any time point during or after stopping antibiotic treatment.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality		1 year
Clinical Recurrence	Recurrent clinical features of melioidosis treated as such but not confirmed by positive culture.	1 year
Treatment failure	Clinical decision to change treatment according to inadequate response to therapy.	9 weeks
Adverse Drug Reactions	Adverse events that are caused by the drug including drug allergy.	9 weeks
Drug compliance	This will be done by interviewing and pill counting.	12 or 20 weeks

Collaborators and Investigators

• Sponsor: Khon Kaen University
• Investigators: Principal Investigator: Siriluck Anunnatsiri, MD, Khon Kaen Univerisity

Publications and helpful links

General Publications

• Anunnatsiri S, Chaowagul W, Teparrukkul P, Chetchotisakd P, Tanwisaid K, Khemla S, Narenpitak S, Pattarapongsin M, Kongsawasd W, Pisuttimarn P, Thipmontree W, Mootsikapun P, Chaisuksant S, Chierakul W, Day NPJ, Limmathurotsakul D. A Comparison Between 12 Versus 20 Weeks of Trimethoprim-sulfamethoxazole as Oral Eradication Treatment for Melioidosis: An Open-label, Pragmatic, Multicenter, Non-inferiority, Randomized Controlled Trial. Clin Infect Dis. 2021 Dec 6;73(11):e3627-e3633. doi: 10.1093/cid/ciaa1084.

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): June 21, 2019
• Study Completion (Actual): June 21, 2019

Study Registration Dates

• First Submitted: August 18, 2011
• First Submitted That Met QC Criteria: August 18, 2011
• First Posted (Estimate): August 19, 2011

Study Record Updates

• Last Update Posted (Actual): September 3, 2020
• Last Update Submitted That Met QC Criteria: September 1, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Relapse; Melioidosis; Co-trimoxazole
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Burkholderia Infections; Melioidosis; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anti-Infective Agents, Urinary; Renal Agents; Trimethoprim, Sulfamethoxazole Drug Combination
• Other Study ID Numbers: HE541074; project number 542040 (Other Grant/Funding Number: Khon Kaen University); 106698/B/14/Z (Other Grant/Funding Number: Wellcome Trust)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No