Buruli-RifDACC: Evaluation of the efficacy and cost-effectiveness of high-dose versus standard-dose rifampicin on outcomes in Mycobacteriumulcerans disease, a protocol for a randomised controlled trial in Ghana

NIHR Open Res. 2023 Feb 24:2:59. doi: 10.3310/nihropenres.13332.2. eCollection 2022.

Abstract

Background: Buruli ulcer (BU) can lead to disfiguring ulcers and permanent disability. The 2030 World Health Organization (WHO) road map for Neglected Tropical Diseases (NTDs) calls for major scaling up in diagnosis and management to eliminate disability due to the disease. Current treatment for BU is with daily oral rifampicin (10mg/kg dose) and clarithromycin (15mg/kg dose) for eight weeks, combined with standard gauze wound dressings. Dialkylcarbamoyl chloride (DACC)-coated dressings have been shown to irreversibly bind bacteria on wound surfaces resulting in their removal when dressings are changed. This trial aims to determine whether combining a high-dose oral rifampicin regimen with DACC dressings can improve the rate of wound healing relative to standard-dose oral rifampicin combined with DACC dressings.

Methods: This is an individual, multi-centre Phase 3 randomised controlled trial, which will be conducted in three clinical sites in Ghana. The primary outcome measure will be the mean time to clearance of viable mycobacteria. Cost and health-related quality of life data will be collected, and a cost-effectiveness analysis will be performed.

Discussion: The findings from this trial could lead to a change in how BU is treated. A shorter but more efficacious regimen would lead to improved treatment outcomes and potentially substantial financial and economic savings.

Trial registration: Pan African Clinical Trials Repository (registration number; PACTR202011867644311). Registered on 30 th November 2020.

Keywords: Buruli ulcer; DACC; High Dose Rifampicin; Randomised Controlled Trial; cost-effectiveness.

Plain language summary

Buruli ulcer (BU), caused by Mycobacterium ulcerans, manifests clinically as a wound or swelling. There are several approaches for managing this condition. One is the availability of two antibiotics, usually rifampicin in combination with clarithromycin, that can be used to treat the disease. Rifampicin is thought to be the most important of these two drugs. Scientists have found out that a higher dose of rifampicin is safe and may help improve healing outcome and shorten the duration of treatment. Individuals with BU wounds also go through wound dressing procedures at their hospitals and health centres. Commonly, wounds are dressed using Vaseline gauze and bandages. However, it has been observed that some affected individuals heal faster than others even with the antibiotic treatment. Some still have living organisms in their wounds many weeks after the antibiotic treatment. There is a new dressing material called DACC which is believed to permanently bind bacteria on the wound surface leading to their removal when the dressings are changed. This may be a good way to treat and prevent infection without the use of more drugs. This study aims to determine whether combining a high-dose oral rifampicin regimen with DACC dressings can improve the rate of wound healing relative to standard-dose oral rifampicin combined with DACC dressings. Furthermore, cost and health-related quality of life data will be collected and a cost-effectiveness analysis will be performed. The findings from this trial could lead to a change in how BU is treated. A shorter but more efficacious regimen would lead to improved treatment outcomes and potentially substantial financial and economic savings.

Grants and funding

This project is funded by the National Institute for Health and Care Research (NIHR) under its Research and Innovation for Global Health Transformation (RIGHT) Programme [Grant Reference Number NIHR200125]. The views expressed are those of the author(s) and not necessarily those of the NIHR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.