Evaluation of a nitric oxide generating dressing (EDX110) to improve management of Buruli ulcer disease

Treatment of Buruli ulcer disease caused by Mycobacterium ulcerans with antibiotics, rifampicin with clarithromycin given daily for 8 weeks has transformed the management of the disease. However, the rate of healing is highly variable even in patients with seemingly similar lesions. Preliminary evidence from studies in Ghana suggest that factors contributing to variability in healing rate include the initial bacterial load and/or development of paradoxical reactions. One approach to solving this problem would be to enhance killing of M. ulcerans. The antibiotics used as first line therapy were chosen for their bactericidal potency in a mouse model of M. ulcerans infection and it is unlikely that these can be improved upon particularly given the increasing global threat of antimicrobial resistance. We therefore propose an alternative approach, using concurrent treatment with a novel Nitric oxide-generating wound dressing and the antibiotics to enhance healing.

The primary objective is:

• To compare healing, as measured by percentage area reduction, of EDX110 dressing with oral rifampicin and clarithromycin versus ‘Usual Care’ with routine Vaseline gauze dressing and oral rifampicin and clarithromycin.

Secondary objectives include:

• A comparison of the number of complete healers and the recurrence rate in EDX 110 dressing and Vaseline gauze dressing groups.
• A comparison of rate of killing of ulcerans in EDX 110 dressing and Vaseline gauze dressing groups.
• Effect of treatment on the immune profiles of stimulated blood cells for biomarkers of healing
• A comparison of the tolerability of the two dressings.
• Training/ Mentoring of a cadre of Junior Scientists (PhD/Master students/Post doc/Clinical scientists)
• Training of village volunteers in the use and application of the dressing materials

Study design

The study has been designed as a prospective randomized open-blinded end-point (PROBE) study of either rifampicin 10mg/kg and clarithromycin 15mg/kg daily AND Nitric oxide-generating gel dressing (EDX 110) applied on alternate days to the wound or rifampicin 10mg/kg and clarithromycin 15mg/kg daily AND Vaseline gauze dressings applied daily to the wound representing current standard of care. This will be conducted at the KCCR, Ghana and Agogo Presbyterian Hospital, Tepa and Dunkwa Government Hospitals all in Ghana.

Expected Impact

If treatment with topical Nitric oxide combined with oral antibiotics causes more rapid killing of M. ulcerans and enhances healing, treatment will be shortened and made more convenient for patients. This will improve the delivery of treatment. The study will likely produce high impact scientific papers. There will be a significant impact on the pool of trained junior scientists.

The trial has been registered with the Pan African Clinical Trial Registry with identification number PACTR201812819039144. (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=5795) (www.pactr.org).