The STROGHAT study protocol: An intervention study to evaluate safety, effectiveness and feasibility of treating gambiense HAT seropositive subjects with acoziborole.

Abstract

Background: Coordinated efforts in the control of gambiense human African trypanosomiasis (gHAT) have significantly reduced its endemicity. WHO targets interruption of transmission by 2030. However, challenges remain, including low sensitivity of the current parasitological confirmation tests, leaving a potential human reservoir untreated. Acoziborole, a single-dose oral treatment, effective in both disease stages with a good safety profile, offers the potential of treatment of parasitologically negative gHAT seropositive subjects, which could improve diagnostic sensitivity. The STROGHAT study aims to evaluate whether this approach can lead to elimination of T.b. gambiense from its human reservoir, and to provide further safety data on acoziborole. It also includes a costing analysis and a prospective evaluation of the performance of the screening and diagnostic tests used. Methods: STROGHAT is a one-arm epidemiological study, with a nested phase IIIb, one-arm, open label, non-randomized, multicentre clinical trial. It will be implemented over four years in the endemic region of the Equateur North, in the Democratic Republic of Congo. For the first three years, parasitologically negative gHAT seropositive subjects will be treated with acoziborole, while parasitologically confirmed cases will receive standard of care. Individual follow-up needs and accurate prevalence estimate will be based on immunological and molecular tests performed for all gHAT screening test seropositive subjects at a reference laboratory. In the fourth year, standard procedures will resume, and a prevalence survey will assess whether interruption of transmission has been achieved. Discussion: The manuscript outlines the study background, objectives and methods while discussing its strengths and challenges. If successful, the STROGHAT study will provide critical evidence on the effectiveness, safety and feasibility of the new strategy, and inform future elimination strategies. Clinical trial registration: https://clinicaltrials.gov/study/NCT06356974?term=NCT06356974&rank=1 NCT06356974. Date of registration: April 4, 2024.