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Antimicrobial Adjuvants to Revert the Imbalance of Skin Microbiota for Improved Outcomes of Complicated Cutaneous Leishmaniasis Treatment in Ethiopia

Phase 3
Not yet recruiting
Conditions
Leishmaniasis, Cutaneous
Interventions
Other: Vehicle cream
Registration Number
NCT06695143
Lead Sponsor
Institute of Tropical Medicine, Belgium
Brief Summary

This clinical trial aims to evaluate the effectiveness of combining the standard treatment for complicated cutaneous leishmaniasis (CL), sodium stibogluconate (SSG), with either topical fusidic acid 2% cream or a vehicle cream without active ingredient. The goal is to assess whether this combination improves treatment outcomes by restoring the balance of the skin microbiome (dysbiosis) in patients with severe CL, a condition common in Ethiopia.

The study will compare three treatment groups:

* Fusidic Acid Group: SSG plus topical fusidic acid for 2 weeks.

* Vehicle Cream Group: SSG plus topical vehicle cream for 2 weeks.

* Control Group: SSG only, with no topical treatment.

The primary objective is to determine if the addition of fusidic acid improves treatment outcomes compared to SSG alone, as measured by substantial improvement in the index lesion at the end of treatment (EoT).

A total of 180 patients will be enrolled at two hospitals in Ethiopia. The trial will run for 24 months, with a focus on understanding how restoring the skin microbiome can improve CL treatment outcomes and potentially provide a low-cost, accessible treatment strategy for CL patients.

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
180
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Treatment - SoC + fusidic acid 2% creamFusidic Acid4 weeks SSG (SoC) with 2 weeks twice daily topical application of fusidic acid 2% cream
Vehicle - SoC + vehicle creamVehicle cream4 weeks SSG (SoC) with 2 weeks twice daily topical application of vehicle cream
Primary Outcome Measures
NameTimeMethod
Improvement of index lesion at EoT28 days

To assess if 4 weeks SoC with 2 weeks application of 2% fusidic acid twice per day (Arm 1, Treatment) is superior to 4 weeks SoC only (Arm 3, Control) for complicated CL patients, in terms of reaching at least substantial improvement\* of the index lesion\*\* at the end of treatment (EoT).

\*Substantial improvement is defined as \>50% flattening and \>50% re-epithelization compared to the baseline assessment. Improvement will be measured for each lesion. At least the index lesion needs to be improved or cured for a patient to be considered substantially improved.

\*\*Index lesion is defined as the largest lesion eligible for treatment.

Secondary Outcome Measures
NameTimeMethod
Cycles needed for final cure180 days

To compare the number of cycles needed to reach final cure per treatment arm

Proportion of cured patients at day 180180 days

To determine the proportion with 95% CI of patients that reach cure without relapsed or worsening at day 180 for the three treatment arms

Arm 1 superiority to arm 3 - index lesion42 days

To assess if Arm 1 is superior to Arm 3, using an ordinal (no improvement, minor improvement, substantial improvement, cure, relapse) and continuous (% re-epithelization/flattening) outcome measures for the index lesion at EoT and D42

Arm 1 superiority to arm 3 - lesions eligible for treatment42 days

To assess if Arm 1 is superior to Arm 3, using binary (at least substantial improvement), ordinal (no improvement, minor improvement, substantial improvement, cure, relapse) and continuous (% re-epithelization/flattening) outcome measures for all lesions eligible for treatment individually and combined at EoT and D42

Proportion of participants that reach substiantial improvement - arm 1 vs arm 242 days

To compare the proportion of patients that reach at least substantial improvement of the index lesion, all lesions combined and individually at EoT and D42 between patients who received SoC with topical 2% fusidic acid (Arm 1, Treatment), and those who received SoC combined with topical vehicle cream (Arm 2, Vehicle)

Proportion of participants that reach substiantial improvement - arm 2 vs arm 342 days

To compare the proportion of patients that reach at least substantial improvement of the index lesion, all lesions combined and individually at EoT and D42 between patients who received SoC combined with topical vehicle cream (Arm 2, Vehicle), and those who received SoC only (Arm 3, Control)

Quality of life - patient reported outcome180 days

To compare change over time of patient-reported outcomes - the dermatological life quality index (DLQI) scores and global assessment - per treatment arm

Safety and acceptability180 days

To assess safety and acceptability of treatment arms

a) Withdrawal from study intervention: proportion and 95% CI of patients withdrawn from intervention, per arm b) Adverse events: number and proportion of patients with adverse events, per arm c) Cumulative incidence of adverse events (AEs) related to the study drug d) Recommendability: acceptability and recommendability score (0-10) given by patients after treatment completion, per arm

Stability microbial diversity180 days

To determine the stability of microbial diversity in the healthy skin over time

Correlation microbial diversity and substantial improvement180 days

To determine whether increase in microbial diversity at EoT compared to D0 is correlated with substantial improvement of the index lesion and all lesions combined at EoT for the three trial arms

Correlation microbial diversity and cure without relapse180 days

To determine whether increase in microbial diversity at M6 compared to D0 is correlated with cure without relapse at M6, for the three trial arms

Increase microbial diversity180 days

To assess the increase in microbial diversity indices within each trial arm at D14, EoT, D42 and M6 compared to D0.

Trial Locations

Locations (2)

Arba Minch General Hospital

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Arba Minch, Ethiopia

Chencha Primary Hospital

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Chencha, Ethiopia

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