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

NCT06695143 | Not Yet Recruiting Phase 3

• 1 other identifier: AIM-CL
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 2

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.

Conditions

Leishmaniasis, Cutaneous

Keywords

Cutaneous Leishmania; Complicated cutaneous leishmania

Outcome Measures

Primary Outcomes (1)

• Improvement of index lesion at EoT

  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.

  28 days

Secondary Outcomes (12)

• Arm 1 superiority to arm 3 - index lesion

  42 days

• Arm 1 superiority to arm 3 - lesions eligible for treatment

  42 days

• Proportion of participants that reach substiantial improvement - arm 1 vs arm 2

  42 days

• Proportion of participants that reach substiantial improvement - arm 2 vs arm 3

  42 days

• Cycles needed for final cure

  180 days

Study Arms (3)

Treatment - SoC + fusidic acid 2% cream

EXPERIMENTAL

4 weeks SSG (SoC) with 2 weeks twice daily topical application of fusidic acid 2% cream

Drug: Fusidic Acid

Vehicle - SoC + vehicle cream

ACTIVE COMPARATOR

4 weeks SSG (SoC) with 2 weeks twice daily topical application of vehicle cream

Other: Vehicle cream

Control - SoC

NO INTERVENTION

4 weeks SSG (SoC) only

Interventions

Fusidic Acid DRUG

Fusidic acid 2% cream

Treatment - SoC + fusidic acid 2% cream

Vehicle cream OTHER

Cetomacrogol cream

Vehicle - SoC + vehicle cream

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

• Clinical diagnosis of CL
• Need for systemic treatment (1 or more of these criteria)
• Mucosal involvement of lesion or at risk for mucosal involvement (\< 1 cm from the nose, eyes and vermillion border of the lips)
• Lesion size \>4 cm
• \>4 lesions
• Lesions on joints or fingers
• Lesions previously not responding to local treatment
• Lesions unsuitable for local treatment (e.g., eyelids)
• Lesions with signs of dissemination (satellite lesions, nodular lymphangitis, sporotrichoid pattern)
• Age \> 4 (minimum age to receive systemic treatment with SSG)
• At least one lesion eligible for treatment\* (meeting all criteria below)
• lesion with surface change, including ulcerated, crusted and scaly lesions
• distinguishable from other lesions (minimum 0.5 cm apart)
• no mucosal involvement against which a topical agent would likely not be effective (e.g., lesions that are located too deep within the nasal passages or on the inner lip, where proper application is challenging and the ointment may be easily removed or not adequately absorbed)
• Willing and able to provide informed consent. For participants under the age of 18, parental or caregiver consent is required. Additionally, assent must be obtained from adolescents aged 12 to 17

Sponsors & Collaborators

• Institute of Tropical Medicine, Belgium: lead
• Armauer Hansen Research Institute (AHRI), Ethiopia: collaborator
• Arba Minch University: collaborator

Study Sites (2)

Arba Minch General Hospital

Arba Minch, Ethiopia

Location

Chencha Primary Hospital

Chencha, Ethiopia

Location

MeSH Terms

Conditions

Leishmaniasis, Cutaneous

Interventions

Fusidic Acid

Condition Hierarchy (Ancestors)

Leishmaniasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Vector Borne Diseases; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cholestadienols; Cholestadienes; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Membrane Lipids; Lipids

Study Officials

• Johan Van Griensven, Prof

  Head of department of clinical sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gaetan Van Aelst

CONTACT

+32(0)32476778; gvanaelst@itg.be

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2024
• First Posted: November 19, 2024
• Study Start: April 1, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: November 19, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

ET (2)