Antimicrobial Adjuvants to Revert the Imbalance of Skin Microbiota for Improved Outcomes of Complicated Cutaneous Leishmaniasis Treatment in Ethiopia (AIM-CL)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Leishmaniasis, Cutaneous
• Intervention / Treatment: Drug: Fusidic Acid; Other: Vehicle cream

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Gaetan Van Aelst; Phone Number: +32(0)32476778; Email: gvanaelst@itg.be

Study Locations

• Ethiopia
  • Arba Minch, Ethiopia
    • Arba Minch General Hospital
    • Contact: Tamiru Degaga, Dr.; Phone Number: +251 (0)9 117 047 67; Email: drtamshib@gmail.com
  • Chencha, Ethiopia
    • Chencha Primary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Clinically suspected complicated CL patients visiting the study site meeting the following inclusion criteria and none of the exclusion criteria:

Inclusion:

• 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
• Willing to be hospitalized for 4 weeks

Exclusion:

• DCL patients
• Only lesions not eligible for treatment*
• Currently on treatment or having received non-traditional antileishmanial treatment (cryotherapy, thermotherapy, sodium stibogluconate, meglumine antimoniate, paromomycin, pentamidine, AmBisome, miltefosine, non-liposomal amphotericin B) in the past 1 month
• Currently on or having received topical antibiotic treatment for CL lesion(s) in the past 1 month
• Currently on or having received systemic antibiotic treatment in general in the past 1 month
• Currently in need for systemic antibiotics
• Pregnant (positive pregnancy test at D0) or breastfeeding

• Abnormal lab values

  • Hemoglobin < 5.0g/100mL
  • Platelets < 50 x 10^9/L
  • White blood count < 1 x 10^9/L
  • ASAT/ALAT > 3x upper normal range
  • Creatinine above the normal limit
• Prolonged QTc interval or arrythmia on ECG or history of arrythmias
• Known serious kidney or liver disease
• Known allergies to one of the study components/medications
• Serious adverse reaction to a previous SSG dose *If a patient has multiple lesions, of which some are eligible for treatment and others are not, the patient can still be involved in the study. Only the eligible lesions will be subjected to treatment and outcome assessment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment - SoC + fusidic acid 2% cream; 4 weeks SSG (SoC) with 2 weeks twice daily topical application of fusidic acid 2% cream	Drug: Fusidic Acid; Fusidic acid 2% cream
Active Comparator: Vehicle - SoC + vehicle cream; 4 weeks SSG (SoC) with 2 weeks twice daily topical application of vehicle cream	Other: Vehicle cream; Cetomacrogol cream
No Intervention: Control - SoC; 4 weeks SSG (SoC) only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arm 1 superiority to arm 3 - index lesion	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	42 days
Arm 1 superiority to arm 3 - lesions eligible for treatment	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	42 days
Proportion of participants that reach substiantial improvement - arm 1 vs arm 2	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)	42 days
Proportion of participants that reach substiantial improvement - arm 2 vs arm 3	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)	42 days
Cycles needed for final cure	To compare the number of cycles needed to reach final cure per treatment arm	180 days
Proportion of cured patients at day 180	To determine the proportion with 95% CI of patients that reach cure without relapsed or worsening at day 180 for the three treatment arms	180 days
Quality of life - patient reported outcome	To compare change over time of patient-reported outcomes - the dermatological life quality index (DLQI) scores and global assessment - per treatment arm	180 days
Safety and acceptability	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	180 days
Stability microbial diversity	To determine the stability of microbial diversity in the healthy skin over time	180 days
Increase microbial diversity	To assess the increase in microbial diversity indices within each trial arm at D14, EoT, D42 and M6 compared to D0.	180 days
Correlation microbial diversity and substantial improvement	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	180 days
Correlation microbial diversity and cure without relapse	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	180 days

Collaborators and Investigators

• Sponsor: Institute of Tropical Medicine, Belgium
• Collaborators: Arba Minch University; Armauer Hansen Research Institute (AHRI), Ethiopia
• Investigators: Principal Investigator: Johan Van Griensven, Prof, Head of department of clinical sciences

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: November 8, 2024
• First Submitted That Met QC Criteria: November 16, 2024
• First Posted (Estimated): November 19, 2024

Study Record Updates

• Last Update Posted (Estimated): November 19, 2024
• Last Update Submitted That Met QC Criteria: November 16, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Cutaneous Leishmania; Complicated cutaneous leishmania
• Additional Relevant MeSH Terms: Vector Borne Diseases; Infections; Protozoan Infections; Parasitic Diseases; Skin Diseases; Skin Diseases, Infectious; Skin Diseases, Parasitic; Euglenozoa Infections; Leishmaniasis; Leishmaniasis, Cutaneous; Anti-Bacterial Agents; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Synthesis Inhibitors; Fusidic Acid
• Other Study ID Numbers: AIM-CL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No