Clinical trial NCT06695143: Antimicrobial Adjuvants to Revert the Imbalance of Skin Microbiota for Improved Outcomes of Complicated Cutaneous Leishmaniasis Treatment in Ethiopia
Official title: Antimicrobial Adjuvants to Revert the Imbalance of Skin Microbiota for Improved Outcomes of Complicated Cutaneous Leishmaniasis Treatment in Ethiopia
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Leishmaniasis, Cutaneous
Keywords: Cutaneous Leishmania
Complicated cutaneous leishmania
Lead sponsor: Institute of Tropical Medicine, Belgium
Sponsor class: OTHER
Collaborators: name: Armauer Hansen Research Institute (AHRI), Ethiopia
name: Arba Minch University
First posted: 2024-11-19
Enrollment: 180
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Improvement of index lesion at EoT
timeFrame: 28 days
Secondary outcomes:
measure: Arm 1 superiority to arm 3 - index lesion
timeFrame: 42 days
measure: Arm 1 superiority to arm 3 - lesions eligible for treatment
timeFrame: 42 days
measure: Proportion of participants that reach substiantial improvement - arm 1 vs arm 2
timeFrame: 42 days
measure: Proportion of participants that reach substiantial improvement - arm 2 vs arm 3
timeFrame: 42 days
measure: Cycles needed for final cure
timeFrame: 180 days
measure: Proportion of cured patients at day 180
timeFrame: 180 days
measure: Quality of life - patient reported outcome
timeFrame: 180 days
measure: Safety and acceptability
timeFrame: 180 days
measure: Stability microbial diversity
timeFrame: 180 days
measure: Increase microbial diversity
timeFrame: 180 days
measure: Correlation microbial diversity and substantial improvement
timeFrame: 180 days
measure: Correlation microbial diversity and cure without relapse
timeFrame: 180 days
Other outcomes:
Locations:
city: Arba Minch
country: Ethiopia
facility: Arba Minch General Hospital
city: Chencha
country: Ethiopia
facility: Chencha Primary Hospital
Study officials:
affiliation: Head of department of clinical sciences
name: Johan Van Griensven, Prof
role: PRINCIPAL_INVESTIGATOR
References: