Intralesional Voriconazole, or Intralesional Cryotherapy, or Oral Doxycycline in the Treatment of Cutaneous Leishmaniasis

Study Overview
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Brief Summary
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Leishmaniasis is a vector-borne disease caused by obligate, intracellular protozoa of the genus Leishmania and transmitted by phlebotomine sandflies. It is found mostly in tropical and subtropical areas then it has spread into southern Europe. Increased international travel and immigration have led to an increased diagnosis of leishmaniasis cases in nonendemic areas (Kollipara et al., 2016). Foci of CL, caused by L. ma¬jor, occur in Afghanistan, Egypt, Iran, Iraq, Jordan, Libya, Morocco, Palestine, Pakistan, Saudi Arabia, Sudan, Syria, Tunisia, and Yemen. Many researchers have studied leishmaniasis in the endemic northern African countries, e.g., Morocco, Algeria, Tunisia, Egypt, and Libya. One of the established endemic leishmaniasis Libyan provinces is Al-jabal Al-gharbi province, where CL comprises a major parasitic health problem (Abdellatif et al., 2013).To evaluate the efficacy of intralesional cryotherapy, intralesional Voriconazole, and oral doxycycline in the treatment of cutaneous leishmaniasis compared to the conventional treatment (intralesional SSG).

Detailed Description
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Cutaneous leishmaniasis is a prevalent parasitic infection in northern Africa. In Egypt, CL cases are detected mainly in eastern governorates including Sinai. Cutaneous leishmaniasis represent a socioeconomic burden on the affected communities. Available treatment options are expensive and associated with systemic toxicity. There are alarming reports of emerging resistance against the currently in use therapeutics. Comparative controlled trials for the effective and the least harmful treatment modalities are lacking. Up to our knowledge this is the first study investigating the effectiveness of intralesional Voriconazole and intralesional cryotherapy in the treatment of cutaneous leishmaniasis So in this study the following objectives are being aimed: To evaluate the effectiveness and safety of intralesional Voriconazole comparing it to the intralesional SSG in patients with CL. To evaluate the effectiveness and safety of intralesional cryotherapy comparing it to the intralesional SSG in patients with CL. To evaluate the effectiveness and safety of Oral doxycycline comparing it to the intralesional SSG in patients with CL.

Official Title
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Efficacy of Intralesional Voriconazole Versus Intralesional Cryotherapy Versus Intralesional Sodium Stibogluconate Versus Oral Doxycycline in the Treatment of Acute Cutaneous Leishmaniasis

Conditions
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Leishmaniasis, Cutaneous

Intervention / Treatment
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* Drug: Intralesional Sodium stibogluconate
* Procedure: Intralesional Cryotherapy
* Drug: Intralesional Voriconazole
* Drug: Oral doxycycline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All participants must be willing to sign informed consent, for patients younger than 18 years old, parents or guardians will sign an informed consent. Patients clinically diagnosed with cutaneous leishmaniasis and confirmed using parasitological Giemsa-stained direct smears. Acute lesions of less than 12-week duration to exclude any possibility of natural self-healing of the lesions during follow-up. Both sexes. Age: > 12 years old. Exclusion Criteria: • Pregnancy and lactation. Patients < 12 years old. Patients with negative Giemsa stained direct smears. Patients with concomitant renal or liver impairment, congestive heart failure, uncontrolled diabetes mellitus, peripheral neuropathy, poor peripheral circulation, and prolonged corticosteroid therapy. Patients with lesions of more than 12 weeks duration. Patients with lesions > 5cm2 History of anti-Leishmania therapy in the last 3 months. For the intralesional groups the presence of > 5 lesions. Lesions in the perimeter (< 2 cm) of mucosal areas e.g. eyes, nose, mouth, or genitals. Patients with known hypersensitivity or allergy to the assigned drugs.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intralesional Sodium stibogluconate<br>Patients will receive intralesional infiltration of (SSG) at a dose of 50 mg/0.5 ml (0.2-0.4ml) maximum dose per session 1-3 ml. Sessions will be held once weekly for a maximum of 6 weeks. | Drug: Intralesional Sodium stibogluconate<br>* Sessions will be held once weekly for a maximum of 6 weeks<br>* Other names: SSG;|
| Experimental: intralesional Cryotherapy<br>Patients will be treated with intralesional Cryotherapy. Sessions will be held every two weeks till complete cure or a maximum of 6 sessions | Procedure: Intralesional Cryotherapy<br>* Intralesional Cryotherapy. Sessions will be held every two weeks<br>|
| Experimental: Intralesional Voriconazole<br>Patients will be treated with intralesional Voriconazole weekly till complete cure or a maximum of 6 sessions | Drug: Intralesional Voriconazole<br>* Weekly intralesional Voriconazole<br>* Other names: Vfend;|
| Experimental: Oral doxycycline<br>Patients will be treated with oral doxycycline, 200 mg daily, until complete cure or a maximum of 6 weeks | Drug: Oral doxycycline<br>* 200 mg daily for 6 weeks or till complete cure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response to treatment | The responses will be graded by an investigator who don't perform the injections. The clinical response will be graded based on the improvement percentage of the lesion in terms of size, erythema, inflammation, edema and ulcer re-epithelialization | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistence of clinical response | Persistence of clinical response at the end of follow-up period | 12 week post treatment termination | 
| Patient compliance | The percentage of patients continued the study in each arm | 6 weeks |