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

Phase 3

Recruiting

• Conditions: Leishmaniasis, Cutaneous
• Interventions: Drug: Oral doxycycline; Drug: Intralesional Voriconazole; Drug: Intralesional Sodium stibogluconate; Procedure: Intralesional Cryotherapy

• Registration Number: NCT05708625
• Lead Sponsor: Zagazig University

Brief Summary

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

* 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:

1. To evaluate the effectiveness and safety of intralesional Voriconazole comparing it to the intralesional SSG in patients with CL.

2. To evaluate the effectiveness and safety of intralesional cryotherapy comparing it to the intralesional SSG in patients with CL.

3. To evaluate the effectiveness and safety of Oral doxycycline comparing it to the intralesional SSG in patients with CL.

Study Timeline

• Study Start: 2022-01-01
• Study First Submitted: 2023-01-22
• Study First Submitted QC: 2023-01-31
• Study First Posted: 2023-02-01
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-27
• Last Update Posted: 2023-08-29
• Primary Completion: 2023-12-01
• Study Completion: 2024-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 136

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.

  1. Patients clinically diagnosed with cutaneous leishmaniasis and confirmed using parasitological Giemsa-stained direct smears.
  2. Acute lesions of less than 12-week duration to exclude any possibility of natural self-healing of the lesions during follow-up.
  3. Both sexes.
  4. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oral doxycycline	Oral doxycycline	Patients will be treated with oral doxycycline, 200 mg daily, until complete cure or a maximum of 6 weeks
Intralesional Voriconazole	Intralesional Voriconazole	Patients will be treated with intralesional Voriconazole weekly till complete cure or a maximum of 6 sessions
Intralesional Sodium stibogluconate	Intralesional Sodium stibogluconate	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.
intralesional Cryotherapy	Intralesional Cryotherapy	Patients will be treated with intralesional Cryotherapy. Sessions will be held every two weeks till complete cure or a maximum of 6 sessions

Primary Outcome Measures

Name	Time	Method
Clinical response to treatment	6 weeks	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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Dermatology department, Gharyan University Hospitals, Medical College, Gharyan University; 🇱🇾 Gharyan, Select Region, Libyan Arab Jamahiriya