Clinical trial NCT05708625: Intralesional Voriconazole, or Intralesional Cryotherapy, or Oral Doxycycline in the Treatment of Cutaneous Leishmaniasis
Official title: Efficacy of Intralesional Voriconazole Versus Intralesional Cryotherapy Versus Intralesional Sodium Stibogluconate Versus Oral Doxycycline in the Treatment of Acute Cutaneous Leishmaniasis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Leishmaniasis, Cutaneous
Lead sponsor: Zagazig University
Sponsor class: OTHER_GOV
First posted: 2023-02-01
Enrollment: 136
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Clinical response to treatment
timeFrame: 6 weeks
Secondary outcomes:
measure: Persistence of clinical response
timeFrame: 12 week post treatment termination
measure: Patient compliance
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Gharyan
country: Libyan Arab Jamahiriya
facility: Dermatology department, Gharyan University Hospitals, Medical College, Gharyan University
state: Select Region
Study officials:
affiliation: Zagazig University
name: Hagar Nofal, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Akulinina IK, Berechikidze IA, Larina SN, Sakharova TV, Degtyarevskaya TY, Romanelli M. Effectiveness of doxycycline for the treatment of zoonotic cutaneous leishmaniasis in vivo. Parasitology. 2021 Mar;148(3):361-365. doi: 10.1017/S0031182020002152. Epub 2020 Nov 16.
citation: Asilian A, Sadeghinia A, Faghihi G, Momeni A. Comparative study of the efficacy of combined cryotherapy and intralesional meglumine antimoniate (Glucantime) vs. cryotherapy and intralesional meglumine antimoniate (Glucantime) alone for the treatment of cutaneous leishmaniasis. Int J Dermatol. 2004 Apr;43(4):281-3. doi: 10.1111/j.1365-4632.2004.02002.x.
citation: Bahrami S, Oryan A, Bemani E. Efficacy of amiodarone and voriconazole combination therapy in cutaneous leishmaniasis in the mice experimentally infected with Leishmania major. J Infect Chemother. 2021 Jul;27(7):984-990. doi: 10.1016/j.jiac.2021.02.011. Epub 2021 Feb 23.
citation: Daie Parizi MH, Karvar M, Sharifi I, Bahrampour A, Heshmat Khah A, Rahnama Z, Baziar Z, Amiri R. The topical treatment of anthroponotic cutaneous leishmaniasis with the tincture of thioxolone plus benzoxonium chloride (Thio-Ben) along with cryotherapy: a single-blind randomized clinical trial. Dermatol Ther. 2015 May-Jun;28(3):140-6. doi: 10.1111/dth.12229. Epub 2015 Apr 6.
citation: Soto J, Rojas E, Guzman M, Verduguez A, Nena W, Maldonado M, Cruz M, Gracia L, Villarroel D, Alavi I, Toledo J, Berman J. Intralesional antimony for single lesions of bolivian cutaneous leishmaniasis. Clin Infect Dis. 2013 May;56(9):1255-60. doi: 10.1093/cid/cit049. Epub 2013 Feb 6.