Topical Paromomycin for Cutaneous Leishmaniasis in Bolivia

NCT03096457 | Completed Phase 2

• 1 other identifier: ABF-BO-2016-102
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

This protocol will compare topical paromomycin to standard intralesional (IL) antimony (Sb) to placebo for L braziliensis in Bolivia.

Conditions

Leishmaniasis, Cutaneous; Leishmania Braziliensis Complex; Leishmaniasis, American; Leishmaniasis; American, Cutaneous

Keywords

leishmaniasis; L.braziliensis; paromomycin cream; intralesional pentamidine; leishmaniasis local therapy

Outcome Measures

Primary Outcomes (1)

• Change of Lesion size

  change of lesion area at 6 months after treatment compared to baseline

  6 months

Secondary Outcomes (1)

• Number of participants with treated-related adverse events

  1 month

Study Arms (3)

Group 1 - Paromomycin cream

EXPERIMENTAL

40 subjects will be included to receive 15% paromomycin in aquafilm base twice a day during 20 consecutive days. The lesion will be cleaned , then, a generous amount of the study drug (an amount sufficient to cover the area of the ulcer and the lesion border) will be applied to the lesion and rubbed into the ulcer using a gloved finger by a member of the clinical study staff. After application of the study drug, the patient will be observed for 15 minutes for signs of adverse events. If there are no signs of local toxicity, the area of the ulcer will be covered with extra study drug. For Days 2-20, the study drug will be applied and the lesion covered with a sterile gauze and tape dressing as on Day 1.

Drug: Paromomycin Sulfate

Group 2. Local Injectable Pentamidine

ACTIVE COMPARATOR

20 subjects will be included to receive IL pentamidine \[Pentacarinat® Sanofi-Aventis: 30 mg/ml\] will administered at a dose of 120 ug (4 ul) per mm2 of lesion area 3 times (on days 1, 3, and 5) as per our previous experience. A small button of Xylocaine® will be applied by means of a thin needle at the four cardinal points of the lesion and then a small gauge (23g) needle will introduce the drug in each cardinal point. The needle will be moved in all directions to infiltrate of whole lesion and surrounding infiltrated area.

Drug: Pentamidine Isethionate

Group 3. Vehicle control

PLACEBO COMPARATOR

10% Urea en parafilm cream will be used in similar ways as paromomycin cream in group 1

Other: Placebo

Interventions

Paromomycin Sulfate DRUG

topical application 2 times a day during 20 days

Group 1 - Paromomycin cream

Pentamidine Isethionate DRUG

3 Intralesional injections at days 1,3 and 5

Group 2. Local Injectable Pentamidine

Placebo OTHER

topical application 2 times a day during 20 days

Group 3. Vehicle control

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Gender: Male or female
• Age: \>12 yrs of age
• Presentation: 1-to-2 ulcerative lesions, each \< 30 mm in largest diameter and with a total lesion area \<900 mm2.
• Parasitology: Parasitological confirmation of the lesion will be made by visualization or culture of Leishmania from the biopsy or aspirate of the lesion.

You may not qualify if:

• Previous treatment for leishmaniasis with Sb, pentamidine, amphotericin B, miltefosine, imidazoles, allopurinol in the last 3 months.
• Other diseases that would be likely in the PI's opinion to interact, either positively or negatively, with treatment.

Sponsors & Collaborators

• Fundacion Nacional de Dermatologia: lead

Study Sites (2)

Hospital Local Palos Blancos

Palos Blancos, La Paz Department, 00000, Bolivia

Location

Hospital Dermatologico de Jorochito

Jorochito, SC, Bolivia

Location

Related Publications (6)

• Oliveira-Neto MP, Schubach A, Mattos M, da Costa SC, Pirmez C. Intralesional therapy of American cutaneous leishmaniasis with pentavalent antimony in Rio de Janeiro, Brazil--an area of Leishmania (V.) braziliensis transmission. Int J Dermatol. 1997 Jun;36(6):463-8. doi: 10.1046/j.1365-4362.1997.00188.x.

  PMID: 9248897 BACKGROUND

• Vasconcellos Ede C, Pimentel MI, Schubach Ade O, de Oliveira Rde V, Azeredo-Coutinho RB, Silva Fda C, Salgueiro Mde M, Moreira JS, Madeira Mde F, Baptista C, Valete-Rosalino CM. Intralesional meglumine antimoniate for treatment of cutaneous leishmaniasis patients with contraindication to systemic therapy from Rio de Janeiro (2000 to 2006). Am J Trop Med Hyg. 2012 Aug;87(2):257-60. doi: 10.4269/ajtmh.2012.11-0612.

  PMID: 22855754 BACKGROUND

• 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.

  PMID: 23390069 BACKGROUND

• Soto J, Paz D, Rivero D, Soto P, Quispe J, Toledo J, Berman J. Intralesional Pentamidine: A Novel Therapy for Single Lesions of Bolivian Cutaneous Leishmaniasis. Am J Trop Med Hyg. 2016 Apr;94(4):852-6. doi: 10.4269/ajtmh.15-0640. Epub 2016 Feb 22.

  PMID: 26903605 BACKGROUND

• Ben Salah A, Ben Messaoud N, Guedri E, Zaatour A, Ben Alaya N, Bettaieb J, Gharbi A, Belhadj Hamida N, Boukthir A, Chlif S, Abdelhamid K, El Ahmadi Z, Louzir H, Mokni M, Morizot G, Buffet P, Smith PL, Kopydlowski KM, Kreishman-Deitrick M, Smith KS, Nielsen CJ, Ullman DR, Norwood JA, Thorne GD, McCarthy WF, Adams RC, Rice RM, Tang D, Berman J, Ransom J, Magill AJ, Grogl M. Topical paromomycin with or without gentamicin for cutaneous leishmaniasis. N Engl J Med. 2013 Feb 7;368(6):524-32. doi: 10.1056/NEJMoa1202657.

  PMID: 23388004 BACKGROUND

• Soto J, Soto P, Ajata A, Luque C, Tintaya C, Paz D, Rivero D, Berman J. Topical 15% Paromomycin-Aquaphilic for Bolivian Leishmania braziliensis Cutaneous Leishmaniasis: A Randomized, Placebo-controlled Trial. Clin Infect Dis. 2019 Feb 15;68(5):844-849. doi: 10.1093/cid/ciy619.

  PMID: 30260376 DERIVED

MeSH Terms

Conditions

Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Leishmaniasis

Interventions

Paromomycin; Pentamidine

Condition Hierarchy (Ancestors)

Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Vector Borne Diseases; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Aminoglycosides; Glycosides; Carbohydrates; Benzamidines; Amidines; Organic Chemicals

Study Officials

• JAIME SOTO, MD

  Fundacion Nacional de Dermatologia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Group 1 (Paromomycin cream) will be compared to Group 3 (Vehicle cream). Both creams will have very similar physical characteristics and package. Group 2 (intralesional injection of pentamidine) will not be masked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomized between Paromomycin cream applied topically once daily for 20 days (group 1--40 patients), pentamidine administered intralesionally at 120 ug/mm2 on days 1, 3, 5 (group 2-20 patients), and cream vehicle applied topically once daily for 20 days (group 3-20 patients).

Study Record Dates

• First Submitted: March 9, 2017
• First Posted: March 30, 2017
• Study Start: April 15, 2017
• Primary Completion: March 18, 2018
• Study Completion: April 1, 2018
• Last Updated: February 2, 2021

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

BO (2)