Low Antimonial Dosage in American Mucosal Leishmaniasis

NCT01301937 | Unknown Phase 2 DMC

• 1 other identifier: low dosage ML
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

"Phase III clinical trial for mucosal or mucocutaneous leishmaniasis. Equivalence between the standard and alternative schemes with meglumine antimoniate" has begun in October 2008 at the Laboratory of Leishmaniasis Surveillance at Evandro Chagas Clinical Research Institute (IPEC), FIOCRUZ, aiming to compare efficacy and safety of the standard recommended schedule with an alternative regimen of meglumine antimoniate (MA) in the treatment of mucosal or mucocutaneous leishmaniasis (ML or MCL)). It is a study with blind evaluation by the doctors and the responsible for statistical analysis. Patients diagnosed with Ml or MCL, eligible for the trial, are randomly allocated into one of the schemes with meglumine antimoniate and monitored before, during and after it. There is no single regimen applicable to all forms of leishmaniasis around the world. Therapeutic regimens applied to treat people living in other geographic areas result in mixed outcomes. Ideally, the most appropriate regimens should be established for each endemic area, based on its efficacy, toxicity, difficulties of administration and cost. Given the problems and limitations of the use of pentavalent antimonials at 20 mg / kg / day, a less toxic alternative regimen with 5mg/kg/day, continuous up to the cure deserves to be better evaluated. Treatment must lead to the healing of mucosal lesions and prevent late scarring tissues and disabilities development. The indication of high doses of MA is based on the evidence that there could be induction of resistance with use of subdoses. However, clinical studies with extended follow-up in Rio de Janeiro have suggested that regular low MA doses (5mg / kg / day) in a systemic way may constitute an effective scheme, achieving cure rates similar to higher dose, with lower toxicity, ease of implementation and lower cost. Published studies on efficacy and safety of alternative schemes with meglumine antimoniate failed to provide conclusive results, for various methodological biases. The need to compare the effectiveness and safety between treatment schemes with meglumine antimoniate currently recommended in Brazil for the treatment of ML or MCL and an alternative scheme with low dose of antimony is the motive for this study in Rio de Janeiro.

Conditions

Mucosal Leishmaniasis; Mucocutaneous Leishmaniasis

Keywords

Mucosal Leishmaniasis; Leishmania braziliensis; Meglumine Antimoniate; Treatment Effectiveness; Controlled Clinical Trials, Randomized

Outcome Measures

Primary Outcomes (1)

• Efficacy of meglumine antimoniate in the treatment of mucosal leishmaniasis

  This study is designed to evaluate the efficacy of high and low doses of meglumine antimoniate in the treatment of mucosal or mucocutaneous leishmaniasis.

  6 years

Secondary Outcomes (1)

• Safety of meglumine antimoniate in the treatment of mucosal leishmaniasis

  6 years

Study Arms (2)

High continuous dose

ACTIVE COMPARATOR

Meglumine antimoniate 20 mg/kg/day for 30 continuous days

Drug: Meglumine antimoniate

Low continuous dose

ACTIVE COMPARATOR

Meglumine antimoniate 5 mg/kg/day for up to 120 continuous days according to clinical cure

Drug: Meglumine antimoniate

Interventions

Meglumine antimoniate DRUG

Meglumine antimoniate (Aventis, São Paulo, Brazil) is stored and ministered under actual conditions employed by the health services in Brazil. Each patient will be included in one of two treatment groups with meglumine antimoniate IM: 1. High continuous dose: 20 mg/kg/day for 30 continuous days. 2. Low continuous dose 5 mg/kg/day for up to 120 continuous days. There will be no cross-over between the groups for the purpose of this study. The data from those patients who require permanent discontinuation of a scheme will be assessed in the group that were randomized, ie, by intention to treat Arms: High continuous dose, Low continuous dose

Also known as: Glucantime

High continuous dose; Low continuous dose

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Mucosal or mucocutaneous leishmaniasis with parasitological diagnosis by one or more of the following methods: direct examination (imprint), histopathology, culture, immunohistochemistry, or PCR.

You may not qualify if:

• Women who do not use contraceptives or do it badly
• Pregnant women
• Children under 13 years
• Previous antimonial treatment for LM
• Immunosuppressive therapy (steroids, cancer chemotherapy) or medicines for tuberculosis or leprosy.
• Presence of altered baseline clinical adverse effect level equivalent to \> G3
• Presence of altered basal laboratory adverse effect level equivalent to \> G2
• Presence of baseline electrocardiographic changes equivalent to an adverse effect level \> G4 and / or baseline QTc \> 0.46 ms (equivalent to AE level G1)

Sponsors & Collaborators

• Oswaldo Cruz Foundation: lead
• Rio de Janeiro State Research Supporting Foundation (FAPERJ): collaborator
• Conselho Nacional de Desenvolvimento Científico e Tecnológico: collaborator

Study Sites (1)

Oswaldo Cruz Foundation - IPEC/FIOCRUZ

Rio de Janeiro, 21040-360, Brazil

RECRUITING

Related Publications (18)

• Antezana G, Zeballos R, Mendoza C, Lyevre P, Valda L, Cardenas F, Noriega I, Ugarte H, Dedet JP. Electrocardiographic alterations during treatment of mucocutaneous leishmaniasis with meglumine antimoniate and allopurinol. Trans R Soc Trop Med Hyg. 1992 Jan-Feb;86(1):31-3. doi: 10.1016/0035-9203(92)90427-e.

  PMID: 1566297 BACKGROUND

• de Azeredo-Coutinho RB, Mendonca SC. An intermittent schedule is better than continuous regimen of antimonial therapy for cutaneous leishmaniasis in the municipality of Rio de Janeiro, Brazil. Rev Soc Bras Med Trop. 2002 Sep-Oct;35(5):477-81. doi: 10.1590/s0037-86822002000500009.

  PMID: 12621667 BACKGROUND

• Chulay JD, Spencer HC, Mugambi M. Electrocardiographic changes during treatment of leishmaniasis with pentavalent antimony (sodium stibogluconate). Am J Trop Med Hyg. 1985 Jul;34(4):702-9. doi: 10.4269/ajtmh.1985.34.702.

  PMID: 2992303 BACKGROUND

• Deps PD, Viana MC, Falqueto A, Dietze R. [Comparative assessment of the efficacy and toxicity of N-methyl-glucamine and BP88 sodium stibogluconate in the treatment of localized cutaneous leishmaniasis]. Rev Soc Bras Med Trop. 2000 Nov-Dec;33(6):535-43. doi: 10.1590/s0037-86822000000600004. Portuguese.

  PMID: 11175583 BACKGROUND

• Hepburn NC, Nolan J, Fenn L, Herd RM, Neilson JM, Sutherland GR, Fox KA. Cardiac effects of sodium stibogluconate: myocardial, electrophysiological and biochemical studies. QJM. 1994 Aug;87(8):465-72.

  PMID: 7922300 BACKGROUND

• Hepburn NC, Siddique I, Howie AF, Beckett GJ, Hayes PC. Hepatotoxicity of sodium stibogluconate therapy for American cutaneous leishmaniasis. Trans R Soc Trop Med Hyg. 1994 Jul-Aug;88(4):453-5. doi: 10.1016/0035-9203(94)90432-4.

  PMID: 7570843 BACKGROUND

• Marzochi MC, Marzochi KB. Tegumentary and visceral leishmaniases in Brazil: emerging anthropozoonosis and possibilities for their control. Cad Saude Publica. 1994;10 Suppl 2:359-75. doi: 10.1590/s0102-311x1994000800014. Epub 2004 Mar 19.

  PMID: 15042226 BACKGROUND

• McBride MO, Linney M, Davidson RN, Weber JN. Pancreatic necrosis following treatment of leishmaniasis with sodium stibogluconate. Clin Infect Dis. 1995 Sep;21(3):710. doi: 10.1093/clinids/21.3.710. No abstract available.

  PMID: 8527590 BACKGROUND

• Oliveira Neto MP, Schubach A, Araujo ML, Pirmez C. High and low doses of antimony (Sbv) in American cutaneous leishmaniasis. A five years follow-up study of 15 patients. Mem Inst Oswaldo Cruz. 1996 Mar-Apr;91(2):207-9. doi: 10.1590/s0074-02761996000200016.

  PMID: 8736092 BACKGROUND

• 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

• Oliveira-Neto MP, Schubach A, Mattos M, Goncalves-Costa SC, Pirmez C. A low-dose antimony treatment in 159 patients with American cutaneous leishmaniasis: extensive follow-up studies (up to 10 years). Am J Trop Med Hyg. 1997 Dec;57(6):651-5. doi: 10.4269/ajtmh.1997.57.651.

  PMID: 9430521 BACKGROUND

• Oliveira-Neto MP, Schubach A, Mattos M, Goncalves-Costa SC, Pirmez C. Treatment of American cutaneous leishmaniasis: a comparison between low dosage (5 mg/kg/day) and high dosage (20 mg/kg/day) antimony regimens. Pathol Biol (Paris). 1997 Jun;45(6):496-9.

  PMID: 9309267 BACKGROUND

• Ribeiro AL, Drummond JB, Volpini AC, Andrade AC, Passos VM. Electrocardiographic changes during low-dose, short-term therapy of cutaneous leishmaniasis with the pentavalent antimonial meglumine. Braz J Med Biol Res. 1999 Mar;32(3):297-301. doi: 10.1590/s0100-879x1999000300008.

  PMID: 10347787 BACKGROUND

• Rodrigues ML, Costa RS, Souza CS, Foss NT, Roselino AM. Nephrotoxicity attributed to meglumine antimoniate (Glucantime) in the treatment of generalized cutaneous leishmaniasis. Rev Inst Med Trop Sao Paulo. 1999 Jan-Feb;41(1):33-7. doi: 10.1590/s0036-46651999000100007.

  PMID: 10436668 BACKGROUND

• Sampaio RN, de Paula CD, Sampaio JH, Furtado Rde S, Leal PP, Rosa TT, Rodrigues ME, Veiga JP. [The evaluation of the tolerance and nephrotoxicity of pentavalent antimony administered in a dose of 40 mg Sb V/kg/day, 12/12 hr, for 30 days in the mucocutaneous form of leishmaniasis]. Rev Soc Bras Med Trop. 1997 Nov-Dec;30(6):457-63. doi: 10.1590/s0037-86821997000600003. Portuguese.

  PMID: 9463192 BACKGROUND

• Schubach Ade O, Marzochi KB, Moreira JS, Schubach TM, Araujo ML, Vale AC, Passos SR, Marzochi MC. Retrospective study of 151 patients with cutaneous leishmaniasis treated with meglumine antimoniate. Rev Soc Bras Med Trop. 2005 May-Jun;38(3):213-7. doi: 10.1590/s0037-86822005000300001. Epub 2005 May 4.

  PMID: 15895170 BACKGROUND

• Sharquie KE. A new intralesional therapy of cutaneous leishmaniasis with hypertonic sodium chloride solution. J Dermatol. 1995 Oct;22(10):732-7. doi: 10.1111/j.1346-8138.1995.tb03911.x.

  PMID: 8586751 BACKGROUND

• Veiga JP, Wolff ER, Sampaio RN, Marsden PD. Renal tubular dysfunction in patients with mucocutaneous leishmaniasis treated with pentavalent antimonials. Lancet. 1983 Sep 3;2(8349):569. doi: 10.1016/s0140-6736(83)90595-0. No abstract available.

  PMID: 6136717 BACKGROUND

MeSH Terms

Conditions

Leishmaniasis, Mucocutaneous

Interventions

Meglumine Antimoniate

Condition Hierarchy (Ancestors)

Leishmaniasis, Cutaneous; Leishmaniasis; 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)

Meglumine; Sorbitol; Sugar Alcohols; Alcohols; Organic Chemicals; Hexosamines; Amino Sugars; Carbohydrates

Study Officials

• Armando O. Schubach, MD, PhD

  IPEC/FIOCRUZ

  STUDY DIRECTOR

Central Study Contacts

Armando O. Schubach, MD, PhD

CONTACT

(55)(21)38659541; vigileish@ipec.fiocruz.br

Claudia M. Valete-Rosalino, MD, PhD

CONTACT

(55)(21)38659541; vigileish@ipec.fiocruz.br

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Researcher

Study Record Dates

• First Submitted: February 20, 2011
• First Posted: February 23, 2011
• Study Start: October 1, 2008
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2021
• Last Updated: July 12, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)