Treatment of cutaneous leishmaniasis with a sequential scheme of pentamidine and tamoxifen in an area with a predominance of Leishmania (Viannia) guyanensis: A randomised, non-inferiority clinical trial.
PCR
Western Amazon
clinical trial
cutaneous leishmaniasis
tamoxifen
telemedicine
treatment
Journal
Tropical medicine & international health : TM & IH
ISSN: 1365-3156
Titre abrégé: Trop Med Int Health
Pays: England
ID NLM: 9610576
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
medline:
5
12
2023
pubmed:
8
11
2023
entrez:
8
11
2023
Statut:
ppublish
Résumé
To determine whether a combination of a single intramuscular (IM) dose of pentamidine (7 mg/kg) followed by oral tamoxifen 40 mg/day for 20 days is non-inferior to three IM doses of pentamidine 7 mg/kg in the treatment of cutaneous leishmaniasis with a margin of 15%. Phase II, randomised, controlled, open-label, non-inferiority clinical trial. Primary outcome was the complete healing of the lesions 6 months after starting treatment. Secondary outcomes were healing 3 months after starting treatment and determining the presence and severity of adverse effects (AE). The research was concluded with 49 patients; Leishmania (Viannia) guyanensis was the most frequent species isolated. In the primary outcome, 18 (72%) (95% CI: 52.4%-85.7%) of the 25 patients allocated to the intervention group and 24 (100%) (95% CI: 86.2%-100%) of the control group (p = 0.015) met the established criteria of cure. There was no AE with tamoxifen. Although a 72% cure rate presented by the combination of tamoxifen and pentamidine was lower than in the control group that achieved a 100% cure, it is still a safe and is a clinically relevant result. It indicates that the therapeutic scheme evaluated may be a promising option for populations in remote areas, however it should be further studied, in order to include a larger number of patients.
Substances chimiques
Pentamidine
673LC5J4LQ
Antiprotozoal Agents
0
Tamoxifen
094ZI81Y45
Types de publication
Randomized Controlled Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
871-880Informations de copyright
© 2023 John Wiley & Sons Ltd.
Références
World Health Organization. Leishmaniasis, key facts [Internet]. WHO. 2022 [cited 2022 Dec 22]. Available from: https://www.who.int/en/news-room/fact-sheets/detail/leishmaniasis
Azeredo-Coutinho RB, Mendonça SCF. Formas clínicas das leishmanioses tegumentares nas Américas. In: Conceição-Silva F, Alves CR, editors. Leishmanioses do continente americano. 2nd ed. Rio de Janeiro: Editora Fiocruz; 2014. p. 311-326.
Silveira ST, Laison R, Coprbett CEP. Clinical and immunophatological spectrum of American cutaneous leishmaniasis with special reference to the disease in Amazonian Brazil: a review. Mem Inst Oswaldo Cruz. 2004;99(3):239-251.
Grimaldi G Jr, Tesh RB, McMahon-Pratt D. A review of the geographic distribution and epidemiology of leishmaniasis in the New World. Am J Trop Med Hyg. 1989;41(6):687-725. https://doi.org/10.4269/ajtmh.1989.41.687
Silveira FT. What makes mucosal and anergic diffuse cutaneous leishmaniases so clinically and immunopathogically different? A review in Brazil. Trans R Soc Trop Med Hyg. 2019;29:trz037. https://doi.org/10.1093/trstmh/trz037
Guerra JAO, Prestes SR, Silveira H, Coelho LIARC, Gama P, Moura A, et al. Mucosal leishmaniasis caused by Leishmania (Viannia) braziliensis and Leishmania (Viannia) guyanensis in the Brazilian Amazon. PLoS Negl Trop Dis. 2011;5(3):e980. https://doi.org/10.1371/journal.pntd.0000980
Coelho LICC, Paes M, Guerra JA, Barbosa MG, Coelho C, Lima B, et al. Characterization of Leishmania spp. causing cutaneous Leishmaniasis in Manaus, Amazonas, Brazil. Parasitol Res. 2011;108(3):671-677. https://doi.org/10.1007/s00436-010-2139-9
Boggild AK, Ramos AP, Espinosa D, Valencia BM, Veland N, Miranda-Verastegui C, et al. Clinical and demographic stratification of test performance: a pooled analysis of five laboratory diagnostic methods for American cutaneous Leishmaniasis. Am J Trop Med Hyg. 2010;83(2):345-350. https://doi.org/10.4269/ajtmh.2010.09-0414
de Almeida Benicio A, Gadelha EPN, Talhari A, da Silva RM Jr, Ferreira LC, dos Santos MCC, et al. Combining diagnostic procedures for the management of leishmaniasis in areas with high prevalence of Leishmania guyanensis. An Bras Dermatol. 2011;86(6):1141-1144. https://doi.org/10.1590/s0365-05962011000600012
Gomes CM, de Paula NA, Cesetti MV, Roselino AM, Sampaio RN. Mucocutaneous Leishmaniasis: accuracy and molecular validation of noninvasive procedures in a L. (V.) braziliensis-endemic area. Diagn Microbiol Infect Dis. 2014;79(4):413-418. https://doi.org/10.1016/j.diagmicrobio.2014.05.002
Ministério da Saúde (BR). Secretaria de Vigilância em Saúde, Departamento de Vigilância das Doenças Transmissíveis. Manual de Vigilância da Leishmaniose Tegumentar [Internet]. Brasília: Ministério da Saúde; 2017. p. 198 [cited 2022 Oct 23]. Available from: https://bvsms.saude.gov.br/bvs/publicacoes/manual_vigilancia_leishmaniose_tegumentar.pdf
Ministério da Saúde (BR), Secretaria de Ciência, Tecnologia e Insumos Estratégicos. Portaria n° 56. Brasília: 30 de outubro de; 2018. p. 198 [cited 2023 Feb 12]. Available from: http://138.68.60.75/images/portarias/outubro2018/dia31/portaria56.pdf
Ministério da Saúde (BR), Secretaria de Vigilância em Saúde, Departamento de Imunização e Doenças Transmissíveis, Coordenação-Geral de Vigilância de Zoonoses e Doenças de Transmissão Vetorial. Nota Informativa n° 13/2020-CGZV/DEIDT/SVS/MS. Brasília. 2020.
Neves LO, Talhari AC, Gadelha EPN, Silva-Junior RM, Guerra JAO, Ferreira LCL, et al. Estudo clinico randomizado comparando antimoniato de meglumina, pentamidina e anfotericina B para o tratamento da Leishmaniose Cutânea ocasionada por Leishmania (V.) guyanensis. An Bras Dermatol. 2011;86(6):1092-1101. https://doi.org/10.1590/S0365-05962011000600005
Gadelha EPN, Ramasawmy R, de Oliveira BC, Rocha NM, Guerra JAO, Silva GA, et al. An open label randomized clinical trial comparing the safety and effectiveness of one, two or three weekly pentamidine isethionate doses (seven milligrams per kilogram) in the treatment of cutaneous leishmaniasis in the Amazon region. PLoS Negl Trop Dis. 2018;12(10):e0006850. https://doi.org/10.1371/journal.pntd.0006850
Chrusciak-Talhari A, Dietze R, Talhari CC, da Silva RM, Yamashita EPG, de Oliveira Penna G, et al. Randomized controlled clinical trial to access efficacy and safety of miltefosine in the treatment of cutaneous Leishmaniasis caused by Leishmania (Viannia) guyanensis in Manaus, Brazil. Am J Trop Med Hyg. 2011;84(2):255-260. https://doi.org/10.4269/ajtmh.2011.10-0155
Mendes L, Guerra JO, Costa B, Silva ASD, Guerra MDGB, Ortiz J, et al. Association of miltefosine with granulocyte and macrophage colony-stimulating factor (GM-CSF) in the treatment of cutaneous leishmaniasis in the Amazon region: a randomized and controlled trial. Int J Infect Dis. 2021;103:358-363. https://doi.org/10.1016/j.ijid.2020.11.183
Machado PR, Ampuero J, Guimaraes LH, Villasboas L, Rocha AT, Schriefer A, et al. Miltefosine in the treatment of cutaneous Leishmaniasis caused by Leishmania braziliensis in Brazil: a randomized and controlled trial. PLoS Negl Trop Dis. 2010;4(12):1-6. https://doi.org/10.1371/journal.pntd.0000912
Machado PRL, Prates FVO, Boaventura V, Lago T, Guimarães LH, Schriefer A, et al. A double-blind, randomized trial to evaluate miltefosine and topical granulocyte macrophage colony-stimulating factor in the treatment of cutaneous Leishmaniasis caused by Leishmania braziliensis in Brazil. Clin Infect Dis. 2021;73(7):e2465-e2469. https://doi.org/10.1093/cid/ciaa1337
Miguel DC, Yokoyama-Yasunaka JK, Uliana SR. Tamoxifen is effective in the treatment of L. amazonensis infections in mice. PLoS Negl Trop Dis. 2008;2:e249.
Miguel DC, Zauli-Nascimento RC, Yokoyama-Yasunaka JK, Katz S, Barbiéri CL, Uliana SR. Tamoxifen as a potential antileishmanial agent: efficacy in the treatment of Leishmania braziliensis and Leishmania chagasi infections. J Antimicrob Chemother. 2009;63:365-368.
Miguel DC, Yokoyama-Yasunaka JK, Andreoli WK, Mortara RA, Uliana SR. Tamoxifen is effective against Leishmania and induces a rapid alkalinization of parasitophorous vacuoles harbouring Leishmania (Leishmania) amazonensis amastigotes. J Antimicrob Chemother. 2007;60(3):526-534. https://doi.org/10.1093/jac/dkm219
Altan N, Chen Y, Schindler M, Simon SM. Tamoxifen inhibits acidification in cells independent of the estrogen receptor. Proc Natl Acad Sci U S A. 1999;96(8):4432-4437. https://doi.org/10.1073/pnas.96.8.4432
Machado PRL, Ribeiro CS, França-Costa J, Dourado MEF, Trinconi CT, Yokoyama-Yasunaka JKU, et al. Tamoxifen and meglumine antimoniate combined therapy in cutaneous leishmaniasis patients: a randomised trial. Trop Med Int Health. 2018;23(9):936-942. https://doi.org/10.1111/tmi.13119
Palacios J, Yildiz A, Young AH, Taylor MJ. Tamoxifen for bipolar disorder: systematic review and meta-analysis. J Psychopharmacol. 2019;33(2):177-184. https://doi.org/10.1177/0269881118822167
Farrar MC, Jacobs TF. Tamoxifen. In: StatPearls, editor. Treasure Island, FL: StatPearls Publishing; 2023 Jan [Updated 2023 Apr 10; cited 2023 Sep 1]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532905/
Husein-ElAhmed H, Gieler U, Steinhoff M. Evidence supporting the enhanced efficacy of pentavalent antimonials with adjuvant therapy for cutaneous leishmaniasis: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2020;34(10):2216-2228. https://doi.org/10.1111/jdv.16333
Berbert TRN, de Mello TFP, Wolf Nassif P, Mota CA, Silveira AV, Duarte GC, et al. Pentavalent antimonials combined with other therapeutic alternatives for the treatment of cutaneous and mucocutaneous leishmaniasis: a systematic review. Dermatol Res Pract. 2018;2018:9014726. https://doi.org/10.1155/2018/9014726
Comissão Nacional de Ética em Pesquisa. Secretaria-executiva do Conselho Nacional de Saúde, Ministério da Saúde (Brasil). Carta circular n° 1/2021-CONEP/SECNS/MS. Orientações para procedimentos em pesquisas com qualquer etapa em ambiente virtual. Brasília. 2021.
Graça GC, Volpini AC, Romero GA, Oliveira Neto MP, Hueb M, Porrozzi R, et al. Development and validation of PCR-based assays for diagnosis of American cutaneous Leishmaniasis and identification of the parasite species. Mem Inst Oswaldo Cruz. 2012;107(5):664-674. https://doi.org/10.1590/s0074-02762012000500014
Briones Nieva CA, Cid AG, Romero AI, García-Bustos MF, Villegas M, Bermúdez JM. An appraisal of the scientific current situation and new perspectives in the treatment of cutaneous leishmaniasis. Acta Trop. 2021;221:105988. https://doi.org/10.1016/j.actatropica.2021.105988
Sands M, Kron MA, Brown RB. Pentamidine: a review. Rev Infect Dis. 1985;7(5):625-634. https://doi.org/10.1093/clinids/7.5.625
Pandit MK, Burke J, Gustafson AB, Minocha A, Peiris AN. Drug-induced disorders of glucose tolerance. Ann Intern Med. 1993;118(7):529-539. https://doi.org/10.7326/0003-4819-118-7-199304010-00008
Dorlo TPC, Kager PA. Pentamidine dosage: a base/salt confusion. PLoS Negl Trop Dis. 2008;2:225.
Owusu C, Buist DS, Field TS, Lash TL, Thwin SS, Geiger AM, et al. Predictors of tamoxifen discontinuation among older women with estrogen receptor-positive breast cancer. J Clin Oncol. 2008;26(4):549-555. https://doi.org/10.1200/JCO.2006.10.1022
Amrollahi Z, Rezaei F, Salehi B, Modabbernia AH, Maroufi A, Esfandiari GR, et al. Double-blind, randomized, placebo-controlled 6-week study on the efficacy and safety of the tamoxifen adjunctive to lithium in acute bipolar mania. J Affect Disord. 2011;129:327-331.
Buonomo B, Brunello A, Noli S, Miglietta L, Del Mastro L, Lambertini M, et al. Tamoxifen exposure during pregnancy: a systematic review and three more cases. Breast Care (Basel). 2020;15(2):148-156. https://doi.org/10.1159/000501473
Sindermann H, Engel J. Development of miltefosine as an oral treatment for leishmaniasis. Trans R Soc Trop Med Hyg. 2006;100:S17-S20.
Kip AE, Schellens JHM, Beijnen JH, Dorlo TPC. Clinical pharmacokinetics of systemically administered antileishmanial drugs. Clin Pharmacokinet. 2018;57(2):151-176. https://doi.org/10.1007/s40262-017-0570-0
Olliaro P, Vaillant M, Arana B, Grogl M, Modabber F, Magill A, et al. Methodology of clinical trials aimed at assessing interventions for cutaneous leishmaniasis. PLoS Negl Trop Dis. 2013;7(3):e2130. https://doi.org/10.1371/journal.pntd.0002130
Harms G, Chehade AK, Douba M, Roepke M, Mouakeh A, Rosenkaimer F, et al. A randomized trial comparing a pentavalent antimonial drug and recombinant interferon-gamma in the local treatment of cutaneous leishmaniasis. Trans R Soc Trop Med Hyg. 1991;85(2):214-216. https://doi.org/10.1016/0035-9203(91)