Effect of Montelukast in Preventing Dengue With Warning Signs in Dengue Patients

Summary

This study aims to determine the efficacy of montelukast in reducing the incidence of dengue warning signs in adult dengue patients.

Timeline

Start

2021-01-15

Primary completion

2023-06-17

Completion

2023-06-17

Publications

• Background Guzman MG, Gubler DJ, Izquierdo A, Martinez E, Halstead SB. Dengue infection. Nat Rev Dis Primers. 2016 Aug 18;2:16055. doi: 10.1038/nrdp.2016.55.
• Background L'Azou M, Moureau A, Sarti E, Nealon J, Zambrano B, Wartel TA, Villar L, Capeding MR, Ochiai RL; CYD14 Primary Study Group; CYD15 Primary Study Group. Symptomatic Dengue in Children in 10 Asian and Latin American Countries. N Engl J Med. 2016 Mar 24;374(12):1155-66. doi: 10.1056/NEJMoa1503877.
• Background Wilder-Smith A, Ooi EE, Horstick O, Wills B. Dengue. Lancet. 2019 Jan 26;393(10169):350-363. doi: 10.1016/S0140-6736(18)32560-1.
• Background Srikiatkhachorn A, Krautrachue A, Ratanaprakarn W, Wongtapradit L, Nithipanya N, Kalayanarooj S, Nisalak A, Thomas SJ, Gibbons RV, Mammen MP Jr, Libraty DH, Ennis FA, Rothman AL, Green S. Natural history of plasma leakage in dengue hemorrhagic fever: a serial ultrasonographic study. Pediatr Infect Dis J. 2007 Apr;26(4):283-90; discussion 291-2. doi: 10.1097/01.inf.0000258612.26743.10.
• Background Bethell DB, Flobbe K, Cao XT, Day NP, Pham TP, Buurman WA, Cardosa MJ, White NJ, Kwiatkowski D. Pathophysiologic and prognostic role of cytokines in dengue hemorrhagic fever. J Infect Dis. 1998 Mar;177(3):778-82. doi: 10.1086/517807.
• Background Srikiatkhachorn A, Green S. Markers of dengue disease severity. Curr Top Microbiol Immunol. 2010;338:67-82. doi: 10.1007/978-3-642-02215-9_6.
• Background Green S, Vaughn DW, Kalayanarooj S, Nimmannitya S, Suntayakorn S, Nisalak A, Lew R, Innis BL, Kurane I, Rothman AL, Ennis FA. Early immune activation in acute dengue illness is related to development of plasma leakage and disease severity. J Infect Dis. 1999 Apr;179(4):755-62. doi: 10.1086/314680.
• Background Avirutnan P, Punyadee N, Noisakran S, Komoltri C, Thiemmeca S, Auethavornanan K, Jairungsri A, Kanlaya R, Tangthawornchaikul N, Puttikhunt C, Pattanakitsakul SN, Yenchitsomanus PT, Mongkolsapaya J, Kasinrerk W, Sittisombut N, Husmann M, Blettner M, Vasanawathana S, Bhakdi S, Malasit P. Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement. J Infect Dis. 2006 Apr 15;193(8):1078-88. doi: 10.1086/500949. Epub 2006 Mar 9.
• Background Nascimento EJ, Silva AM, Cordeiro MT, Brito CA, Gil LH, Braga-Neto U, Marques ET. Alternative complement pathway deregulation is correlated with dengue severity. PLoS One. 2009 Aug 26;4(8):e6782. doi: 10.1371/journal.pone.0006782.
• Background Londono-Renteria B, Marinez-Angarita JC, Troupin A, Colpitts TM. Role of Mast Cells in Dengue Virus Pathogenesis. DNA Cell Biol. 2017 Jun;36(6):423-427. doi: 10.1089/dna.2017.3765. Epub 2017 May 9.
• Background St John AL, Rathore AP, Yap H, Ng ML, Metcalfe DD, Vasudevan SG, Abraham SN. Immune surveillance by mast cells during dengue infection promotes natural killer (NK) and NKT-cell recruitment and viral clearance. Proc Natl Acad Sci U S A. 2011 May 31;108(22):9190-5. doi: 10.1073/pnas.1105079108. Epub 2011 May 16.
• Background Schmutzler W, Bolsmann K, Zwadlo-Klarwasser G. Comparison of histamine release from human blood monocytes, lymphocytes, adenoidal and skin mast cells. Int Arch Allergy Immunol. 1995 May-Jun;107(1-3):194-6. doi: 10.1159/000236974.
• Background Marone G, Varricchi G, Loffredo S, Granata F. Mast cells and basophils in inflammatory and tumor angiogenesis and lymphangiogenesis. Eur J Pharmacol. 2016 May 5;778:146-51. doi: 10.1016/j.ejphar.2015.03.088. Epub 2015 May 2.
• Background St John AL, Rathore AP, Raghavan B, Ng ML, Abraham SN. Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage. Elife. 2013 Apr 30;2:e00481. doi: 10.7554/eLife.00481.
• Background Syenina A, Jagaraj CJ, Aman SA, Sridharan A, St John AL. Dengue vascular leakage is augmented by mast cell degranulation mediated by immunoglobulin Fcgamma receptors. Elife. 2015 Mar 18;4:e05291. doi: 10.7554/eLife.05291.
• Background Dahlen SE, Bjork J, Hedqvist P, Arfors KE, Hammarstrom S, Lindgren JA, Samuelsson B. Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: in vivo effects with relevance to the acute inflammatory response. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3887-91. doi: 10.1073/pnas.78.6.3887.
• Background Loke WM, Chow AY, Lam Mok Sing K, Lee CY, Halliwell B, Lim EC, Quek AM, Ooi EE, Seet RC. Augmentation of 5-lipoxygenase activity and expression during dengue serotype-2 infection. Virol J. 2013 Oct 30;10:322. doi: 10.1186/1743-422X-10-322.
• Background Sherif NA, Zayan AH, Elkady AH, Ghozy S, Ahmed AR, Omran ES, Taha EA, Eldesoky EA, Ebied A, Tieu T, Maraie N, Kamel MG, Ngo HT, Mattar OM, Hirayama K, Huy NT. Mast cell mediators in relation to dengue severity: A systematic review and meta-analysis. Rev Med Virol. 2020 Jan;30(1):e2084. doi: 10.1002/rmv.2084. Epub 2019 Nov 10.
• Background Rathore AP, Mantri CK, Aman SA, Syenina A, Ooi J, Jagaraj CJ, Goh CC, Tissera H, Wilder-Smith A, Ng LG, Gubler DJ, St John AL. Dengue virus-elicited tryptase induces endothelial permeability and shock. J Clin Invest. 2019 Jul 2;129(10):4180-4193. doi: 10.1172/JCI128426.
• Background Leo YS, Gan VC, Ng EL, Hao Y, Ng LC, Pok KY, Dimatatac F, Go CJ, Lye DC. Utility of warning signs in guiding admission and predicting severe disease in adult dengue. BMC Infect Dis. 2013 Oct 24;13:498. doi: 10.1186/1471-2334-13-498.
• Nitinai N, Nasomsong W, Chuerboonchai W, Tweekittikul A, Khingmontri V, Panuvatvanich B, Bangchuad T, Pongpraijaroen M, Roongfa-Ngarm T, Vasikasin V. Effect of montelukast in preventing dengue with warning signs among patients with dengue: A multicenter, randomized, double-blind, placebo-controlled trial. PLoS Negl Trop Dis. 2024 Feb 2;18(2):e0011927. doi: 10.1371/journal.pntd.0011927. eCollection 2024 Feb.

Drugs

Indications