Effect of Montelukast in Preventing Dengue With Warning Signs in Dengue Patients
NCT ID: NCT04673422
Last Updated: 2023-07-18
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2/PHASE3
358 participants
INTERVENTIONAL
2021-01-15
2023-06-17
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Effect of Loratadine/Montelukast Combination on Congestion in SAR Patients Exposed to Pollen in an EEU (Study P04822)
NCT00423995
A Study to Evaluate the Safety of Combination Montelukast/Loratadine in Mexican Participants With Allergic Rhinitis (MK-0476A-484)
NCT01673620
Montelukast - a Treatment Choice for COVID-19
NCT04714515
Impact Of Montelukast On Allergic Rhinitis And Its Inflammatory Makers
NCT05381207
An Approved Drug to Study a New Indication for Seasonal Allergic Rhinitis in Patients With Asthma (0476-269)
NCT00092885
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Mast cells have recently been acknowledged as an important regulator for promoting innate immune responses. Important composition of granules in mast cells are proteases, chymase and tryptase, histamine, heparin and leukotriene. The activated mast cells can undergo degranulation, releasing these cytokines. These increase capillary permeability, leading to vascular leakage.
Leukotriene has an important role in promoting plasma leakage and leukocyte adhesion in postcapillary venules. In dengue patients, leukotriene levels usually elevate during febrile and defervescence stage for 35 and 38 times of the baseline values, and return to baseline in convalescence stage. Blocking leukotriene in dengue infected mice can significantly reduce plasma leakage.
The management of dengue consists of only symptomatic treatment, and intravenous fluid replacement. No specific treatment has yet been demonstrated of a benefit in preventing complications. In the recent decades, mast cells have been demonstrated as a major contributor of severe forms of dengue, leading to research in reduction of vascular permeability with mast cell stabilizers or anti-histamine drugs. An animal model studies found that a tryptase inhibitor, nafamostat, or leukotriene inhibitor, montelukast, could reduce the plasma leakage.
In 2018, an open-label study found that patients with montelukast had a 22% absolute risk reduction in dengue shock syndrome, compared to standard treatment. However, there has never been any randomized controlled trial evaluating the efficacy of montelukast in dengue patients.
This study aims to determine the efficacy of montelukast in reducing the incidence of dengue warning signs in adult dengue patients.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Montelukast
a 10 mg tablet will be given orally immediately and every day thereafter for 10 days or until recovery, defined as the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
Montelukast
A 10-mg tablet will be given orally immediately and every day thereafter for 10 days or until recovery, defined as the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
Placebo
a 10 mg tablet will be given orally immediately and every day thereafter for 10 days or until recovery, defined as the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
Placebo
A 10-mg tablet will be given orally immediately and every day thereafter for 10 days or until recovery, defined as the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Montelukast
A 10-mg tablet will be given orally immediately and every day thereafter for 10 days or until recovery, defined as the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
Placebo
A 10-mg tablet will be given orally immediately and every day thereafter for 10 days or until recovery, defined as the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* diagnosis of dengue
* positive NS1 antigen or polymerase chain reaction (PCR) test
Exclusion Criteria
* concurrent diagnosis of other causes of fever, such as malaria or heat stroke
* pregnancy
* being unable to take medication by mouth
* critical illness needing intubation or admission to an intensive care unit
* being unable to communicate
* other indication of montelukast
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Phramongkutklao College of Medicine and Hospital
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Worapong Nasomsong, MD
Role: PRINCIPAL_INVESTIGATOR
Phramongkutklao College of Medicine and Hospital
Worayon Chuerboonchai, MD
Role: PRINCIPAL_INVESTIGATOR
Ananda Mahidol Hospital
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Hatyai Hospital
Hat Yai, Changwat Songkhla, Thailand
Phramongkutklao Hospital
Bangkok, , Thailand
Ananda Mahidol Hospital
Lopburi, , Thailand
Fort Suranari Hospital
Nakhon Ratchasima, , Thailand
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Related Links
Access external resources that provide additional context or updates about the study.
Ahmad A, Waseem T, Butt N, Randhawa F, Malik U, Shakoori T. Montelukast Reduces the Risk of Dengue Shock Syndrome in Dengue Patients. Tropical biomedicine. 2019;35:1115-22.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
AMEDDengue2020
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.