Efficacy of Montelukast in Preventing Transaminase Elevation in Adult Dengue Patients

Efficacy of Montelukast in Preventing Transaminase Elevation in Adult Dengue Patients: a Randomized, Double-blind, Placebo Controlled, Superiority Trial

The goal of this clinical trial is to learn if drug montelukast works to treat dengue in adults. It will also learn about the safety of drug montelukast . The main questions it aims to answer are:

Does drug montelukast lower the incidence of liver enzyme elevations in participants ? What medical problems do participants have when taking drug montelukast ?

Study Overview

• Status: Recruiting
• Conditions: Dengue; Montelukast; Transaminases
• Intervention / Treatment: Drug: Montelukast; Drug: Montelukast Placebo

Detailed Description

Dengue remains a significant and growing public health issue in many tropical countries, with almost 4 billion people estimated to be at risk worldwide and an annual incidence of approximately 400 million infections. In 2019 alone, 5.2 million cases of dengue were reported globally.

In addition to its acute clinical manifestations, dengue is a leading cause of liver failure in tropical regions. Elevated concentrations of transaminases have been strongly correlated with disease severity. Severe acute hepatitis in dengue patients is associated with prolonged hospital stays, increased mortality, bleeding complications, and renal failure. While transaminase elevations are commonly linked to shock and subsequent ischemic hepatitis, studies indicate that these elevations often precede the onset of shock by several days. Notably, elevated transaminase levels during the febrile stage have been predictive of subsequent shock, underscoring their potential role as an early marker of disease progression.

Leukotrienes play a pivotal role in the pathophysiology of dengue by promoting plasma leakage and leukocyte adhesion within postcapillary venules. In dengue patients, leukotriene levels are markedly elevated-up to 35-38 times baseline levels-during the febrile and defervescence stages, returning to normal during the convalescent phase. Animal model studies have demonstrated that leukotriene blockade significantly reduces plasma leakage, suggesting its potential as a therapeutic target.

Currently, the management of dengue is limited to symptomatic treatment and intravenous fluid replacement, with no specific interventions proven to prevent complications. Preclinical studies have identified nafamostat, a tryptase inhibitor, and montelukast, a leukotriene receptor antagonist, as promising agents for reducing plasma leakage. An open-label clinical study in 2018 reported a 22% absolute risk reduction in dengue shock syndrome among patients treated with montelukast compared to standard care. However, a subsequent randomized controlled trial in 2024 failed to demonstrate efficacy of montelukast in preventing plasma leakage or warning signs of severe dengue. This discrepancy may reflect either the ineffectiveness of montelukast or the low incidence of warning signs in the trial population. Interestingly, secondary analyses revealed that participants in the montelukast group had a lower incidence of transaminase elevations compared to those receiving placebo, suggesting a potential hepatoprotective effect.

This study aims to evaluate the efficacy of montelukast in reducing the incidence of transaminase elevations in adult patients with dengue.

• Study Type: Interventional
• Enrollment (Estimated): 82
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Vasin Vasikasin, MD PhD; Phone Number: 93337 66+027639300; Email: vvasin@gmail.com
• Study Contact Backup: Name: Kotchaphon Waithayakul, MD; Phone Number: 93278 66+027639300; Email: nasomsong.w@gmail.com

Study Locations

• Thailand
  • Bangkok, Thailand, 10400
    • Recruiting
    • Phramongkutklao Hospital
    • Contact: Worapong Nasomsong, MD; Phone Number: 93337 6627639300; Email: nasomsong.w@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient age >18 years
• Dengue infection diagnosed by NS1 antigen, or polymerase chain reaction
• Admitted to the hospital
• Written informed consent from patient or attending relative able to and willing to give informed consent

Exclusion Criteria:

• Other possible cause of fever other than dengue infection
• Pregnancy
• Unable to take medication
• Aminotransferase level above 150 U/l
• Allergy to paracetamol or tramadol
• Paracetamol indicated for condition other than dengue infection
• Critically ill patient who need ICU or invasive ventilation support
• History of cirrhosis
• Unable to communicate
• Other indication of montelukast
• History of psychiatric illness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: 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 Comparator: 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	Drug: Montelukast 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum transaminase levels on the recovery day	Serum alanine transaminase and aspartate transaminase level will be measured at admission, and on every morning afterwards until the subject is discharged. The proportion of subjects with abnormal serum transaminase levels will be compared. The recovery day is defined as the day the participant was discharged from the hospital.	From enrollment to the end of treatment at 10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with abnormal serum transaminase levels on the recovery day	Serum alanine transaminase and aspartate transaminase level will be measured at admission, and on every morning afterwards until the subject is discharged. The proportion of subjects with abnormal serum transaminase levels will be compared.	From enrollment to the end of treatment at 10 days
Length of stay	Duration from hospital admission to discharge will be compared.	From enrollment to the end of treatment at 10 days
Changes in serum transaminase levels	The change in serum transaminase levels from baseline at admission will be compared.	From enrollment to the end of treatment at 10 days
Rate of dengue with warning signs	Rate of a composite outcome including abdominal tenderness or pain, persistent vomiting, clinical fluid accumulation, mucosal bleeding, liver enlargement >2cm, increase in hematocrit concurrent with decrease in platelet count	From enrollment to the end of treatment at 10 days
Rate of severe dengue	Rate of a composite outcome including shock, fluid accumulation with respiratory distress, severe bleeding leading to hypotension or decreased hematocrit, liver transaminase >1000, impaired consciousness, heart and other organ failure	From enrollment to the end of treatment at 10 days
Rate of dengue shock	Rate of hypotension or the pulse pressure of ≤ 20 mm Hg	From enrollment to the end of treatment at 10 days
Hematocrit and platelet	Hematocrit and platelet levels will be compared.	From enrollment to the end of treatment at 10 days

Collaborators and Investigators

• Sponsor: Phramongkutklao College of Medicine and Hospital
• Investigators: Study Director: Worapong Nasomsong, MD, Phramongkutklao College of Medicine and Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: December 18, 2024
• First Submitted That Met QC Criteria: December 18, 2024
• First Posted (Actual): December 24, 2024

Study Record Updates

• Last Update Posted (Actual): May 29, 2025
• Last Update Submitted That Met QC Criteria: May 27, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; RNA Virus Infections; Virus Diseases; Arbovirus Infections; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Dengue; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Respiratory System Agents; Anti-Asthmatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP1A2 Inducers; Leukotriene Antagonists; Montelukast
• Other Study ID Numbers: R165h/67

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No