Efficacy of Montelukast in Preventing Transaminase Elevation in Adult Dengue Patients

NCT ID: NCT06747130

Last Updated: 2025-05-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-31
• Study Completion Date: 2027-01-31

Brief Summary

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 ?

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.

Conditions

Dengue; Montelukast; Transaminases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: EXPERIMENTAL

Montelukast

Intervention Type: DRUG

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

Group Type: PLACEBO_COMPARATOR

Montelukast Placebo

Intervention Type: DRUG

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

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

Intervention Type: 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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Phramongkutklao College of Medicine and Hospital

OTHER

Sponsor Role: lead

Responsible Party

Vasin Vasikasin

Assistant Professor, Consultant in Infectious Disease

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Worapong Nasomsong, MD

Role: STUDY_DIRECTOR

Phramongkutklao College of Medicine and Hospital

Locations

Phramongkutklao Hospital

Bangkok, , Thailand

Site Status: RECRUITING

Countries

Thailand

Central Contacts

Vasin Vasikasin, MD PhD

Role: CONTACT

vvasin@gmail.com

66+027639300 ext. 93337

Kotchaphon Waithayakul, MD

Role: CONTACT

nasomsong.w@gmail.com

66+027639300 ext. 93278

Facility Contacts

Worapong Nasomsong, MD

Role: primary

nasomsong.w@gmail.com

6627639300 ext. 93337

Other Identifiers

R165h/67

Identifier Type: -

Identifier Source: org_study_id