Clinical trial NCT06747130: Efficacy of Montelukast in Preventing Transaminase Elevation in Adult Dengue Patients
Official title: Efficacy of Montelukast in Preventing Transaminase Elevation in Adult Dengue Patients: a Randomized, Double-blind, Placebo Controlled, Superiority Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Dengue
Montelukast
Transaminases
Lead sponsor: Phramongkutklao College of Medicine and Hospital
Sponsor class: OTHER
First posted: 2024-12-24
Enrollment: 82
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Serum transaminase levels on the recovery day
timeFrame: From enrollment to the end of treatment at 10 days
Secondary outcomes:
measure: Proportion of subjects with abnormal serum transaminase levels on the recovery day
timeFrame: From enrollment to the end of treatment at 10 days
measure: Length of stay
timeFrame: From enrollment to the end of treatment at 10 days
measure: Changes in serum transaminase levels
timeFrame: From enrollment to the end of treatment at 10 days
measure: Rate of dengue with warning signs
timeFrame: From enrollment to the end of treatment at 10 days
measure: Rate of severe dengue
timeFrame: From enrollment to the end of treatment at 10 days
measure: Rate of dengue shock
timeFrame: From enrollment to the end of treatment at 10 days
measure: Hematocrit and platelet
timeFrame: From enrollment to the end of treatment at 10 days
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Phramongkutklao Hospital
Study officials:
affiliation: Phramongkutklao College of Medicine and Hospital
name: Worapong Nasomsong, MD
role: STUDY_DIRECTOR
References: