Clinical trial NCT04673422: Effect of Montelukast in Preventing Dengue With Warning Signs in Dengue Patients
Official title: Effect of Montelukast in Preventing Dengue With Warning Signs in Dengue Patients: a Multicenter Randomized, Double-blind, Placebo Controlled, Superiority Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Dengue
Dengue With Warning Signs
Dengue Shock Syndrome
Lead sponsor: Phramongkutklao College of Medicine and Hospital
Sponsor class: OTHER
First posted: 2020-12-17
Enrollment: 358
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: a randomized, prospective, 2-arm, parallel-group, double-blind, placebo-controlled superiority trial
Primary purpose: TREATMENT

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

Detailed description: Dengue has been the growing public health problem in many tropical countries. Almost 4 billion people were estimated to be at risk, with estimated 400 million infections occurring annually. In Asia, around 10% of febrile patients were virologically confirmed with dengue. The most common cause of death is from dengue shock as a result of vascular leak syndrome. This condition can occur in various clinical manifestations ranging from mild cases to life-threatening condition of dengue shock syndrome. The common sites of plasma leakage are pleural effusion and ascites. The contributing factors for endothelial dysfunction in dengue are cytokines such as soluble tumor necrosis factor receptor (sTNFR/75), interferon gamma, and vascular endothelial growth factor, NS1 antigenemia, complement activation, and activation of dendritic cells, macrophages, and mast cells.

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.

Eligibility criteria: Inclusion Criteria:

* at least 18 years old
* diagnosis of dengue
* positive NS1 antigen or polymerase chain reaction (PCR) test

Exclusion Criteria:

* any warning sign of dengue
* 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

Primary outcomes:
measure: Rate of dengue with warning signs
timeFrame: 14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter.
Secondary outcomes:
measure: Rate of each component of composite outcome of dengue with warning signs
timeFrame: 14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
measure: Rate of hospitalization
timeFrame: 14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
measure: Length of hospital stay
timeFrame: up to 90 days
measure: Rate of severe dengue
timeFrame: 14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
measure: Rate of dengue shock
timeFrame: 14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
measure: 30-day mortality
timeFrame: 30 days
Other outcomes:
Locations:
city: Hat Yai
country: Thailand
facility: Hatyai Hospital
state: Songkhla
city: Bangkok
country: Thailand
facility: Phramongkutklao Hospital
city: Lopburi
country: Thailand
facility: Ananda Mahidol Hospital
city: Nakhon Ratchasima
country: Thailand
facility: Fort Suranari Hospital
Study officials:
affiliation: Phramongkutklao College of Medicine and Hospital
name: Worapong Nasomsong, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ananda Mahidol Hospital
name: Worayon Chuerboonchai, MD
role: PRINCIPAL_INVESTIGATOR
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