Effect of Montelukast in Preventing Dengue With Warning Signs in Dengue Patients

July 17, 2023 updated by: Phramongkutklao College of Medicine and Hospital

Effect of Montelukast in Preventing Dengue With Warning Signs in Dengue Patients: a Multicenter Randomized, Double-blind, Placebo Controlled, Superiority Trial

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

358

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Vasin Vasikasin, MD
  • Phone Number: 93337 (+66) 2763-9300
  • Email: vvasin@gmail.com

Study Contact Backup

Study Locations

  • Thailand
      • Bangkok, Thailand, 10400
        • Phramongkutklao Hospital
      • Lopburi, Thailand, 15000
        • Ananda Mahidol Hospital
      • Nakhon Ratchasima, Thailand, 30000
        • Fort Suranari Hospital
    • Songkhla
      • Hat Yai, Songkhla, Thailand
        • Hatyai Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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: 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
Rate of dengue with warning signs
Time Frame: 14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter.

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 However, lethargy will be excluded as a criterion for warning sign as almost all patients reported subjective lethargy.
14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of each component of composite outcome of dengue with warning signs
Time Frame: 14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter

Rate of each component of composite outcome of dengue with warning signs

  • abdominal tenderness or pain
  • persistent vomiting
  • clinical fluid accumulation
  • mucosal bleeding
  • liver enlargement >2cm
  • increase in hematocrit concurrent with decrease in platelet count
14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
Rate of hospitalization
Time Frame: 14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
Rate of admission to hospital
14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
Length of hospital stay
Time Frame: up to 90 days
Length of hospital stay
up to 90 days
Rate of severe dengue
Time Frame: 14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter

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
14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
Rate of dengue shock
Time Frame: 14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
Rate of hypotension or the pulse pressure of ≤ 20 mm Hg
14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
30-day mortality
Time Frame: 30 days
death with in 30 days
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Phramongkutklao College of Medicine and Hospital

Investigators

  • Principal Investigator: Worapong Nasomsong, MD, Phramongkutklao College of Medicine and Hospital
  • Principal Investigator: Worayon Chuerboonchai, MD, Ananda Mahidol Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 15, 2021

Primary Completion (Actual)

June 17, 2023

Study Completion (Actual)

June 17, 2023

Study Registration Dates

First Submitted

December 9, 2020

First Submitted That Met QC Criteria

December 15, 2020

First Posted (Actual)

December 17, 2020

Study Record Updates

Last Update Posted (Actual)

July 18, 2023

Last Update Submitted That Met QC Criteria

July 17, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AMEDDengue2020

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data requests can be made anytime from 6 months after the publication of this trial. De-identified participant data can be requested by researchers for use in independent scientific research and will be provided following review and approval of the research proposal (including statistical analysis plan).

IPD Sharing Time Frame

starting 6 months after publication

IPD Sharing Access Criteria

De-identified participant data can be requested by researchers for use in independent scientific research and will be provided following review and approval of the research proposal (including statistical analysis plan). Requests should be sent to the corresponding author after publication.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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