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

Primary Purpose

Dengue, Dengue With Warning Signs, Dengue Shock Syndrome

Status
Completed
Phase
Phase 2
Locations
Thailand
Study Type
Interventional
Intervention
Montelukast
Placebo
Sponsored by
Phramongkutklao College of Medicine and Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dengue

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hatyai Hospital
  • Phramongkutklao Hospital
  • Ananda Mahidol Hospital
  • Fort Suranari Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Montelukast

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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 However, lethargy will be excluded as a criterion for warning sign as almost all patients reported subjective lethargy.

Secondary Outcome Measures

Rate of each component of composite outcome of dengue with warning signs
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
Rate of hospitalization
Rate of admission to hospital
Length of hospital stay
Length of hospital stay
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
Rate of dengue shock
Rate of hypotension or the pulse pressure of ≤ 20 mm Hg
30-day mortality
death with in 30 days

Full Information

First Posted
December 9, 2020
Last Updated
July 17, 2023
Sponsor
Phramongkutklao College of Medicine and Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04673422
Brief Title
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

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
January 15, 2021 (Actual)
Primary Completion Date
June 17, 2023 (Actual)
Study Completion Date
June 17, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Phramongkutklao College of Medicine and Hospital

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dengue, Dengue With Warning Signs, Dengue Shock Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
a randomized, prospective, 2-arm, parallel-group, double-blind, placebo-controlled superiority trial
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
358 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Montelukast
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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
Intervention Name(s)
Montelukast
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
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
Primary Outcome Measure Information:
Title
Rate of dengue with warning signs
Description
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.
Time Frame
14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter.
Secondary Outcome Measure Information:
Title
Rate of each component of composite outcome of dengue with warning signs
Description
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
Time Frame
14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
Title
Rate of hospitalization
Description
Rate of admission to hospital
Time Frame
14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
Title
Length of hospital stay
Description
Length of hospital stay
Time Frame
up to 90 days
Title
Rate of severe dengue
Description
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
Time Frame
14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
Title
Rate of dengue shock
Description
Rate of hypotension or the pulse pressure of ≤ 20 mm Hg
Time Frame
14 days or until the discontinuation of the follow up appointment by the attending physicians, whichever is shorter
Title
30-day mortality
Description
death with in 30 days
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Worapong Nasomsong, MD
Organizational Affiliation
Phramongkutklao College of Medicine and Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Worayon Chuerboonchai, MD
Organizational Affiliation
Ananda Mahidol Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hatyai Hospital
City
Hat Yai
State/Province
Songkhla
Country
Thailand
Facility Name
Phramongkutklao Hospital
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Facility Name
Ananda Mahidol Hospital
City
Lopburi
ZIP/Postal Code
15000
Country
Thailand
Facility Name
Fort Suranari Hospital
City
Nakhon Ratchasima
ZIP/Postal Code
30000
Country
Thailand

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
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Links:
URL
https://msptm.org/files/Vol35No4/1115-1122-Tania-Shakoori.pdf
Description
Ahmad A, Waseem T, Butt N, Randhawa F, Malik U, Shakoori T. Montelukast Reduces the Risk of Dengue Shock Syndrome in Dengue Patients. Tropical biomedicine. 2019;35:1115-22.

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

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