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Pragmatic RCT of High-dose Oral Montelukast for Moderate and Severe Pediatric Acute Asthma Exacerbations

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ClinicalTrials.gov Identifier: NCT03277170
Recruitment Status : Not yet recruiting
First Posted : September 8, 2017
Last Update Posted : April 5, 2018
Sponsor:
Information provided by (Responsible Party):
Donald H Arnold, Vanderbilt University Medical Center

Brief Summary:

Objective: To determine the extent to which high-dose (30mg) oral montelukast, added to standard treatment in children with moderate and severe acute exacerbations improves outcomes.

Central Hypothesis: High-dose oral montelukast, added to standard treatment in children aged 5 to 17 years with moderate and severe acute asthma exacerbations, rapidly improves lung function, clinical severity, hospitalization rate and 72-hour symptom burden.

Secondary Hypotheses:

  1. There are greater effects of high-dose oral montelukast on lung function and on the secondary outcomes in the presence of respiratory viral detection or leukotriene-mediated inflammation; and
  2. There is an interaction between viral detection and urinary leukotriene 4 level with treatment-response.

Design: A two-arm, parallel randomized controlled trial of high-dose oral montelukast versus identical placebo, as add-on to standard treatment of systemic corticosteroid (SCS) and inhaled short-acting Beta-2-agonist (SABA), in children aged 5 to 17 years with moderate and severe acute asthma exacerbations.

Intervention: High-dose oral montelukast added to standard treatment as one treatment-allocation arm, in comparison with standard treatment as the 2nd treatment-allocation arm.

Primary and Important Secondary Endpoints: For the Primary Aim, the primary outcome measure to be compared between arms will be change of %-predicted airway resistance by impulse oscillometry (IOS) at 5Hz (%R5) at 2 hours after treatment initiation. Secondary outcomes will include improvement of %-predicted FEV1 (%FEV1), clinical severity measured using the validated Acute Asthma Intensity Research Score (AAIRS), hospitalization rate, and 72 hour symptom burden using the Pediatric Asthma Caregiver Diary (PACD). For the Secondary Aim, the investigators will determine (1) The effects of high-dose oral montelukast on lung function and on our secondary outcomes in the presence of nasal viruses and of greater leukotriene-mediated inflammation; and (2) The degree of interaction between viral detection and urinary leukotriene E4 (LTE4) level with treatment-response.

Laboratory evaluations: The primary outcome (change of %R5) and select secondary outcomes (%FEV1, AAIRS, LTE4) will be measured before and again at 2 hours after treatment initiation. The other secondary outcomes will be measured at the time of hospitalization decision-making by the clinical team (hospitalization rate) or at 72-hours after treatment initiation (PACD).


Condition or disease Intervention/treatment Phase
Asthma; Status Asthma in Children Asthma Acute Asthma Attack Acute Asthma Exacerbation Drug: Montelukast Oral Granules Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 320 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Two-arm, parallel randomized controlled trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Study drug (montelukast granules) and identical control will be prepared by the Vanderbilt Investigational Drug service. Participants will be randomized by computerized program by study biostatistician.
Primary Purpose: Treatment
Official Title: Pragmatic RCT of High-dose Oral Montelukast for Moderate and Severe Pediatric Acute Asthma Exacerbations
Estimated Study Start Date : September 1, 2018
Estimated Primary Completion Date : August 31, 2021
Estimated Study Completion Date : September 5, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma
Drug Information available for: Montelukast

Arm Intervention/treatment
Experimental: High-dose Montelukast Oral Granules
30 mg (high-dose) oral montelukast granules mixed in apple sauce will be administered orally immediately after informed consent and assent are obtained.
Drug: Montelukast Oral Granules
Montelukast granules, 30 mg, mixed with applesauce
Other Name: Singulair

Placebo Comparator: Placebo
Identical placebo mixed in apple sauce will be administered orally immediately after informed consent and assent are obtained.
Drug: Montelukast Oral Granules
Montelukast granules, 30 mg, mixed with applesauce
Other Name: Singulair




Primary Outcome Measures :
  1. Change of percent-predicted airway resistance at 5Hz (%R5) by impulse oscillometry [ Time Frame: Before and 2-hours after treatment with montelukast or placebo ]
    Change of percent-predicted airway resistance at 5Hz (%R5) by impulse oscillometrypost montelukast or control administration


Secondary Outcome Measures :
  1. Change of percent-predicted forced expiratory volume in 1-second (FEV1) [ Time Frame: Before and 2-hours after treatment with montelukast or placebo ]
    Change of percent-predicted forced expiratory volume in 1-second (FEV1)

  2. Change of the Acute Asthma Intensity Research Score (AAIRS) [ Time Frame: Before and 2-hours after treatment with montelukast or placebo ]
    Change of the Acute Asthma Intensity Research Score (AAIRS)

  3. Leukotriene E4 (LTE4) [ Time Frame: Before treatment with montelukast or placebo ]
    Leukotriene E4 (LTE4)

  4. 72-hours symptom burden measured using the pediatric asthma caregiver diary (PACD) [ Time Frame: Before and at 72-hours after treatment with montelukast or placebo ]
    72-hours symptom burden measured using the pediatric asthma caregiver diary (PACD)

  5. Hospitalization rate [ Time Frame: 8-hours after treatment with montelukast or placebo ]
    Hospitalization rate



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Ages Eligible for Study:   5 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Age 5 to 17 years, inclusive
  • Parental report of asthma diagnosis by a health care provider
  • At least one previous wheezing episode treated with albuterol
  • Moderate or severe acute asthma exacerbation measured using the validated AAIRS bedside asthma severity score

Exclusion criteria:

  • Prior study enrollment
  • Chronic lung disease other than asthma
  • History of prematurity less than 34 weeks gestational age
  • Acute or chronic liver disease
  • Presence of tracheostomy
  • Use of noninvasive ventilation at home
  • Need for immediate airway intervention (e.g., endotracheal intubation or noninvasive ventilation)
  • Allergy to montelukast
  • Pregnancy
  • Tuberculosis
  • Gastroesophageal reflux requiring acid-blocking medication; and
  • Prior use of an LTRA (e.g., montelukast)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03277170


Contacts
Contact: Donald H Arnold, MD, MPH 615-936-4898 don.arnold@vanderbilt.edu

Locations
United States, Tennessee
Vanderbilt Children's Hospital
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University Medical Center
Investigators
Principal Investigator: Donald H Arnold, MD, MPH Vanderbilt University School of Medicine, Department of Pediatrics

Publications of Results:
Responsible Party: Donald H Arnold, Professor of Pediatrics and Emergency Medicine, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT03277170     History of Changes
Other Study ID Numbers: 000
First Posted: September 8, 2017    Key Record Dates
Last Update Posted: April 5, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: This plan is to be developed in concert with our IRB.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Donald H Arnold, Vanderbilt University Medical Center:
acute asthma exacerbation
pediatric asthma
leukotriene receptor antagonist
montelukast

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Montelukast
Anti-Asthmatic Agents
Respiratory System Agents
Leukotriene Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP1A2 Inducers
Cytochrome P-450 Enzyme Inducers
Molecular Mechanisms of Pharmacological Action