Inhaled Magnesium in Refractory Pediatric Acute Asthma

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by The Hospital for Sick Children
Sponsor:
Information provided by (Responsible Party):
Suzanne Schuh, The Hospital for Sick Children
ClinicalTrials.gov Identifier:
NCT01429415
First received: September 2, 2011
Last updated: December 6, 2013
Last verified: December 2013
  Purpose

Acute asthma is the most common cause of pediatric hospitalizations. While the investigators know that repeat inhalations of ß2 agonists and ipratropium with early oral steroids substantially reduce hospitalizations, many children are resistant to this standard initial therapy. About a third of children remaining in moderate to severe distress after standard therapy are admitted to hospital and comprise 84% of pediatric acute asthma hospitalizations. Finding safe, non-invasive, and effective strategies to treat children resistant to standard therapy would substantially decrease hospitalizations resulting in considerable health care savings and reduction of the psycho-social burden of the disease. While studies of magnesium sulfate (Mg) given intravenously (IV) suggest that this agent can reduce hospitalizations in both adults and children resistant to standard initial therapy Nebulization is an alternate route for administering Mg. This route has the advantage of being non-invasive and is likely much safer due to lower systemic delivery. Direct delivery via nebulization allows higher Mg concentrations at the target site, the lower airways, with a smaller total drug dose. The investigators propose to conduct a properly designed study to clarify the role of nebulized Mg.


Condition Intervention Phase
Acute Asthma
Drug: Inhaled Magnesium Sulfate
Drug: Hypertonic Saline Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Inhaled Magnesium in Refractory Pediatric Acute Asthma

Resource links provided by NLM:


Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:
  • Hospitalization of Subject [ Time Frame: Up to 24 hours after treatment ] [ Designated as safety issue: No ]
    Defined as admission to an inpatient unit within 24hours of the start of experimental therapy due to continued/worsening distress.


Secondary Outcome Measures:
  • Pediatric Respiratory Assessment Measure (PRAM) [ Time Frame: 0, 20, 40 60, 120, 180, 240 minutes post dose ] [ Designated as safety issue: No ]
  • Changes in Vitals [ Time Frame: 0, 20, 40, 60, 120, 180, 240 minutes post dose ] [ Designated as safety issue: No ]
    Respiratory Rate, O2 saturation, Blood pressure

  • Number of Salbutamol Treatments [ Time Frame: Up to 240 minutes post dose ] [ Designated as safety issue: No ]
  • Medical History and Phenotype [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The investigators will measure hospitalization and age, gender, pre-randomization PRAM score, personal history of atopy, and "acute viral induced wheeze" phenotype. This phenotype will be defined by age less than 5 years, co-existent upper respiratory tract infection, no interval symptoms between exacerbations, no atopy


Estimated Enrollment: 816
Study Start Date: September 2011
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental Group
inhaled Mg sulfate 600 mg plus salbutamol 5 mg via Pockethaler nebulizer q 20 minutes x3 treatments
Drug: Inhaled Magnesium Sulfate
Each treatment will utilize 600 mg (1.2 mL) of Mg sulfate
Placebo Comparator: Control Group
inhaled placebo plus salbutamol 5 mg via Pockethaler nebulizer q 20 minutes x3 treatments
Drug: Hypertonic Saline Placebo
The control group will receive 1.2 mL hypertonic 5.5% saline (to match osmolarity of Mg sulfate)

Detailed Description:

The investigators plan the following specific aims:

  1. Primary Objective: To examine if in children with acute asthma remaining in moderate to severe respiratory distress despite maximized initial bronchodilator and steroid therapy there is a reduction in hospitalization rate from the ED in those who receive nebulized Mg with salbutamol versus those receiving salbutamol only.

    Hypothesis: The investigators hypothesize that the children with Pediatric Respiratory Assessment Measure (PRAM) ≥ 5 points after optimized initial inhaled bronchodilator and oral steroid therapies who are given nebulized Mg in addition to nebulized salbutamol will have significantly lower hospitalization rate within 24 hours of starting the study compared to those given salbutamol only.

  2. To compare a difference in the changes in the validated Pediatric Respiratory Assessment Measure (PRAM), respiratory rate, oxygen saturation and blood pressure from randomization baseline to 240 minutes in the two groups
  3. To determine if there is a significant association between the difference in the primary outcome between the groups and the patient's age, gender, baseline PRAM score, personal history of atopy and "viral-induced wheeze" phenotype.

Hypothesis(es) to be Tested In this randomized, double-blind two-centre trial, the investigators hypothesize that children with acute asthma with a Pediatric Respiratory Assessment Measure (PRAM) of ≥ 5 points after optimized initial inhaled bronchodilator and oral steroid therapies who are given nebulized Mg in addition to nebulized salbutamol will have at least a 15% lower hospitalization rate within 24 hours of starting the study as compared to those given salbutamol only.

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 2-17 years of age
  2. Diagnosis of asthma, defined as this diagnosis made by a physician and at least one prior acute episode of wheezing with cough or dyspnea treated with inhaled ß2 agonists or oral corticosteroids. Our study population will exclude bronchiolitis and first-time wheeze (potential alternate diagnoses).
  3. Persistent moderate to severe airway obstruction after 3 doses of salbutamol and ipratropium, defined as a PRAM 5 or higher. A PRAM score of 5 or more following initial therapy indicates the child has at least moderate disease severity37 and has a high likelihood of being hospitalized.37 This group of children includes 84% of all pediatric asthma hospitalizations; therefore, finding an effective therapy for this population has great potential to significantly reduce hospitalizations. (Appendix B).

Exclusion Criteria:

  1. No previous history of wheezing or bronchodilator therapy. Some children who present with wheezing for the first time will have other diagnoses which would not be expected to respond to Mg.
  2. Patients who have already received IV Mg therapy during the index visit.
  3. Critically ill children requiring immediate intubation. These children need immediate ICU management and hospitalization.
  4. Children who in the opinion of the treating physician require a chest radiograph due to atypical clinical presentation and are found to have radiologist-confirmed pneumonia. These rare patients may have to be hospitalized primarily for treatment of the infection and may not respond to magnesium.
  5. Known co-existent renal, chronic pulmonary, neurologic, cardiac or systemic disease. These conditions may influence the response to Mg and hospitalization.
  6. Transfers from other institutions. These patients would have received initial therapy well before arrival, potentially represent a different stage of their acute disease and may respond differently to Mg therapy.
  7. Known hypersensitivity to Mg sulfate.
  8. Patients previously enrolled in the study.
  9. Insufficient command of the English language.
  10. Lack of a home or cellular telephone.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01429415

Contacts
Contact: Suzanne Schuh, MD 416-813-6239 suzanne.schuh@sickkids.ca
Contact: Caseita Dewar 413-813-7654 ext 1486 caseita.dewar@sickkids.ca

Locations
Canada, Alberta
Alberta Children's Hospital Active, not recruiting
Calgary, Alberta, Canada, T3B 6A8
Canada, Ontario
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5V1X8
Contact: Suzanne Schuh, M.D.    4160813-6239    suzanne.schuh@sickkids.ca   
Principal Investigator: Suzanne Schuh, M.D.         
Sponsors and Collaborators
The Hospital for Sick Children
Investigators
Principal Investigator: Suzanne Schuh, MD The Hospital for Sick Children
  More Information

No publications provided

Responsible Party: Suzanne Schuh, Staff Physician, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT01429415     History of Changes
Other Study ID Numbers: 1000024908
Study First Received: September 2, 2011
Last Updated: December 6, 2013
Health Authority: Canada: Health Canada

Keywords provided by The Hospital for Sick Children:
pediatric
Acute Asthma
Inhaled Magnesium

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Magnesium Sulfate
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anesthetics
Central Nervous System Depressants
Anti-Arrhythmia Agents
Cardiovascular Agents
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Tocolytic Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on July 20, 2014