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

September 2, 2011
December 6, 2013
September 2011
December 2017   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01429415 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
Inhaled Magnesium in Refractory Pediatric Acute Asthma
Inhaled Magnesium in Refractory Pediatric Acute Asthma

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Acute Asthma
  • Drug: Inhaled Magnesium Sulfate
    Each treatment will utilize 600 mg (1.2 mL) of Mg sulfate
  • Drug: Hypertonic Saline Placebo
    The control group will receive 1.2 mL hypertonic 5.5% saline (to match osmolarity of Mg sulfate)
  • Experimental: Experimental Group
    inhaled Mg sulfate 600 mg plus salbutamol 5 mg via Pockethaler nebulizer q 20 minutes x3 treatments
    Intervention: Drug: Inhaled Magnesium Sulfate
  • Placebo Comparator: Control Group
    inhaled placebo plus salbutamol 5 mg via Pockethaler nebulizer q 20 minutes x3 treatments
    Intervention: Drug: Hypertonic Saline Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
816
December 2017
December 2017   (final data collection date for primary outcome measure)

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.
Both
2 Years to 17 Years
No
Contact: Suzanne Schuh, MD 416-813-6239 suzanne.schuh@sickkids.ca
Contact: Caseita Dewar 413-813-7654 ext 1486 caseita.dewar@sickkids.ca
Canada
 
NCT01429415
1000024908
No
Suzanne Schuh, The Hospital for Sick Children
The Hospital for Sick Children
Not Provided
Principal Investigator: Suzanne Schuh, MD The Hospital for Sick Children
The Hospital for Sick Children
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP