Two Doses of the Intravenous Magnesium Sulfate Versus the Standard Single Dose ,With/ Without the Nebulized Budesonide For the Management of the Severe Asthma Exacerbation in the Emergency Room; A Randomized Controlled Trial.

Study Overview
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Brief Summary
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Many studies have investigated the efficacy and safety of Intravenous magnesium sulfate and inhaled steroids in addition to the standard treatment for patients with severe asthma attacks. In this 2x2 factorial design blinded randomized study, no interaction of hypothesized treatments is expected.Investigators hypothesize that two doses of intravenous magnesium sulfate,a high dose followed by a (lower) standard dose, will shorten the time to medical readiness for discharge compared to a single standard dose followed by placebo.The second hypothesis is that nebulized inhaled budesonide will be superior to placebo.

Detailed Description
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Patient with a severe asthma attack will be admitted to the observation area in the Pediatric Emergency Center and assessed for eligibility for the study by the attending physician, based upon our study inclusion/exclusion criteria. Eligible patients will be enrolled after obtaining written consent from the parents. Patients will receive routine treatment for a severe asthma attack, such as inhaled bronchodilators, plus intravenous steroids and supplementary oxygen if needed. Standard blood work and chest X-Ray will be obtained and bronchial asthma severity score will be measured at baseline before starting treatment,and then at 4,8,12,24,36,48 hr and thereafter. The medical team as well as parents and patient will be blinded to the medications delivered. The patient will be randomized into one of the four study groups and adverse effects of the medications in each group will be monitored and documented carefully.

Official Title
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Two Doses of the Intravenous Magnesium Sulfate Versus the Standard Single Dose With/Without Nebulized Budesonide for the Emergency Management of the Severe Asthma. A Randomized Controlled Trial.

Conditions
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Bronchial Asthma

Intervention / Treatment
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* Drug: Hi-dose iv MgSO4
* Drug: Nebulized budesonide
* Drug: Std-dose iv MgSO4
* Drug: Nebulized normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children 2-14 years of age. Known to have bronchial asthma. Presenting in severe asthma exacerbation Asthma severity score 8 or higher according to PRAM asthma severity . Exclusion Criteria: Prematurity <34 weeks of gestation. Critically ill children requiring immediate intubation or ICU admission. Transfers from other institutions. Adverse drug reaction or allergy to budesonide,salbutamol,ipratropium bromide, prednisone, prednisolone, methylprednisolone, or magnesium sulfate. History of neuromuscular disease, cardiac disease, renal disease, liver disease. Underlying chronic lung disease. Radiographic evidence of pneumonia or lung collapse . Hemodynamic instability. Instrumented airway or Tracheotomy. Colostomy or ileostomy. Malabsorption disorder. Known vitamin D deficiency. Receiving Milk of Magnesium for Constipation Chronic diarrhea (duration for 2 weeks) Diuretics use. Immunodeficiency.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hi-Mg + Bud<br>Group one will receive a high,then standard dose of intravenous magnesium sulfate with blinded nebulized budesonide. | Drug: Hi-dose iv MgSO4<br> <br> Drug: Nebulized budesonide<br> <br> * Other names: Pulmicort;|
| Placebo Comparator: Hi-Mg + P<br>Group two will receive a high,then standard dose of intravenous magnesium sulfate with blinded nebulized normal saline. | Drug: Hi-dose iv MgSO4<br> <br> Drug: Nebulized normal saline<br> <br> |
| Active Comparator: Std-Mg + Bud<br>Group three will receive a single standard dose of intravenous magnesium sulfate plus one dose of intravenous normal saline with blinded nebulized budesonide. | Drug: Nebulized budesonide<br> <br> * Other names: Pulmicort;Drug: Std-dose iv MgSO4<br> <br> |
| Placebo Comparator: St-Mg + P<br>Group four will receive a single dose of intravenous magnesium sulfate plus one dose of intravenous normal saline with blinded nebulized normal saline | Drug: Std-dose iv MgSO4<br> <br> Drug: Nebulized normal saline<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to medical readiness for discharge. | Accelerated failure time analyses of each of the blinded interventions will use the entire population,as this is a 2x2 factorial study.We will use retrospective stratification & quantitative interaction analysis to determine if the magnesium or magnesium placebo intervention has a different effect in the budesonide or budesonide placebo group. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall length of the hospital stay (hours/days) . |  | 3 years | 
| The rate of admission to pediatric intensive care unit (%) |  | 3 years | 
| Comparison of clinical response in severity score (%) |  | 3 years | 
| Frequency of need for revisit to pediatric emergency center for same diagnosis(%) |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bronchial Asthma, Intravenous magnesium sulfate, Inhaled budesonide