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Magnesium Nebulization Utilization in Management of Pediatric Asthma (MAGNUMPA)

Primary Purpose

Acute Asthma

Status

Completed

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Magnesium Sulfate Sandoz

Sodium Chloride , USP PPC

About this trial

This is an interventional treatment trial for Acute Asthma focused on measuring pediatric, Acute Asthma, Inhaled Magnesium

Eligibility Criteria

2 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

2-17 years of age
Diagnosis of asthma/reactive airways/viral wheeze, 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).
Persistent moderate to severe airway obstruction after 3 doses of salbutamol and ipratropium (as per site specific standard of care guidelines) -, 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 severity and has a high likelihood of being hospitalized.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:

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.
Patients who have already received IV Mg therapy during the index visit.
Critically ill children requiring immediate intubation. These children need immediate ICU management and hospitalization.
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.
Known co-existent renal, chronic pulmonary, neurologic, cardiac or systemic disease. These conditions may influence the response to Mg and hospitalization.
Known hypersensitivity to Mg sulfate.
Patients previously enrolled in the study.
Insufficient command of the English and or French language.
Lack of a home or cellular telephone.
Known allergy/sensitivity to latex.

Sites / Locations

Alberta Children's Hospital
Stollery Hospital
BC Children's Hospital
The Manitoba Institute of Child Health
Children's Hospital of Eastern Ontario
The Hospital for Sick Children
Ste Justine Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental Group

Control Group

Arm Description

Magnesium Sulfate Sandoz/PPC 600mg and Salbutamol (GlaxoSmithKline/Pharmascience) 5mg by inhalation via Aeroneb Go nebulizer (Philips) with Idehaler Pocket chamber DTF q 20 minutes, 3 treatments.

Sodium Chloride USP PPC/Omega (5.5%) placebo and salbutamol GlaxoSmithKline/Pharmascience 5 mg by inhalation via Aeroneb Go nebulizer Philips with Idehaler Pocket chamber DTF q 20 minutes, 3 treatments.

Outcomes

Primary Outcome Measures

Hospitalization of Subject

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)

PRAM is a validated measure of asthma severity in the Emergency Department

Changes in Vitals

Respiratory Rate, O2 saturation, Blood pressure

Number of Salbutamol Treatments

This measure of additional therapy may strengthen the measure of benefit of inhaled magnesium

Medical History and Phenotype

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

Full Information

NCT ID

NCT01429415

First Posted

September 2, 2011

Last Updated

March 31, 2020

Sponsor

The Hospital for Sick Children

Collaborators

Canadian Institutes of Health Research (CIHR), Alberta Children's Hospital, St. Justine's Hospital, Children's Hospital of Eastern Ontario, Stollery Children's Hospital, The Children's Hospital of Winnipeg, Provincial Health Services Authority

1. Study Identification

Unique Protocol Identification Number

NCT01429415

Brief Title

Magnesium Nebulization Utilization in Management of Pediatric Asthma

Acronym

MAGNUMPA

Official Title

Magnesium Nebulization Utilization in Management of Pediatric Asthma

Study Type

Interventional

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Completed

Study Start Date

September 26, 2011 (Actual)

Primary Completion Date

November 19, 2019 (Actual)

Study Completion Date

November 22, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The Hospital for Sick Children

Collaborators

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

Detailed Description

The investigators plan the following specific aims: 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. 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 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 seven-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 10% lower hospitalization rate within 24 hours of starting the study as compared to those given salbutamol only.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Asthma

Keywords

pediatric, Acute Asthma, Inhaled Magnesium

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

818 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Experimental Group

Arm Type

Experimental

Arm Description

Magnesium Sulfate Sandoz/PPC 600mg and Salbutamol (GlaxoSmithKline/Pharmascience) 5mg by inhalation via Aeroneb Go nebulizer (Philips) with Idehaler Pocket chamber DTF q 20 minutes, 3 treatments.

Arm Title

Control Group

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Magnesium Sulfate Sandoz

Other Intervention Name(s)

Magnesium Sulfate, USP 50% PPC

Intervention Description

Each treatment will utilize 600 mg (1.2 mL) of Magnesium Sulfate Sandoz

Intervention Type

Drug

Intervention Name(s)

Sodium Chloride , USP PPC

Other Intervention Name(s)

Sodium Chloride for Injection USP Omega Laboratories Ltd.

Intervention Description

Intervention: The control group will receive Sodium Chloride , USP PPC (1.2 mL hypertonic 5.5% saline with 5 mg Salbutamol - GlaxoSmithKline/Pharmascience

Primary Outcome Measure Information:

Title

Hospitalization of Subject

Description

Defined as admission to an inpatient unit within 24hours of the start of experimental therapy due to continued/worsening distress.

Time Frame

Up to 24 hours after treatment

Secondary Outcome Measure Information:

Title

Pediatric Respiratory Assessment Measure (PRAM)

Description

PRAM is a validated measure of asthma severity in the Emergency Department

Time Frame

0, 20, 40 60, 120, 180, 240 minutes post dose

Title

Changes in Vitals

Description

Respiratory Rate, O2 saturation, Blood pressure

Time Frame

0, 20, 40, 60, 120, 180, 240 minutes post dose

Title

Number of Salbutamol Treatments

Description

This measure of additional therapy may strengthen the measure of benefit of inhaled magnesium

Time Frame

Up to 240 minutes post dose

Title

Medical History and Phenotype

Description

Time Frame

Baseline

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 2-17 years of age Diagnosis of asthma/reactive airways/viral wheeze, 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). Persistent moderate to severe airway obstruction after 3 doses of salbutamol and ipratropium (as per site specific standard of care guidelines) -, 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 severity and has a high likelihood of being hospitalized.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: 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. Patients who have already received IV Mg therapy during the index visit. Critically ill children requiring immediate intubation. These children need immediate ICU management and hospitalization. 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. Known co-existent renal, chronic pulmonary, neurologic, cardiac or systemic disease. These conditions may influence the response to Mg and hospitalization. Known hypersensitivity to Mg sulfate. Patients previously enrolled in the study. Insufficient command of the English and or French language. Lack of a home or cellular telephone. Known allergy/sensitivity to latex.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Suzanne Schuh, MD

Organizational Affiliation

The Hospital for Sick Children

Official's Role

Principal Investigator

Facility Information:

Facility Name

Alberta Children's Hospital

City

Calgary

State/Province

Alberta

ZIP/Postal Code

T3B 6A8

Country

Canada

Facility Name

Stollery Hospital

City

Edmonton

State/Province

Alberta

ZIP/Postal Code

T6G1C9

Country

Canada

Facility Name

BC Children's Hospital

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V6H 3V4

Country

Canada

Facility Name

The Manitoba Institute of Child Health

City

Winnipeg

State/Province

Manitoba

ZIP/Postal Code

R3E3P4

Country

Canada

Facility Name

Children's Hospital of Eastern Ontario

City

Ottawa

State/Province

Ontario

ZIP/Postal Code

K1H8L1

Country

Canada

Facility Name

The Hospital for Sick Children

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5V1X8

Country

Canada

Facility Name

Ste Justine Hospital

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H3T1C5

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34279646

Citation

Schuh S, Freedman SB, Zemek R, Plint AC, Johnson DW, Ducharme F, Gravel J, Thompson G, Curtis S, Stephens D, Coates AL, Black KJ, Beer D, Sweeney J, Rumantir M, Finkelstein Y; Pediatric Emergency Research Canada. Association Between Intravenous Magnesium Therapy in the Emergency Department and Subsequent Hospitalization Among Pediatric Patients With Refractory Acute Asthma: Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2021 Jul 1;4(7):e2117542. doi: 10.1001/jamanetworkopen.2021.17542.

Results Reference

derived

PubMed Identifier

33231663

Citation

Schuh S, Sweeney J, Rumantir M, Coates AL, Willan AR, Stephens D, Atenafu EG, Finkelstein Y, Thompson G, Zemek R, Plint AC, Gravel J, Ducharme FM, Johnson DW, Black K, Curtis S, Beer D, Klassen TP, Nicksy D, Freedman SB; Pediatric Emergency Research Canada (PERC) Network. Effect of Nebulized Magnesium vs Placebo Added to Albuterol on Hospitalization Among Children With Refractory Acute Asthma Treated in the Emergency Department: A Randomized Clinical Trial. JAMA. 2020 Nov 24;324(20):2038-2047. doi: 10.1001/jama.2020.19839.

Results Reference

derived

PubMed Identifier

27220675

Citation

Schuh S, Sweeney J, Freedman SB, Coates AL, Johnson DW, Thompson G, Gravel J, Ducharme FM, Zemek R, Plint AC, Beer D, Klassen T, Curtis S, Black K, Nicksy D, Willan AR; Pediatric Emergency Research Canada Group. Magnesium nebulization utilization in management of pediatric asthma (MagNUM PA) trial: study protocol for a randomized controlled trial. Trials. 2016 May 24;17(1):261. doi: 10.1186/s13063-015-1151-x.

Results Reference

derived

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Magnesium Nebulization Utilization in Management of Pediatric Asthma

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