Timely Intravenous Magnesium for Asthma in Children

NCT ID: NCT05166811

Last Updated: 2024-12-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-12
• Study Completion Date: 2023-07-31

Brief Summary

Many children currently being hospitalized with severe asthma could potentially avoid hospitalization and be sent home if their treatment in the emergency department was more effective. The investigators will conduct a pilot trial that will lead to a larger study to conclusively answer whether a simple and inexpensive medicine, intravenous magnesium sulfate, can be used in the emergency department to prevent hospitalization for these children.

Detailed Description

5.4.1 Acquisition The specific study agent to be used in this pilot trial is Magnesium Sulfate in Water for Injection, a sterile, nonpyrogenic solution of magnesium sulfate heptahydrate in water. Study agent will be acquired by each hospital's research pharmacy from Pfizer, Inc as a solution of magnesium sulfate in water at 80 mg/mL. Agent will be shipped directly from Pfizer to each study hospital pharmacy.

5.4.2 Preparation, Storage & Labeling Doses for each IVMg arm will be prepared in identical manner, by drawing a specified volume of Intravenous Magnesium Sulfate (IVMg) from the commercial container using sterile technique and mixing in a polyvinylchloride container with a specified volume of sterile water. For the 50 mg/kg arm, this will be accomplished by mixing 25 mL of IVMg (80 mg/mL) with 15 mL of sterile water for a final concentration of 50 mg/mL and volume of 40 mL. For the 75 mg/kg arm, this will be accomplished by mixing 37.5 mL of IVMg (80 mg/mL) with 2.5 mL of sterile water for a final concentration of 75 mg/mL and volume of 40 mL. For the placebo arm, 40 mL of 0.9% sodium chloride solution will be drawn into a polyvinylchloride container identical in appearance to the containers used for the IVMg arms. Each prepared dose will be labeled according to the sequential randomization scheme and stored according to local pharmacy procedure. Unused doses prepared locally will be replaced after one week of storage.

5.4.3 Dosing Schedule

After randomization the institutional pharmacist will draw equivolumetric dosages (1 mL/kg, with max of 40 mL) from previously prepared vials. Enrolled subjects will be randomized to one of three arms:

• IVMg 75 mg/kg arm: 75 mg/kg (max 3 gm) infused over 20 minutes through a peripheral IV catheter
• IVMg 50 mg/kg arm: 50 mg/kg (max 2 gm) infused over 20 minutes through a peripheral IV catheter
• Placebo arm: 1 mL/kg (max 40 ml) of normal saline over 20 minutes through a peripheral IV catheter 5.4.4 Dose Modification for Potential Toxicity Clinicians will not administer IVMg to enrolled subjects outside of the study protocol until study outcomes have been determined 2 hours after the start of the infusion. The half-life of IVMg is approximately 2 hours.49 Repeated-dose protocols in an ICU setting that gave as much as 125 mg/kg IVMg to children with asthma over two hours produced no hypotension or other serious adverse effects.47 Because of this margin of safety, open-label IVMg 50 mg/kg can be administered safely 2 hours after the study infusion under strict study monitoring protocols without need for unblinding.

Conditions

Asthma

Keywords

asthma; IV Magnesium

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

75 mg/kg

Doses for each IVMg arm will be prepared in identical manner, by drawing a specified volume of IVMg from the commercial container using sterile technique and mixing in a polyvinylchloride container with a specified volume of sterile water. For the 75 mg/kg arm, this will be accomplished by mixing 37.5 mL of IVMg (80 mg/mL) with 2.5 mL of sterile water for a final concentration of 75 mg/mL and volume of 40 mL. After randomization the institutional pharmacist will draw dosages (1 mL/kg, with max of 40 mL) from previously prepared vials. The dose will be delivered by the clinical nurse over 20 minutes through a peripheral IV.

Group Type: ACTIVE_COMPARATOR

Magnesium Sulfate, Heptahydrate

Intervention Type: DRUG

A single dose of intravenous magnesium sulfate given over 20 minutes through a peripheral intravenous line. Two arms of the study will deliver intravenous magnesium, one at a dose of 50 mg/kg, and the other at a dose of 75 mg/kg.

50 mg/kg

Doses for each IVMg arm will be prepared in identical manner, by drawing a specified volume of IVMg from the commercial container using sterile technique and mixing in a polyvinylchloride container with a specified volume of sterile water. For the 50 mg/kg arm, this will be accomplished by mixing 25 mL of IVMg (80 mg/mL) with 15 mL of sterile water for a final concentration of 50 mg/mL and volume of 40 mL. After randomization the institutional pharmacist will draw dosages (1 mL/kg, with max of 40 mL) from previously prepared vials. The dose will be delivered by the clinical nurse over 20 minutes through a peripheral IV.

Group Type: ACTIVE_COMPARATOR

Magnesium Sulfate, Heptahydrate

Intervention Type: DRUG

A single dose of intravenous magnesium sulfate given over 20 minutes through a peripheral intravenous line. Two arms of the study will deliver intravenous magnesium, one at a dose of 50 mg/kg, and the other at a dose of 75 mg/kg.

Placebo

For the placebo arm, 40 mL of 0.9% sodium chloride solution will be drawn into a polyvinylchloride container identical in appearance to the containers used for the IVMg arms. After randomization the institutional pharmacist will draw dosages (1 mL/kg, with max of 40 mL) from previously prepared vials. The dose will be delivered by the clinical nurse over 20 minutes through a peripheral IV.

Group Type: PLACEBO_COMPARATOR

0.9% saline

Intervention Type: DRUG

A single dose of intravenous 0.9% sodium chloride given over 20 minutes through a peripheral intravenous line as the placebo arm of the study.

Interventions

Magnesium Sulfate, Heptahydrate

A single dose of intravenous magnesium sulfate given over 20 minutes through a peripheral intravenous line. Two arms of the study will deliver intravenous magnesium, one at a dose of 50 mg/kg, and the other at a dose of 75 mg/kg.

Intervention Type: DRUG

0.9% saline

A single dose of intravenous 0.9% sodium chloride given over 20 minutes through a peripheral intravenous line as the placebo arm of the study.

Intervention Type: DRUG

Other Intervention Names

Intravenous magnesium sulfate; normal saline; 0.9% sodium chloride

Eligibility Criteria

Inclusion Criteria

1. A prior physician diagnosis of asthma confirmed by a treating physician in the ED who has spoken with the patient and family and reviewed the medical record (ED attending or fellow physician)

2. Severe acute asthma, defined as a Pediatric Respiratory Assessment Measure (PRAM) score of 7 or greater as assessed by a treating physician at the time of screening using the study scoring instrument, which takes 60 seconds to complete

3. Children 2-17 years of age

Exclusion Criteria

• Known pregnancy (by patient or parent report) or positive pregnancy test on females 12 years of age and older
• Age-adjusted hypotension at presentation using age-based Pediatric Advanced Life Support parameters (children >1 year to 10 years, systolic blood pressure (SBP)<(70 + 2 x age in years); >10 years, SBP < 90 mmHg)71
• Known severe renal impairment (by parent or patient report)
• Application of assisted ventilation before enrollment assessment (intubated, bi-level positive airway pressure, continuous positive airway pressure)
• Received IVMg within 24 hours prior to screening (by parent or patient report or medical record review)
• Enrollment assessment is 60 minutes after the start of ED treatment (start of first albuterol treatment)
• Previous enrollment in the same trial (by research coordinator review of trial records)

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital of Philadelphia

OTHER

Sponsor Role: collaborator

Nationwide Children's Hospital

OTHER

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Utah

OTHER

Sponsor Role: lead

Responsible Party

Mike Johnson

Associate Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Nationwide Children's Hospital

Columbus, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Primary Children's Hospital

Salt Lake City, Utah, United States

Countries

United States

References

Johnson MD, Barney BJ, Rower JE, Finkelstein Y, Zorc JJ. Intravenous Magnesium: Prompt Use for Asthma in Children Treated in the Emergency Department (IMPACT-ED): Protocol for a Multicenter Pilot Randomized Controlled Trial. JMIR Res Protoc. 2023 Jul 17;12:e48302. doi: 10.2196/48302.

Reference Type: DERIVED

PMID: 37459153 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form: Parental Permission

View Document

Document Type: Informed Consent Form: Assent

View Document

Other Identifiers

1R34HL152047-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB 104082

Identifier Type: -

Identifier Source: org_study_id