Intravenous Magnesium for Sickle Cell Vasoocclusive Crisis

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and efficacy of intravenous magnesium in shortening the duration of a pain crisis and to determine the health-related quality of life and short term outcomes of children treated with intravenous magnesium during an acute pain crisis.

Detailed Description
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It is well known that children with sickle cell disease are at risk for acute pain crises. The usual treatment for these pain crises, intravenous fluids and pain medicines such as morphine, has changed little over the past three decades. In a pilot study, the addition of intravenous magnesium to standard therapy decreased length of stay; however, this study was not randomized, not blinded, not placebo-controlled, and not adequately powered to assess safety. We will conduct a multi-center, randomized, double-blind, placebo controlled trial of about 208 children, ages 4-21 years. Patients will be randomized to receive intravenous magnesium sulfate or placebo every 8 hours for a total of 6 doses, or until discharge. Patients will return for a routine clinic visit up to 3 months after discharge for a baseline assessment. Patients will also complete health-related quality of life measures at 4 timepoints throughout the study.

Official Title
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Intravenous Magnesium for Sickle Cell Vasoocclusive Crisis

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: Intravenous Magnesium Sulfate
* Drug: Normal Saline Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 4-21 years, inclusive Sickle cell anemia (Hb SS) or Sickle beta zero thalassemia disease (Hb Sβ°) failed intravenous opioid pain management in the emergency department prior to the decision to admit the patient admitted to the inpatient unit for sickle cell pain crisis Exclusion Criteria: patient received more than 12 hours of intravenous pain medication prior to enrollment previous enrollment in this study (only one admission per child is eligible) history of allergy/intolerance to both intravenous morphine and hydromorphone known other cause for pain (avascular necrosis, gall bladder disease, priapism, etc.) patient with greater than 10 admissions for pain crisis in the past year patient maintained on daily opioids or chronic transfusions for chronic sickle cell pain transfusion within the previous two months known kidney or liver failure (elevation of liver function tests does not warrant exclusion) known pulmonary hypertension pregnancy diagnosis of bacterial infection, fever ≥39.5°C, acute chest syndrome, hemodynamic instability or sepsis current oral magnesium supplementation or current enrollment in another therapeutic study protocol previously diagnosed clinical stroke current or planned use of neuromuscular blocker, nifedipine, ritodrine, or terbutaline allergy to magnesium sulfate discharge from an inpatient unit within 72 hours of arrival in the emergency department for the current pain crisis

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 21 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Magnesium group<br>Intravenous Magnesium Sulfate | Drug: Intravenous Magnesium Sulfate<br>* 40 mg/kg (max 2.4 grams), infused at a concentration of 40 mg/ml (1 ml/kg, max 60 ml), every 8 hours for a total of 6 doses<br>|
| Placebo Comparator: Placebo group<br>Normal Saline placebo | Drug: Normal Saline Placebo<br>* (1 ml/kg, max 60 ml), administered every 8 hours for a total of 6 doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital Length of Stay (Hours) |  | From the time of the start of first study med infusion until hospital discharge or 12 hours after the last IV opioid, whichever occurs first, up to 10 days post enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Morphine Equivalents Per Kilogram of Body Weight Used During Hospitalization |  | Total morphine equivalents used during the hospitalization will be recorded on the day of discharge, up to 10 days post enrollment | 
| Hypotension Associated With Infusion | For each study drug infusion, systolic blood pressure (SBP) was measured just prior to the start of the infusion and again every 10 minutes until 30 minutes until the end of the infusion. Hypotension was defined as a greater than 20% reduction in SBP relative to corresponding baseline measurement for any study drug infusion. | Blood pressure will be monitored every 8 hours, concurrent with each infusion, and for 20-30 minutes after infusion completion, until discharge, up to 2 days post enrollment | 
| Warm Sensation Associated With Study Drug Infusion | Patient spontaneously reported feelings of warmth during any study drug infusion. | Patient-reported warm sensation upon infusion will be monitored every 8 hours, concurrent with each infusion, and for 20-30 minutes after infusion completion, until discharge, up to 2 days post enrollment | 
| Rehospitalization |  | Rehospitalization will be measured at 7 days post discharge and at the follow-up visit (on average, 30 days post discharge) | 
| Development of Acute Chest Syndrome (ACS) |  | Patients will be monitored daily, on average, during their length of stay until discharge, up to 10 days post enrollment | 
| Hospital Length of Stay |  | Start of first study drug infusion to actual hospital discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle Cell Disease, Magnesium Sulfate, Pediatric