Intravenous Magnesium for Sickle Cell Vasoocclusive Crisis

Phase 2

Completed

Interventions: Drug: Intravenous Magnesium Sulfate
Drug: Normal Saline Placebo

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Magnesium group	Intravenous Magnesium Sulfate	Intravenous Magnesium Sulfate
Placebo group	Normal Saline Placebo	Normal Saline placebo

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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	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	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.
Warm Sensation Associated With 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	Patient spontaneously reported feelings of warmth during any study drug infusion.
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

Locations (8): Children's Hospital of Philadelphia Research Institute
🇺🇸
Philadelphia, Pennsylvania, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
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Chicago, Illinois, United States
Johns Hopkins Hospital
🇺🇸
Baltimore, Maryland, United States
Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
University of Pittsburgh
🇺🇸
Pittsburgh, Pennsylvania, United States
Children's Hospital of Michigan
🇺🇸
Detroit, Michigan, United States
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States