Official Title

Intravenous Magnesium for Sickle Cell Vasoocclusive Crisis
  • Phase

    Phase 2/Phase 3
  • Study Type

    Interventional
  • Study Participants

    208
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.
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.
Study Started
Dec 31
2010
Primary Completion
Mar 31
2014
Study Completion
Mar 31
2014
Results Posted
Sep 07
2015
Estimate
Last Update
Jan 27
2016
Estimate

Drug Intravenous Magnesium Sulfate

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

Drug Normal Saline Placebo

(1 ml/kg, max 60 ml), administered every 8 hours for a total of 6 doses

Magnesium group Experimental

Intravenous Magnesium Sulfate

Placebo group Placebo Comparator

Normal Saline placebo

Criteria

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

Summary

Magnesium Group

Placebo Group

All Events

Event Type Organ System Event Term Magnesium Group Placebo Group

Hospital Length of Stay (Hours)

Magnesium Group

56.0
hours (Median)
Inter-Quartile Range: 27.0 to 109.0

Placebo Group

47.0
hours (Median)
Inter-Quartile Range: 24.0 to 99.0

Number of Morphine Equivalents Per Kilogram of Body Weight Used During Hospitalization

Magnesium Group

1.46
mg Morphine/kg (Median)
Inter-Quartile Range: 0.55 to 3.32

Placebo Group

1.28
mg Morphine/kg (Median)
Inter-Quartile Range: 0.4 to 3.29

Hospital Length of Stay

Magnesium Group

74.5
Hours (Median)
Inter-Quartile Range: 39.5 to 123.5

Placebo Group

60.5
Hours (Median)
Inter-Quartile Range: 37.0 to 122.0

Warm Sensation Associated With Study Drug Infusion

Patient spontaneously reported feelings of warmth during any study drug infusion.

Magnesium Group

26.0
Participant

Placebo Group

2.0
Participant

Rehospitalization

Magnesium Group

12.0
Participant

Placebo Group

7.0
Participant

Development of Acute Chest Syndrome (ACS)

Magnesium Group

16.0
Paricipants

Placebo Group

14.0
Paricipants

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.

Magnesium Group

4.0
Participant

Placebo Group

1.0
Participant

Total

208
Participants

Age, Continuous

13.6
years (Mean)
Standard Deviation: 4.7

Age, Categorical

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

Region of Enrollment

Sex: Female, Male

Overall Study

Magnesium Group

Placebo Group

Drop/Withdrawal Reasons

Magnesium Group

Placebo Group