Intravenous Magnesium for Sickle Cell Vasoocclusive Crisis

Sickle Cell Disease Clinical Trial

— MAGiC  

Official title:

Intravenous Magnesium for Sickle Cell Vasoocclusive Crisis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01197417
• Other study ID #: PECARN 025
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: August 31, 2010
• Last updated: December 21, 2015
• Start date: December 2010
• Est. completion date: March 2014

Study information

• Verified date: December 2015
• Source: Medical College of Wisconsin
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 208
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 4 Years to 21 Years

Eligibility

Inclusion Criteria:

• age 4-21 years, inclusive

• Sickle cell anemia (Hb SS) or Sickle beta zero thalassemia disease (Hb Sß°)

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

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

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Baylor College of Medicine	Houston	Texas
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Children's Hospital of Philadelphia Research Institute	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Medical College of Wisconsin	Pediatric Emergency Care Applied Research Network

Country where clinical trial is conducted

United States, 

References & Publications (1)

Brousseau DC, Scott JP, Badaki-Makun O, Darbari DS, Chumpitazi CE, Airewele GE, Ellison AM, Smith-Whitley K, Mahajan P, Sarnaik SA, Casper TC, Cook LJ, Dean JM, Leonard J, Hulbert ML, Powell EC, Liem RI, Hickey R, Krishnamurti L, Hillery CA, Nimmer M, Pan — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	Rehospitalization		Rehospitalization will be measured at 7 days post discharge and at the follow-up visit (on average, 30 days post discharge)	Yes
Secondary	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	Yes
Secondary	Hospital Length of Stay		Start of first study drug infusion to actual hospital discharge	No