Clinical trial NCT01197417: Intravenous Magnesium for Sickle Cell Vasoocclusive Crisis
Official title: Intravenous Magnesium for Sickle Cell Vasoocclusive Crisis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Sickle Cell Disease
Keywords: Sickle Cell Disease
Magnesium Sulfate
Pediatric
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
Collaborators: name: Pediatric Emergency Care Applied Research Network
First posted: 2010-09-09
Enrollment: 208
Sex: ALL
Minimum age (years): 4
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Hospital Length of Stay (Hours)
timeFrame: 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 outcomes:
measure: Number of Morphine Equivalents Per Kilogram of Body Weight Used During Hospitalization
timeFrame: Total morphine equivalents used during the hospitalization will be recorded on the day of discharge, up to 10 days post enrollment
measure: Hypotension Associated With Infusion
timeFrame: 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
measure: Warm Sensation Associated With Study Drug Infusion
timeFrame: 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
measure: Rehospitalization
timeFrame: Rehospitalization will be measured at 7 days post discharge and at the follow-up visit (on average, 30 days post discharge)
measure: Development of Acute Chest Syndrome (ACS)
timeFrame: Patients will be monitored daily, on average, during their length of stay until discharge, up to 10 days post enrollment
measure: Hospital Length of Stay
timeFrame: Start of first study drug infusion to actual hospital discharge
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia Research Institute
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Medical College of Wisconsin
name: David Brousseau, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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, Panepinto JA; Pediatric Emergency Care Applied Research Network (PECARN). A multicenter randomized controlled trial of intravenous magnesium for sickle cell pain crisis in children. Blood. 2015 Oct 1;126(14):1651-7. doi: 10.1182/blood-2015-05-647107. Epub 2015 Jul 31.
citation: Panepinto JA, Paul Scott J, Badaki-Makun O, Darbari DS, Chumpitazi CE, Airewele GE, Ellison AM, Smith-Whitley K, Mahajan P, Sarnaik SA, Charles Casper T, Cook LJ, Leonard J, Hulbert ML, Powell EC, Liem RI, Hickey R, Krishnamurti L, Hillery CA, Brousseau DC; Pediatric Emergency Care Applied Research Network (PECARN). Determining the longitudinal validity and meaningful differences in HRQL of the PedsQL Sickle Cell Disease Module. Health Qual Life Outcomes. 2017 Jun 12;15(1):124. doi: 10.1186/s12955-017-0700-2.
citation: Badaki-Makun O, Scott JP, Panepinto JA, Casper TC, Hillery CA, Dean JM, Brousseau DC; Pediatric Emergency Care Applied Research Network (PECARN) Magnesium in Sickle Cell Crisis (MAGiC) Study Group. Intravenous magnesium for pediatric sickle cell vaso-occlusive crisis: methodological issues of a randomized controlled trial. Pediatr Blood Cancer. 2014 Jun;61(6):1049-54. doi: 10.1002/pbc.24925. Epub 2014 Jan 17.