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.

Abstract

Multiple recent Sickle Cell Disease studies have been terminated due to poor enrollment. We developed methods to overcome past barriers and utilized these to study the efficacy and safety of intravenous magnesium for vaso-occlusive crisis (VOC). We describe the methods of the Intravenous Magnesium in Sickle Vaso-occlusive Crisis (MAGiC) trial and discuss methods used to overcome past barriers. MAGiC was a multi-center randomized double-blind placebo-controlled trial of intravenous magnesium versus normal saline for treatment of VOC. The study was a collaboration between Pediatric Hematologists and Emergency Physicians in the Pediatric Emergency Care Applied Research Network (PECARN). Eligible patients were randomized within 12 hours of receiving intravenous opioids in the Emergency Department (ED) and administered study medication every 8 hours. The primary outcome was hospital length of stay. Associated plasma studies elucidated magnesium's mechanism of action and the pathophysiology of VOC. Health-related quality of life was measured. Site-, protocol-, and patient-related barriers from prior studies were identified and addressed. Limited study staff availability, lack of collaboration with the ED, and difficulty obtaining consent were previously identified barriers. Leveraging PECARN resources, forging close collaborations between Sickle Cell Centers and EDs of participating sites, and approaching eligible patients for prior consent helped overcome these barriers. Participation in the PECARN network and establishment of collaborative arrangements between Sickle Cell Centers and their affiliated EDs are major innovative features of the MAGiC study that allowed improved subject capture. These methods could serve as a model for future studies of VOCs.

Trial registration: ClinicalTrials.gov NCT01197417.

Keywords: enrollment; hematology; hemoglobinopathies; pain medicine; randomized controlled trial; sickle cell anemia; sickle cell disease; vaso-occlusive crisis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anemia, Sickle Cell / blood
  • Anemia, Sickle Cell / complications*
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / pharmacology
  • Arterial Occlusive Diseases / blood
  • Arterial Occlusive Diseases / drug therapy*
  • Arterial Occlusive Diseases / etiology
  • Biomarkers / blood
  • Cooperative Behavior
  • Cytokines / blood
  • Emergency Service, Hospital / organization & administration
  • Hospitals, Pediatric / organization & administration
  • Hospitals, Special / organization & administration
  • Humans
  • Hypotension / chemically induced
  • Informed Consent
  • Infusions, Intravenous
  • Interdisciplinary Communication*
  • Interprofessional Relations
  • Length of Stay / statistics & numerical data
  • Magnesium Sulfate / adverse effects
  • Magnesium Sulfate / pharmacology
  • Magnesium Sulfate / therapeutic use*
  • Narcotics / therapeutic use
  • Pain / drug therapy
  • Pain / etiology
  • Quality of Life
  • Randomized Controlled Trials as Topic / methods*
  • Vasodilator Agents / adverse effects
  • Vasodilator Agents / pharmacology
  • Vasodilator Agents / therapeutic use*

Substances

  • Anti-Inflammatory Agents
  • Biomarkers
  • Cytokines
  • Narcotics
  • Vasodilator Agents
  • Magnesium Sulfate

Associated data

  • ClinicalTrials.gov/NCT01197417