Intranasal fentanyl versus intravenous morphine in the emergency department treatment of severe painful sickle cell crises in children: study protocol for a randomised controlled trial.
BACKGROUND
Children with sickle cell disease (SCD) frequently and unpredictably present to the emergency department (ED) with pain. The painful event is the hallmark acute clinical manifestation of SCD, characterised by sudden onset and is usually bony in origin. This study aims to establish if 1.5mcg/kg of intranasal fentanyl (INF; administered via a Mucosal Atomiser Device, MAD™) is non-inferior to intravenous morphine 0.1 mg/kg in severe SCD-associated pain.


METHODS
This study is a randomised,double-blind, double-dummy active control trial of children (weighing more than 10 kg) between 1 year and 21 years of age with severe painful sickle cell crisis. Severe pain is defined as rated seven or greater on a 0 to 10 age-appropriate numeric pain scale or equivalent. The trial will be conducted in a single tertiary urban paediatric ED in Dublin, Ireland. Each patient will receive a single active agent and a single placebo via the intravenous and intranasal routes. All clinical and research staff, patients and parents will be blinded to the treatment allocation. The primary endpoint is severity of pain scored at 10 min from administration of the study medications. Secondary endpoints include pain severity measured at 0, 5, 15, 20, 30, 60 and 120 min after the administration of analgesia, proportion of patients requiring rescue analgesia and incidence of adverse events. The trial ends at 120 min after the administration of the study drugs. A clinically meaningful difference in validated pain scores has been defined as 13 mm. Setting the permitted threshold to 50% of this limit (6 mm) and assuming both treatments are on average equal, a sample size of 30 patients (15 per group) will provide at least 80% power to demonstrate that INF is non-inferior to IV morphine with a level of significance of 0.05.


CONCLUSIONS
This clinical trial will inform of the role of INF 1.5mcg/kg via MAD in the acute treatment of severe painful sickle cell crisis in children in the ED setting.


BACKGROUND
Current Controlled Trials ISRCTN67469672 and EudraCT no. 2011-005161-20.
Paediatric Emergency Research Unit (PERU), Emergency Department, Our Lady's Children's Hospital (OLCHC), Crumlin, Dublin 12, Ireland.
Michael Joseph
MJ
Barrett
John
J
Cronin
Adrian
A
Murphy
Siobhan
S
McCoy
John
J
Hayden
SinéadNic
S
an Fhailí
Tim
T
Grant
Abel
A
Wakai
Corrina
C
McMahon
Sean
S
Walsh
Ronan
R
O'Sullivan
D000281:Administration, Intranasal; D000293:Adolescent; D000336:Aerosols; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D000755:Anemia, Sickle Cell / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004636:Emergency Service, Hospital; D005283:Fentanyl / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D007494:Ireland; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects; D009330:Nebulizers and Vaporizers; D010146:Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D012107:Research Design; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000336:Aerosols; D000701:Analgesics, Opioid; D009020:Morphine; D005283:Fentanyl