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 (Trials)

Background: Children with sickle cell disease (SCD) frequently and unpredictably present to theemergency department (ED) with pain. The painful event is the hallmark acute clinicalmanifestation of SCD, characterised by sudden onset and is usually bony in origin. This studyaims to establish if 1.5mcg/kg of intranasal fentanyl (INF; administered via a MucosalAtomiser Device, MADTM) is non-inferior to intravenous morphine 0.1 mg/kg in severeSCD-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 sicklecell crisis. Severe pain is defined as rated seven or greater on a 0 to 10 age-appropriatenumeric pain scale or equivalent. The trial will be conducted in a single tertiary urbanpaediatric ED in Dublin, Ireland. Each patient will receive a single active agent and a singleplacebo via the intravenous and intranasal routes. All clinical and research staff, patients andparents will be blinded to the treatment allocation. The primary endpoint is severity of painscored at 10 min from administration of the study medications. Secondary endpoints includepain severity measured at 0, 5, 15, 20, 30, 60 and 120 min after the administration ofanalgesia, 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 meaningfuldifference in validated pain scores has been defined as 13 mm. Setting the permittedthreshold to 50% of this limit (6 mm) and assuming both treatments are on average equal, asample size of 30 patients (15 per group) will provide at least 80% power to demonstrate thatINF is non-inferior to IV morphine with a level of significance of 0.05.DiscussionThis clinical trial will inform of the role of INF 1.5mcg/kg via MAD in the acute treatment ofsevere painful sickle cell crisis in children in the ED setting.Trial registrationCurrent Controlled Trials ISRCTN67469672 and EudraCT no. 2011-005161-20