Intranasal Fentanyl Versus Intravenous Morphine in the Treatment of Severe Painful Sickle Cell Crises in Children
Intranasal Fentanyl Versus Intravenous Morphine in the Treatment of Severe Painful Sickle Cell Crises in Children
Sickle cell anaemia is an inherited blood disorder which results in abnormal sickle shaped
 red blood cells which do not fit well through small blood vessels. These blockages prevent
 oxygen (in blood) from reaching different parts of the body resulting in painful crisis. This
 study will compare the effectiveness of two types of pain medication, one given through a
 vein and one squirted up the nose.
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.

 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.

 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.
Inclusion Criteria:

 -  Ages 1 - 21 years

 -  Weight ≥10 kg and ≤70 kg

 -  Known sickle cell disease presenting with severe pain

 -  Written informed consent, ideally from both parents (and assent, where appropriate),
 obtained prior to painful crisis (for example, in Haematology clinic)

 -  Verbal consent (and assent, where appropriate) obtained at the time of the painful
 crisis in the ED

 -  Hospital admission required for painful crisis

 Exclusion Criteria:

 -  Patient has received parenteral narcotic analgesic within 4 hours of ED presentation

 -  Oxygen saturations below 95% on initial assessment

 -  Altered conscious state as defined by a Glasgow Coma score less than 15

 -  Contraindications to fentanyl/morphine usage

 -  Inability to secure IV access

 -  Patient has participated in another clinical trial involving an Investigation
 Medicinal Product (IMP) within 4 weeks of dosing, or is currently enrolled in another
 clinical trial involving an IMP, or has been previously enrolled in this trial

 -  Patients who have any condition that would make him/her, in the opinion of the
 Investigator or Sponsor, unsuitable for the study, or who are, in the opinion of the
 Investigator, not likely to complete the study for any reason

 -  Blocked or traumatised nose