Intranasal Sufentanil for Analgesia of Severe Sickle Cell Vaso-occlusive Pain Crisis in the Pediatric Emergency Department

INTERVENTION: Product Name: Sufentanil Mylan 50 microgrammes/ml solution injectable,Product Code: PRD2658528,Pharmaceutical Form: SOLUTION FOR INJECTION,Other descriptive name: ,Strength: Sufentanil 50µg,Product Name: CHLORURE DE SODIUM 0,9 % LAVOISIER, solution pour perfusion,Product Code: PRD470771,Pharmaceutical Form: SOLUTION FOR INFUSION,Other descriptive name: ,Strength: Sodium Chloride 0.045g / 5mL,Pharmaceutical form of the placebo: SOLUTION FOR INFUSION,Route of administration of the placebo: NASAL USE,Product Name: MORPHINE HYDROCHLORIDE,Product Code: SUB14596MIG,Pharmaceutical Form: SOLUTION FOR INJECTION,Other descriptive name: ,Strength: 50mg / 5mL CONDITION: MedDRA version: 20.0Level: LLTClassification code: 10072397Term: Vaso‐occlusive crisisSystem Organ Class: 10005329 Therapeutic area: Diseases [C] ‐ Hemic and Lymphatic Diseases [C15]‐Diseases [C] ‐ Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] vaso‐occlusive crisis due to sickle cell disease ; MedDRA version: 20.0Level: LLTClassification code: 10072397Term: Vaso‐occlusive crisisSystem Organ Class: 10005329 SECONDARY OUTCOME: Secondary end point(s):a) Proportion of children relieved (EVENDOL = 5/15 or NRS‐11 = 3/10) at 10, 20, 40, 50 and 60 minutes after the IN spray; Secondary end point(s):b) Proportion of children with a moderate pain (EVENDOL = 9/15 or NRS‐11 = 6/10) at 10, 20, 30, 40, 50 and 60 minutes after the IN spray; Secondary end point(s):c) Time from triage to relief (EVENDOL = 5/15 or NRS‐11 = 3/10) Time from triage to venous access Time from triage to IV morphine initiation Proportion of children with a first dose of opioids within 30 min of arrival Time from triage to parenteral opioid initiation (IV morphine or IN Sufentanil) Time from triage to admission/discharge decision Secondary end point(s):d) Morphine consumption (mg) 60, 120 and 240 minutes after the IN injection; Secondary end point(s):e) Rates of hypotension, hypoxia, bradycardia, respiratory distress, headache, nausea, vomiting, sleepiness and itchiness until 4 hours after the IN injection; Secondary end point(s):f) All adverse events; Secondary end point(s):g) Rate of admission after the ED visit Length of hospital stay: at hospital discharge; Secondary end point(s):h) Rate of Acute chest syndrome: at hospital discharge Rate of admission in ICU, invasive ventilation, non‐invasive ventilation, oxygene therapy: at hospital discharge Rate of Transfusion: at hospital discharge Rate of death: at hospital discharge Secondary end point(s):i) Satisfaction with the quality of analgesia and management during the emergency room stay = o For children > 8 years ‐ Total Quality Pain Management and Desire to receive the same intranasal treatment during a future severe VOC by children and parent o For children = 8 years ‐ Global satisfaction with treatment (NRS‐11, by parent and patient) ‐ Total Quality Pain Management and Desire to receive the same intranasal treatment during a future severe VOC only by parent PRIMARY OUTCOME: Main Objective:To demonstrate the superiority of a procedure consisting in IN administration of sufentanil followed by IV administration of morphine as soon as possible {IN sufentanil + IV morphine (as a standard of care) }, when compared to placebo and IV administration of morphine as soon as possible {IN Placebo + IV morphine (as a standard of care)}, on the efficacy of the analgesia at 30 minutes, in children with SCD presenting to the pediatric ED with a severe VOC. Primary end point(s):Proportion of children relieved at 30 minutes after the IN spray. The pain will be evaluated with : An hetero‐evaluation by the EVENDOL Scale for children aged less than 8 years. An auto‐evaluation by the Numeric Pain Rating Scale (NRS‐11) for children aged 8 years to less than 18 years. Pain relief is defined as EVENDOL score = 5/15 or NRS‐11 score = 3/10. Secondary Objective:a)To demonstrate the superiority of the {IN Sufentanil +IV morphine (as a standard of care)} procedure, when compared to {IN Placebo + IV morphine (as a standard of care)} procedure, on the efficacy of the analgesia at 10, 20, 40, 50 and 60 minutes after the IN spray,b)To demonstrate the superiority of the {IN Sufentanil +IV morphine (as a standard of care)} procedure, when compared to {IN Placebo + IV morphine (as a standard of care)} procedure, on the efficacy of the analgesia “moderate” at 10, 20, 30, 40, 50 and 60 minutes after the IN spray,c)To demonstrate that {IN Sufentanil +IV morphine(as a standard of care)} procedure, when compared to {IN Placebo + IV morphine(as a standard of care)} procedure, is able to decrease the delay before relief, the delay before administration of others opioid analgesics, and the duration of the ED visit,d)To demonstrate that {IN Sufentanil +IV morphine(as a standard of care)} procedure, when compared to {IN Placebo + IV morphine (as a standard of care)} procedure, is able to decrease the level of morphine consumption,e)To demonstrate the safety of the {IN Sufentanil +IV morphine(as a standard of care)} procedure, when compared to {IN Placebo + IV morphine (as a standard of care)} procedure, that is an absence of increase rate of hemodynamic and non‐hemodynamic side effects of opiates,f)To evaluate the safety of all children aged 0‐18 years,g)To demonstrate that the {IN Sufentanil +IV morphine (as a standard of care)} procedure, when compared to {IN Placebo + IV morphine (as a standard of care)} procedure, is able to improve the management of a VOC episode,h)To demonstrate that the {IN Sufentanil +IV morphine (as a standard of care)} procedure, when compared to {IN Placebo + IV morphine(as a standard of care)} procedure, is able to decrease the proportion of VOC complications,i)To demonstrate that the {IN Sufentanil +IV morphine(as a standard of care)} procedure, when compared to {IN Placebo + IV morphine (as a standard of care)} procedure, is able to improve parent and child satisfaction with the quality of analgesia and management during the emergency room stay INCLUSION CRITERIA: At inclusion visit • Sickle‐cell disease = Hemoglobin SS or SC or Sß‐thalassemia • Age < 18 years old • Weight > 10 kgs • Registered with the social security scheme (or State Medical Aid ‐ AME) or his/her beneficiaries • Informed consent of the holder (s) of the exercise of parental authority,At randomization visit • Age < 18 years old • Presenting to the ED with vaso‐occlusive crisis: migratory bone pain, which may occur in the limbs, spine, thorax, pelvis, skull; or crisis known as such by the patient. • Severe pain determined at triage, defined as: ‐ EVENDOL = 10/15 in children aged 0‐8 years or ‐ NRS‐11 = 7/10 in children aged 8 years to less than 18 years • Informed consent of the holder (s) of the exercise of parental authority signed at inclusion visit or at randomisation visit