Clinical trial NCT02477007: Analgesic Efficacy of Morphine Alone or Combined With Paracetamol and/or Ibuprofen for Long-bones Fractures in Children
Official title: Phase III Clinical Trial Studying Analgesic Efficacy of Morphine Alone or Combined With Paracetamol and/or Ibuprofen for Long-bones Fractures in Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain
Long-bone Fractures
Keywords: Paediatric emergency
pain
long-bones fractures
morphine
ibuprofen
paracetamol
children
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2015-06-22
Enrollment: 304
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The main objective of this study is to evaluate the efficacy of two drugs: paracetamol and ibuprofen in association with morphine, compared with morphine alone on analgesia in children seen in the emergency department for a long-bone fracture and also to study the potential synergic effect of the association paracetamol and ibuprofen.

Detailed description: Long-bone fractures are a very common complain for visits in paediatric emergency departments. Since these fractures are often very painful, morphine is considered the cornerstone treatment in case of severe pain. Very few data are available concerning the assessment of analgesic treatment in this condition. In our previous study, less than 50% of patients with a limb fracture had a Visual Analog Scale (VAS) ≤ 30 mm after morphine administration. Thus, one study make the hypothesis that the use of a combination of morphine and/or paracetamol and/or NSAID could be an effective and safe option for the treatment of pain due to long bone fractures. We undertake to compare different combinations of paracetamol and ibuprofen with morphine to determine the efficacy and safety of these strategies in emergency department paediatric patients with acute traumatic limb pain.

The main objective of this study is to evaluate the efficacy of two drugs: paracetamol and ibuprofen in association with morphine, compared with morphine alone on analgesia in children seen in the emergency department for a long-bone fracture and also to study the potential synergic effect of the association paracetamol and ibuprofen.

Second objectives are

* to compare the long term analgesic efficacy of 4 analgesic regimens a)ibuprofen/morphine, b)paracetamol/morphine, c)ibuprofen/paracetamol/morphine and d)morphine for long bone fracture management in the paediatric emergency department.
* To assess the tolerance of these 4 regimens.

The study is considered as a success if children 2-6 years (6 years included) have a pain score Evendol \< 5 and children 7-17 years (17 years included) have a pain score assessed by Visual Analog Scale (VAS) ≤ 30 without additional analgesic treatment 30 minutes after drug administration.

Eligibility criteria: Inclusion Criteria:

* children aged 2 through 17 years (17 years included)
* suspected fracture of a long bone requiring morphine analgesia (VAS ≥ 60/100 or Evendol ≥ 7/15 at the arrival at emergency department)
* within the first 12 hours after the injury
* at least one signed parental informed consent
* affiliated to health insurance

Exclusion Criteria:

* analgesic treatment within the 6 hours before inclusion
* contraindication to one of the experimental drug: Paracetamol or Ibuprofen
* contraindication to Morphine
* cognitive impairment
* multiple injuries
* resuscitation manœuvres
* suspected femur fracture
* open fracture
* pregnant women in the third trimester

Primary outcomes:
measure: Degree of pain measured by the EVENDOL score
timeFrame: 30 minutes
measure: Degree of pain measured by the Visual Analog Scale
timeFrame: 30 minutes
Secondary outcomes:
measure: Degree of pain measured by the EVENDOL score
timeFrame: after immobilisation
measure: Degree of pain measured by the EVENDOL score
timeFrame: 15 minutes
measure: Degree of pain measured by the EVENDOL score
timeFrame: 60 minutes
measure: Degree of pain measured by the EVENDOL score
timeFrame: 90 minutes
measure: Degree of pain measured by the EVENDOL score
timeFrame: 120 minutes
measure: Degree of pain measured by the Visual Analog Scale
timeFrame: after immobilisation
measure: Degree of pain measured by the Visual Analog Scale
timeFrame: 15 minutes
measure: Degree of pain measured by the Visual Analog Scale
timeFrame: 60 minutes
measure: Degree of pain measured by the Visual Analog Scale
timeFrame: 90 minutes
measure: Degree of pain measured by the Visual Analog Scale
timeFrame: 120 minutes
measure: Tolerance of ibuprofen
timeFrame: 15 minutes
measure: Tolerance of ibuprofen
timeFrame: 30 minutes
measure: Tolerance of ibuprofen
timeFrame: 60 minutes
measure: Tolerance of ibuprofen
timeFrame: 90 minutes
measure: Tolerance of ibuprofen
timeFrame: 120 minutes
measure: Tolerance of paracetamol
timeFrame: 15 minutes
measure: Tolerance of paracetamol
timeFrame: 30 minutes
measure: Tolerance of paracetamol
timeFrame: 60 minutes
measure: Tolerance of paracetamol
timeFrame: 90 minutes
measure: Tolerance of paracetamol
timeFrame: 120 minutes
measure: Tolerance of morphine
timeFrame: 15 minutes
measure: Tolerance of morphine
timeFrame: 30 minutes
measure: Tolerance of morphine
timeFrame: 60 minutes
measure: Tolerance of morphine
timeFrame: 90 minutes
measure: Tolerance of morphine
timeFrame: 120 minutes
measure: Tolerance of morphine
timeFrame: 15 minutes
measure: Tolerance of morphine
timeFrame: 30 minutes
measure: Tolerance of morphine
timeFrame: 60 minutes
measure: Tolerance of morphine
timeFrame: 90 minutes
measure: Tolerance of morphine
timeFrame: 120 minutes
measure: Tolerance of morphine
timeFrame: 15 minutes
measure: Tolerance of morphine
timeFrame: 30 minutes
measure: Tolerance of morphine
timeFrame: 60 minutes
measure: Tolerance of morphine
timeFrame: 90 minutes
measure: Tolerance of morphine
timeFrame: 120 minutes
Other outcomes:
Locations:
city: Paris
country: France
facility: Paediatric emergency Armand Trousseau hospital
Study officials:
affiliation: Study Principal Investigator
name: Hélène Chappuy, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Clark E, Plint AC, Correll R, Gaboury I, Passi B. A randomized, controlled trial of acetaminophen, ibuprofen, and codeine for acute pain relief in children with musculoskeletal trauma. Pediatrics. 2007 Mar;119(3):460-7. doi: 10.1542/peds.2006-1347.
citation: Koller DM, Myers AB, Lorenz D, Godambe SA. Effectiveness of oxycodone, ibuprofen, or the combination in the initial management of orthopedic injury-related pain in children. Pediatr Emerg Care. 2007 Sep;23(9):627-33. doi: 10.1097/PEC.0b013e31814a6a39.
citation: Morton NS, O'Brien K. Analgesic efficacy of paracetamol and diclofenac in children receiving PCA morphine. Br J Anaesth. 1999 May;82(5):715-7. doi: 10.1093/bja/82.5.715.