Analgesic Efficacy of Morphine Alone or Combined With Paracetamol and/or Ibuprofen for Long-bones Fractures in Children

NCT ID: NCT02477007

Last Updated: 2025-11-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 304 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-03
• Study Completion Date: 2018-11-21

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.

Conditions

Pain; Long-bone Fractures

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ibuprofen+placebo of paracetamol

Patients will receive in addition to morphine (usual care) ibuprofen and placebo of paracetamol

Group Type: EXPERIMENTAL

Ibuprofen

Intervention Type: DRUG

Ibuprofen will be an oral suspension of 20mg/ml. The doses of ibuprofen 10 mg/kg (maximum dose: 400 mg).

Placebo

Intervention Type: DRUG

Placebo will have the closest flavour, smell and aspect to the active substances, respectively paracetamol and ibuprofen. Placebo will be prepared in bottles with a fake label of active substances for a better blinding both for the nurse and the patient. Labels will be hiding by a mask.

Paracetamol + placebo of ibuprofen

Patients will receive in addition to morphine (usual care) paracetamol and placebo of ibuprofen

Group Type: EXPERIMENTAL

Paracetamol

Intervention Type: DRUG

Paracetamol will be an oral solution of 30 mg/ml. The doses of paracetamol will be 15 mg/kg (maximum dose: 1g).

Placebo

Intervention Type: DRUG

Placebo will have the closest flavour, smell and aspect to the active substances, respectively paracetamol and ibuprofen. Placebo will be prepared in bottles with a fake label of active substances for a better blinding both for the nurse and the patient. Labels will be hiding by a mask.

Paracetamol + ibuprofen

Patients will receive in addition to morphine (usual care) paracetamol and ibuprofen

Group Type: EXPERIMENTAL

paracetamol + ibuprofen

Intervention Type: DRUG

Paracetamol will be an oral solution of 30 mg/ml. The doses of paracetamol will be 15 mg/kg (maximum dose: 1g) Ibuprofen will be an oral suspension of 20mg/ml. The doses of ibuprofen 10 mg/kg (maximum dose: 400 mg).

Placebo of paracetamol + placebo of ibuprofen

Patients will receive morphine alone(usual care).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will have the closest flavour, smell and aspect to the active substances, respectively paracetamol and ibuprofen. Placebo will be prepared in bottles with a fake label of active substances for a better blinding both for the nurse and the patient. Labels will be hiding by a mask.

Interventions

Paracetamol

Paracetamol will be an oral solution of 30 mg/ml. The doses of paracetamol will be 15 mg/kg (maximum dose: 1g).

Intervention Type: DRUG

Ibuprofen

Ibuprofen will be an oral suspension of 20mg/ml. The doses of ibuprofen 10 mg/kg (maximum dose: 400 mg).

Intervention Type: DRUG

paracetamol + ibuprofen

Paracetamol will be an oral solution of 30 mg/ml. The doses of paracetamol will be 15 mg/kg (maximum dose: 1g) Ibuprofen will be an oral suspension of 20mg/ml. The doses of ibuprofen 10 mg/kg (maximum dose: 400 mg).

Intervention Type: DRUG

Placebo

Placebo will have the closest flavour, smell and aspect to the active substances, respectively paracetamol and ibuprofen. Placebo will be prepared in bottles with a fake label of active substances for a better blinding both for the nurse and the patient. Labels will be hiding by a mask.

Intervention Type: DRUG

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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hélène Chappuy, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Study Principal Investigator

Locations

Paediatric emergency Armand Trousseau hospital

Paris, , France

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 17332198 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17876251 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10536549 (View on PubMed)

Other Identifiers

2015-001458-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

P130921

Identifier Type: -

Identifier Source: org_study_id