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

Pain Clinical Trial

— MORPHAPAIN  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02477007
• Other study ID #: P130921
• Secondary ID: 2015-001458-14
• Status: Completed
• Phase: Phase 3
• Start date: December 3, 2015
• Est. completion date: November 21, 2018

Study information

• Verified date: January 2019
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 304
• Est. completion date: November 21, 2018
• Est. primary completion date: November 21, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Fractures, Bone
• Long-bone Fractures
• Pain

Intervention

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

Locations

Country	Name	City	State
France	Paediatric emergency Armand Trousseau hospital	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (3)

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. Erratum in: Pediatrics. 2007 Jun;119(6):1271. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Degree of pain measured by the EVENDOL score	To evaluate the degree of pain for children between 2 years and 6 years included : Evendol scale is a validated pain scale for use in the accident and emergency departments on children under 7 years old. Success: children 2-6 years (6 years included) with a pain score Evendol < 5 without additional analgesic treatment at 30 minutes after drug administration (DA)	30 minutes
Primary	Degree of pain measured by the Visual Analog Scale	To evaluate the degree of pain for children between 7 years and 17 years included. Patients will be asked to rate their pain severity on a validated 100 mm horizontal or vertical visual analog scale (VAS) marked "no pain" and "most severe pain" at the low and high ends respectively. A standardized explanation will be given to participating children. Success: children 7-17 years with pain score assessed by Visual Analog Scale (VAS) = 30, without additional analgesic treatment at 30 minutes after drug administration (DA)	30 minutes
Secondary	Degree of pain measured by the EVENDOL score	To evaluate the degree of pain for children between 2 years and 6 years included : Evendol scale is a validated pain scale for use in the accident and emergency departments on children under 7 years old.	after immobilisation
Secondary	Degree of pain measured by the EVENDOL score	To evaluate the degree of pain for children between 2 years and 6 years included : Evendol scale is a validated pain scale for use in the accident and emergency departments on children under 7 years old.	15 minutes
Secondary	Degree of pain measured by the EVENDOL score	To evaluate the degree of pain for children between 2 years and 6 years included : Evendol scale is a validated pain scale for use in the accident and emergency departments on children under 7 years old.	60 minutes
Secondary	Degree of pain measured by the EVENDOL score	To evaluate the degree of pain for children between 2 years and 6 years included : Evendol scale is a validated pain scale for use in the accident and emergency departments on children under 7 years old.	90 minutes
Secondary	Degree of pain measured by the EVENDOL score	To evaluate the degree of pain for children between 2 years and 6 years included : Evendol scale is a validated pain scale for use in the accident and emergency departments on children under 7 years old.	120 minutes
Secondary	Degree of pain measured by the Visual Analog Scale	To evaluate the degree of pain for children between 7 years and 17 years included. Patients will be asked to rate their pain severity on a validated 100 mm horizontal or vertical visual analog scale (VAS) marked "no pain" and "most severe pain" at the low and high ends respectively. A standardized explanation will be given to participating children.	after immobilisation
Secondary	Degree of pain measured by the Visual Analog Scale	To evaluate the degree of pain for children between 7 years and 17 years included. Patients will be asked to rate their pain severity on a validated 100 mm horizontal or vertical visual analog scale (VAS) marked "no pain" and "most severe pain" at the low and high ends respectively. A standardized explanation will be given to participating children.	15 minutes
Secondary	Degree of pain measured by the Visual Analog Scale	To evaluate the degree of pain for children between 7 years and 17 years included. Patients will be asked to rate their pain severity on a validated 100 mm horizontal or vertical visual analog scale (VAS) marked "no pain" and "most severe pain" at the low and high ends respectively. A standardized explanation will be given to participating children.	60 minutes
Secondary	Degree of pain measured by the Visual Analog Scale	To evaluate the degree of pain for children between 7 years and 17 years included. Patients will be asked to rate their pain severity on a validated 100 mm horizontal or vertical visual analog scale (VAS) marked "no pain" and "most severe pain" at the low and high ends respectively. A standardized explanation will be given to participating children.	90 minutes
Secondary	Degree of pain measured by the Visual Analog Scale	To evaluate the degree of pain for children between 7 years and 17 years included. Patients will be asked to rate their pain severity on a validated 100 mm horizontal or vertical visual analog scale (VAS) marked "no pain" and "most severe pain" at the low and high ends respectively. A standardized explanation will be given to participating children.	120 minutes
Secondary	Tolerance of ibuprofen	occurrence of abdominal pain or diarrhea or nausea or vomiting or digestive bleeding or itching or rash.	15 minutes
Secondary	Tolerance of ibuprofen	occurrence of abdominal pain or diarrhea or nausea or vomiting or digestive bleeding or itching or rash.	30 minutes
Secondary	Tolerance of ibuprofen	occurrence of abdominal pain or diarrhea or nausea or vomiting or digestive bleeding or itching or rash.	60 minutes
Secondary	Tolerance of ibuprofen	occurrence of abdominal pain or diarrhea or nausea or vomiting or digestive bleeding or itching or rash.	90 minutes
Secondary	Tolerance of ibuprofen	occurrence of abdominal pain or diarrhea or nausea or vomiting or digestive bleeding or itching or rash.	120 minutes
Secondary	Tolerance of paracetamol	Occurrence of rash or hives or itching or swelling	15 minutes
Secondary	Tolerance of paracetamol	Occurrence of rash or hives or itching or swelling	30 minutes
Secondary	Tolerance of paracetamol	Occurrence of rash or hives or itching or swelling	60 minutes
Secondary	Tolerance of paracetamol	Occurrence of rash or hives or itching or swelling	90 minutes
Secondary	Tolerance of paracetamol	Occurrence of rash or hives or itching or swelling	120 minutes
Secondary	Tolerance of morphine	heart and respiratory rates,	15 minutes
Secondary	Tolerance of morphine	heart and respiratory rates,	30 minutes
Secondary	Tolerance of morphine	heart and respiratory rates,	60 minutes
Secondary	Tolerance of morphine	heart and respiratory rates,	90 minutes
Secondary	Tolerance of morphine	heart and respiratory rates,	120 minutes
Secondary	Tolerance of morphine	oxygen saturation	15 minutes
Secondary	Tolerance of morphine	oxygen saturation	30 minutes
Secondary	Tolerance of morphine	oxygen saturation	60 minutes
Secondary	Tolerance of morphine	oxygen saturation	90 minutes
Secondary	Tolerance of morphine	oxygen saturation	120 minutes
Secondary	Tolerance of morphine	occurrence of consciousness nausea and vomiting or pruritus or drowsiness or dizziness	15 minutes
Secondary	Tolerance of morphine	occurrence of consciousness nausea and vomiting or pruritus or drowsiness or dizziness	30 minutes
Secondary	Tolerance of morphine	occurrence of consciousness nausea and vomiting or pruritus or drowsiness or dizziness	60 minutes
Secondary	Tolerance of morphine	occurrence of consciousness nausea and vomiting or pruritus or drowsiness or dizziness	90 minutes
Secondary	Tolerance of morphine	occurrence of consciousness nausea and vomiting or pruritus or drowsiness or dizziness	120 minutes