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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase III Clinical Trial Studying Analgesic Efficacy of Morphine Alone or Combined With Paracetamol and/or Ibuprofen for Long-bones Fractures in Children

Conditions
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Pain, Long-bone Fractures

Intervention / Treatment
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* Drug: Paracetamol
* Drug: Ibuprofen
* Drug: paracetamol + ibuprofen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ibuprofen+placebo of paracetamol<br>Patients will receive in addition to morphine (usual care) ibuprofen and placebo of paracetamol | Drug: Ibuprofen<br>* Ibuprofen will be an oral suspension of 20mg/ml. The doses of ibuprofen 10 mg/kg (maximum dose: 400 mg).<br>Drug: Placebo<br>* 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.<br>|
| Experimental: Paracetamol + placebo of ibuprofen<br>Patients will receive in addition to morphine (usual care) paracetamol and placebo of ibuprofen | Drug: Paracetamol<br>* Paracetamol will be an oral solution of 30 mg/ml. The doses of paracetamol will be 15 mg/kg (maximum dose: 1g).<br>Drug: Placebo<br>* 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.<br>|
| Experimental: Paracetamol + ibuprofen<br>Patients will receive in addition to morphine (usual care) paracetamol and ibuprofen | Drug: paracetamol + ibuprofen<br>* 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).<br>|
| Placebo Comparator: Placebo of paracetamol + placebo of ibuprofen<br>Patients will receive morphine alone(usual care). | Drug: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Tolerance of ibuprofen | occurrence of abdominal pain or diarrhea or nausea or vomiting or digestive bleeding or itching or rash. | 15 minutes | 
| Tolerance of ibuprofen | occurrence of abdominal pain or diarrhea or nausea or vomiting or digestive bleeding or itching or rash. | 30 minutes | 
| Tolerance of ibuprofen | occurrence of abdominal pain or diarrhea or nausea or vomiting or digestive bleeding or itching or rash. | 60 minutes | 
| Tolerance of ibuprofen | occurrence of abdominal pain or diarrhea or nausea or vomiting or digestive bleeding or itching or rash. | 90 minutes | 
| Tolerance of ibuprofen | occurrence of abdominal pain or diarrhea or nausea or vomiting or digestive bleeding or itching or rash. | 120 minutes | 
| Tolerance of paracetamol | Occurrence of rash or hives or itching or swelling | 15 minutes | 
| Tolerance of paracetamol | Occurrence of rash or hives or itching or swelling | 30 minutes | 
| Tolerance of paracetamol | Occurrence of rash or hives or itching or swelling | 60 minutes | 
| Tolerance of paracetamol | Occurrence of rash or hives or itching or swelling | 90 minutes | 
| Tolerance of paracetamol | Occurrence of rash or hives or itching or swelling | 120 minutes | 
| Tolerance of morphine | heart and respiratory rates, | 15 minutes | 
| Tolerance of morphine | heart and respiratory rates, | 30 minutes | 
| Tolerance of morphine | heart and respiratory rates, | 60 minutes | 
| Tolerance of morphine | heart and respiratory rates, | 90 minutes | 
| Tolerance of morphine | heart and respiratory rates, | 120 minutes | 
| Tolerance of morphine | oxygen saturation | 15 minutes | 
| Tolerance of morphine | oxygen saturation | 30 minutes | 
| Tolerance of morphine | oxygen saturation | 60 minutes | 
| Tolerance of morphine | oxygen saturation | 90 minutes | 
| Tolerance of morphine | oxygen saturation | 120 minutes | 
| Tolerance of morphine | occurrence of consciousness nausea and vomiting or pruritus or drowsiness or dizziness | 15 minutes | 
| Tolerance of morphine | occurrence of consciousness nausea and vomiting or pruritus or drowsiness or dizziness | 30 minutes | 
| Tolerance of morphine | occurrence of consciousness nausea and vomiting or pruritus or drowsiness or dizziness | 60 minutes | 
| Tolerance of morphine | occurrence of consciousness nausea and vomiting or pruritus or drowsiness or dizziness | 90 minutes | 
| Tolerance of morphine | occurrence of consciousness nausea and vomiting or pruritus or drowsiness or dizziness | 120 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Paediatric emergency, long-bones fractures, morphine, ibuprofen, paracetamol, children, pain