Morphine-Midazolam in Pre-hospital Traumatic Patients With Severe Acute Pain

Study Overview
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Brief Summary
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Administration of midazolam with morphine in patients with severe acute pain is a routine practice in the management of pre- and post-operative patients but has not been evaluated in pre-hospital setting. The investigators aim to evaluate the co-analgesic effect of midazolam in the pre-hospital management of traumatic patients with severe acute pain. In a multicenter prospective randomized double-blind placebo-controlled trial, the investigators would like to compare the analgesic effect and safety of the intravenous morphine 0.10 mg/kg and midazolam 0.04 mg/kg with the intravenous morphine 0.10 mg/kg and placebo in pre-hospital traumatic adults. Assessment will be done at the baseline using a validated numeric rating scale (NRS). The primary outcome will be the proportion of patients with a pain score less than or equal to 3 after 20 minutes. The secondary outcomes will be in between-group comparison of: the treatment safety, pain score every 5 minutes during 30 minutes and the total morphine dose required until obtaining a pain score less than or equal to 3.

Detailed Description
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Patient will be included in pre-hospital setting. They must have an acute pain NRS greater than or equal to 6 from a traumatic origin. The participation of the study for each patient will be the time of the pre-hospital setting. The study will stop when the patient arrives at the hospital. Patient will be randomized after obtaining an informed consent. Then, the nurse will administered intravenous morphine 0.10 mg/kg and midazolam 0.04 mg/kg or intravenous morphine 0.10 mg/kg and placebo. Only the nurse will be aware of the treatment received by the patient. Every 5 minutes, life constants and pain score will be recorded on the case report form. Assessment will be done at the baseline using a validated numeric rating scale. The primary outcome will be the proportion of patients with a pain score less than or equal to 3 after 20 minutes. The secondary outcomes will be in between-group comparison of: the treatment safety, pain score every 5 minutes during 30 minutes and the total morphine dose required until obtaining a pain score less than or equal to 3.

Official Title
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Randomized Double-blind Placebo-controlled Trial: Administration of Morphine-Placebo vs. Morphine-Midazolam in Pre-hospital Traumatic Patients With Severe Acute Pain.

Conditions
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Acute Traumatic Pain

Intervention / Treatment
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* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 70 years old conscient with spontaneous ventilation acute pain with an traumatic origin : pain escape superior or egal to 6/10 taking care by French reanimation and urgency mobile services (Smur). Exclusion Criteria: younger than 18 years old or older than 70 years old chronical respiratory insufficiency severe hepatocellular insufficiency, myasthenia known allergy to morphine or benzodiazepin, already treated for a chronical pain, pregnant women treated by morphine patient unable to evaluate his/her pain any acute and severe hemodynamic, respiratory or neurologic deficiency needed an local analgesia patient who received an other antalgic treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Midazolam<br>Midazolam (Hypnovel) at 0.04 mg /kg with morphine titration (first bolus: 0.1 mg/kg then 3 mg every 5 minutes). | Drug: Midazolam<br>* Midazolam (Hypnovel) at 0.04 mg /kg with morphine titration (first bolus: 0.1 mg/kg then 3 mg every 5 minutes).<br>* Other names: Midazolam (hypnovel);|
| Placebo Comparator: Placebo<br>Placebo at 0.04 mg /kg with morphine titration (first bolus: 0.1 mg/kg then 3 mg every 5 minutes). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain score | The primary outcome was the proportion of patients with a pain score less than or equal to 3 after 20 minutes | 20 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pain evolution | The secondary outcomes were in between-group comparison of: - pain score every 5 minutes during 30 minutes | every 5 minutes and at the end of the study | 
| Safety | The secondary outcomes were in between-group comparison of: - The treatment safety | during all the study | 
| Morphine total dose | The secondary outcomes were in between-group comparison of: - The total morphine dose required until obtaining pain score less than or equal to 3 | During all the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute traumatic pain, pre-hospital setting, Midazolam