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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Traumatic Pain
• Intervention / Treatment: Drug: Midazolam

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Brest, France, 29609
    • CHU de Brest
  • Carhaix, France, 29270
    • CH de Carhaix
  • Nantes, France, 44000
    • CHU de NANTES
  • Quimper, France, 29000
    • Centre Hpistalier Intercommunal de Cornouaille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Midazolam; Midazolam (Hypnovel) at 0.04 mg /kg with morphine titration (first bolus: 0.1 mg/kg then 3 mg every 5 minutes).	Drug: Midazolam; Midazolam (Hypnovel) at 0.04 mg /kg with morphine titration (first bolus: 0.1 mg/kg then 3 mg every 5 minutes).; Other Names: Midazolam (hypnovel)
Placebo Comparator: Placebo; 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?

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier de Cornouaille
• Collaborators: Ministry of Health, France
• Investigators: Principal Investigator: Yannick AUFFRET, Dr, Centre Hospitalier Intercommunal de Cornouaille

Publications and helpful links

General Publications

• Auffret Y, Gouillou M, Jacob GR, Robin M, Jenvrin J, Soufflet F, Alavi Z. Does midazolam enhance pain control in prehospital management of traumatic severe pain? Am J Emerg Med. 2014 Jun;32(6):655-9. doi: 10.1016/j.ajem.2014.01.048. Epub 2014 Feb 4.

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: November 13, 2012
• First Submitted That Met QC Criteria: November 16, 2012
• First Posted (Estimate): November 21, 2012

Study Record Updates

• Last Update Posted (Estimate): November 21, 2012
• Last Update Submitted That Met QC Criteria: November 16, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: acute traumatic pain, pre-hospital setting, Midazolam
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: Morphine Midazolam