Efficacy of Sublingual Midazolam in Association With Oral Morphine in Children Analgesia After Bone Fracture (MIDAZODOL)

Clinical Randomized Study of Sublingual Midazolam in Association With Morphine by Oral Route in Arm Fracture in Children at the Emergency Children Care

It is a randomized simple-blind monocentric study; the group A will receive oral morphine with placebo and the group B will receive oral morphine with sublingual midazolam. The aim of this study is to show a more important pain decrease in the group taking midazolam versus placebo.

Study Overview

• Status: Completed
• Conditions: Fractures
• Intervention / Treatment: Drug: Midazolam; Drug: Placebo

Detailed Description

Fracture is often responsible of pain in the paediatric emergency department (ED). This pain is very severe and needs effective drugs.

During a study made at the ED of Necker Enfants Malades Hospital, it has been shown that the oral morphine had a limited action on this kind of pain. Therefore it is interesting to increase the analgesia by making a drug association, for example with the midazolam witch is a benzodiazepine with a sedative and anxiolytic action, and which has got the MMA for the intravenous and the intra rectal forms for children older than 6 months.

The intravenous form has some disadvantages like an extra work and an increase of risk of side effects.

That is why the sublingual form seems to be interesting in this context. Even if some studies have shown the benefit of midazolam as a preanesthetic medication given to children scheduled for a surgical procedure, none has shown the interest of sublingual midazolam associated with oral morphine to relieve the pain due to a displaced fracture.

The aim of this study is to show a more important pain decrease in the group taking midazolam versus placebo.

It is a randomized simple-blind monocentric study; the group A will receive oral morphine with placebo and the group B will receive oral morphine with sublingual midazolam . The pain will be quantified thanks to the visual analogical scale (VAS)before and 30 minutes after the drugs administration, and we will try to show a difference of 15 points(on 100) of the VAS at 30 minutes between the two groups.

60 patients aged from 5 to 16 years old and having a displaced fracture will be enrolled in this study which will last 1 year.

Patients having a contra-indication for morphine and midazolam won't be enrolled as patients with femoral fracture which needs a local anaesthesia.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Hopital Necker enfants Malade - Department of Pediatric Emergency

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• children between 5 and 16 years old
• children with a disjoined bone fracture
• children needed oral morphine analgesia
• written informed consent from one or the two parents or legal pad

Exclusion Criteria:

• ASA score > 2
• concomitant administration of oral analgesia (level II WHO classification) less than 6 hours
• concomitant administration of benzodiazepine less than 24 hours

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: 1; Midazolam and morphine	Drug: Midazolam; 0.2 mg/kg of sublingual midazolam and 0.5 mg/kg of morphine
Placebo Comparator: 2; placebo, Nacl 0.9 %, morphine 0.5 mg/kg	Drug: Placebo; placebo at 0.2 mg/kg and morphine 0.5 mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Difference in the measurement of pain analogical scale values at 30 minutes between the two groups	after administration until 120 minutes

Secondary Outcome Measures

Outcome Measure	Time Frame
Pain Analogical scale Values at 15, 30 minutes, 1 hour, 1h30 and 2 hours.	after administration until 120 minutes
Pain Analogical scale Values after the treatment of the fracture	after administration until 120 minutes
Respiratory rate, Oxymetry	after administration until 120 minutes
Conscience (lethargy or irritability)	after administration until 120 minutes
nausea,	after administration until 120 minutes
skin hyperesthesia, rash	after administration until 120 minutes
children cooperation	after surgical procedure

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Gérard CHERON, MD, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Wille-Ledon C, Chappuy H, Giraud C, Treluyer JM, Cheron G. Comparison of a morphine and midazolam combination with morphine alone for paediatric displaced fractures: a randomized study. Acta Paediatr. 2011 Nov;100(11):e203-7. doi: 10.1111/j.1651-2227.2011.02311.x. Epub 2011 May 11.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: December 26, 2006
• First Submitted That Met QC Criteria: December 26, 2006
• First Posted (Estimate): December 27, 2006

Study Record Updates

• Last Update Posted (Estimate): August 28, 2013
• Last Update Submitted That Met QC Criteria: August 27, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: midazolam; children; sublingual; oral morphine; bone fracture; bone fracture with a deformed member
• Additional Relevant MeSH Terms: Wounds and Injuries; Fractures, Bone; 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: P051033

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No