Intranasal Midazolam Versus Intranasal Ketamine to Sedate Newborns for Intubation in Delivery Room

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2012 by University Hospital, Montpellier
Sponsor:
Information provided by (Responsible Party):
University Hospital, Montpellier
ClinicalTrials.gov Identifier:
NCT01517828
First received: December 12, 2011
Last updated: May 29, 2012
Last verified: May 2012
  Purpose

Anesthesia is rarely used to intubate newborns in delivery room because of the very difficulty of accessing veins. The investigators hypothesized that intranasal administration of sedative would be an effective alternative. -Midazolam and Ketamine are two drugs used during neonates' intubation. They are also used intranasally in the absence of venous access-In a pilot study the investigators have demonstrated that sedation with Midazolam was effective in 67% of the patients. Efficiency was defined by a specific pain score: FANS < 4 (Faceless Acute Neonatal Pain Scale) and by an impedancemetric Pain monitor < 0.2 spike/s.

The investigators hypothesized that intranasal ketamine would increase procedure effectiveness from 67 to 90%.

  • Main objective: To compare newborns sedation quality as they are sedated either by intranasal Midazolam or by intranasal Ketamine during intubation in delivery room.
  • Secondary Objectives: To compare intubation quality, hemodynamic and respiratory tolerance, and neurological outcomeat 2 years within the two groups.

Condition Intervention Phase
Respiratory Distress Syndrome
Prematurity of Fetus
Drug: Sedation by ketamine
Drug: Sedation with Midazolam
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Intranasal Midazolam Versus Intranasal Ketamine to Sedate Newborns for Intubation in Delivery Room.

Resource links provided by NLM:


Further study details as provided by University Hospital, Montpellier:

Primary Outcome Measures:
  • Newborns sedation quality [ Time Frame: during the 10 minutes of intubation ] [ Designated as safety issue: No ]
    The sedation quality of 2 newborns groups will be compared during the 10 minutes of intubation directly in delivery room and after on the film Pain evaluation done by a Specific clinical Score : the Faceless Acute Neonatal pain Scale (FANS) noted by two independent professional persons. And for Montpellier center, evaluation of pain by cutaneous conductance


Secondary Outcome Measures:
  • intubation quality [ Time Frame: during the 10 minutes of intubation ] [ Designated as safety issue: Yes ]
    Intubation quality will be evaluated and compared between the two groups by numbers of attempts, duration of glottis exposition (from introduction to withdrawal of laryngoscop)

  • hemodynamic and respiratory tolerance [ Time Frame: during 24 hours after intubation ] [ Designated as safety issue: Yes ]

    Hemodynamic tolerance will be measured by Mean Arterial Pressure every 3 minutes before and after product instillation and during the intubation. After intubation, measure of Mean Arterial Pressure will be done every 10 minutes during 1 hour and after every hour until 24 hours. Cardiac frequency and cardiac fraquency variations will be measured and analyzed.

    Respiratory tolerance will be evaluated by continuing measure of SpO2, delay of instillation of surfactant dose and the need to administer un second dose of surfactant


  • neurological outcome at 2 years within the 2 groups [ Time Frame: 2 years after the treatment ] [ Designated as safety issue: Yes ]
    Prevalence of neurological complications (intraventricular hemorragies, periventricular leucomalacies), development quotient at 2 years (Brunet Lezine scale)will be evaluated and compared between the two groups


Estimated Enrollment: 120
Study Start Date: January 2012
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ketamine Arm
Phial of Ketamine (50mg/5ml) will be used and the dose administered will be 2 mg/kg.
Drug: Sedation by ketamine

Kétamine (50mg/5ml, Panpharma): for a posology of 2 mg/kg: dose of 0.2 ml/kg Intranasal administration with a 1 ml syringe. Kétamine is a derivated of phencyclidine with a sedative, anesthesic, analgesic and amnesiant activity. Ketamine keeps also a protective reflex of upper respiratory tracts.

One injection will be done and if after 7 minutes, newborn is not correctly sedated another dose of same product will be done.

Active Comparator: Midazolam Arm
Phials of midazolam (5mg/5ml)will be used and the dose administered will be 0.2 ml/kg.
Drug: Sedation with Midazolam

Midazolam (phyal of 5mg/5ml, Mylan S.A.S.) for a posology of 0.2 mg/kg: dose of 0.2 ml/kg Instillation in intranasal with a syringe of 1 ml. Midazolam is an imidazobenzodiazépine, witj a sedative and hypnotic activity,anxiolytic, anti convulsive and muscle relaxant proprieties.

One injection will be done and if after 7 minutes, newborn is not correctly sedated another dose of same product will be done.


Detailed Description:

Randomized, double blind prospective multicenter study. Patients:-Inclusion criteria: (1) neonates in delivery room (2) Presence of repiratory distress syndrom requiring intubation (Silverman score> 3 and / or FiO2 greater than 30 % in premature infants under 30 weeks and over 40% after 30 weeks (3) hemodynamic stability (mean arterial pressure> 3° percentile)

  • Exclusion criteria: (1) Need for intubation in extreme emergency (pneumothorax, meconium aspiration, congenital diaphragmatic hernia, perinatal asphyxia) (2) Birth in the absence of an independent appraiser (3) mother under general anesthesia.
  • Number of subjects required: 120 patients (60 per group) over a period of two years. This number was calculated to show a difference in sedation effectiveness from 67 to 90% with an alpha risk of 5% and a beta risk of 20%.
  • Study design:

After obtaining parental consent, patients will be randomized in "Midazolam" arm or in "Ketamine" arm . Midazolam (0.2mg/kg = 0.2ml/kg) or Ketamine (2mg/kg = 0.2 ml/kg) are instilled in the nose, using a 1 ml syringe. The gesture will be directed by a physician having yet successfully completed a minimum of 50 intubations. After sedation completion, intubation decision will be taken at the onset of muscle relaxation or on the occurrence of apnea.

  • The clinical pain score will be evaluated on film a posteriori by two independent observers using a scale of hetero pain assessment.-Pain will be evaluated through the study of skin conductance.
  • The quality of intubation will be judged by the number of attempts required and by the duration of glottis exposure.
  • Hemodynamic and respiratory tolerances will be judged by measuring respectively variations in blood pressure, heart rate, FiO2 and the oxygen saturation.

The neurological follow-up will be carried out according to Brunet-Lezine developmental scale at the age of 2 years.

  Eligibility

Ages Eligible for Study:   up to 2 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Neonates in delivery room
  • Presence of respiratory distress syndrom requiring intubation (Silverman score> 3 and / or FiO2 greater than 30 % in premature infants under 30 weeks and over 40% after 30 weeks
  • Hemodynamic stability (mean arterial pressure> 3° percentile)

Exclusion Criteria:

  • Need for intubation in extreme emergency (pneumothorax, meconium aspiration, congenital diaphragmatic hernia, perinatal asphyxia)
  • Birth in the absence of an independent appraiser
  • Mother under general anesthesia
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01517828

Contacts
Contact: Christophe CM MILESI, MD +33 4 67 33 66 09 c-milesi@chu-montpellier.fr

Locations
France
Centre Hospitalier Universitaire Recruiting
Montpellier, France, 34000
Contact: Christophe CM MILESI, MD    +33 4 67 33 66 09    c-milesi@chu-montpellier.fr   
Sub-Investigator: Gilles GC CAMBONIE, PH         
Principal Investigator: Christophe CM MILESI, MD         
Centre Hospitalier Universitaire Not yet recruiting
Nimes, France, 30000
Contact: Jean-Bernard JBM MARIETTE, MD         
Principal Investigator: Jean-Bernard JBM MARIETTE, MD         
Centre Hospitalier Général Not yet recruiting
Perpignan, France, 66000
Contact: Pierre PT THEVENOT, MD         
Principal Investigator: Pierre PT THEVENOT, MD         
Sponsors and Collaborators
University Hospital, Montpellier
Investigators
Principal Investigator: Christophe CM MILESI, MD University Hospital, Montpellier
  More Information

No publications provided

Responsible Party: University Hospital, Montpellier
ClinicalTrials.gov Identifier: NCT01517828     History of Changes
Other Study ID Numbers: UF8736, 2011-003216-23
Study First Received: December 12, 2011
Last Updated: May 29, 2012
Health Authority: France: Afssaps - French Health Products Safety Agency, Committee for the Protection of Personnes

Keywords provided by University Hospital, Montpellier:
Intubation
Delivery room
Sedation
Analgesia

Additional relevant MeSH terms:
Respiratory Distress Syndrome, Newborn
Infant, Newborn, Diseases
Infant, Premature, Diseases
Lung Diseases
Respiration Disorders
Respiratory Tract Diseases
Ketamine
Midazolam
Adjuvants, Anesthesia
Analgesics
Anesthetics
Anesthetics, Dissociative
Anesthetics, General
Anesthetics, Intravenous
Anti-Anxiety Agents
Central Nervous System Agents
Central Nervous System Depressants
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
GABA Agents
GABA Modulators
Hypnotics and Sedatives
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014