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

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ClinicalTrials.gov Identifier: NCT01517828
Recruitment Status : Unknown
Verified December 2014 by University Hospital, Montpellier.
Recruitment status was:  Active, not recruiting
First Posted : January 25, 2012
Last Update Posted : December 3, 2014
Sponsor:
Information provided by (Responsible Party):
University Hospital, Montpellier

Tracking Information
First Submitted Date  ICMJE December 12, 2011
First Posted Date  ICMJE January 25, 2012
Last Update Posted Date December 3, 2014
Study Start Date  ICMJE January 2012
Estimated Primary Completion Date May 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 20, 2012)
Newborns sedation quality [ Time Frame: during the 10 minutes of intubation ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 20, 2012)
  • intubation quality [ Time Frame: during the 10 minutes of intubation ]
    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 ]
    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 ]
    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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intranasal Midazolam Versus Intranasal Ketamine to Sedate Newborns for Intubation in Delivery Room
Official Title  ICMJE Intranasal Midazolam Versus Intranasal Ketamine to Sedate Newborns for Intubation in Delivery Room.
Brief Summary

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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Respiratory Distress Syndrome
  • Prematurity of Fetus
Intervention  ICMJE
  • 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.

  • 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.

Study Arms  ICMJE
  • Experimental: Ketamine Arm
    Phial of Ketamine (50mg/5ml) will be used and the dose administered will be 2 mg/kg.
    Intervention: Drug: Sedation by ketamine
  • Active Comparator: Midazolam Arm
    Phials of midazolam (5mg/5ml)will be used and the dose administered will be 0.2 ml/kg.
    Intervention: Drug: Sedation with Midazolam
Publications * Milési C, Baleine J, Mura T, Benito-Castro F, Ferragu F, Thiriez G, Thévenot P, Combes C, Carbajal R, Cambonie G. Nasal midazolam vs ketamine for neonatal intubation in the delivery room: a randomised trial. Arch Dis Child Fetal Neonatal Ed. 2018 May;103(3):F221-F226. doi: 10.1136/archdischild-2017-312808. Epub 2017 Aug 17.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Actual Enrollment  ICMJE
 (submitted: December 2, 2014)
62
Original Estimated Enrollment  ICMJE
 (submitted: January 20, 2012)
120
Estimated Study Completion Date  ICMJE May 2016
Estimated Primary Completion Date May 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 2 Hours   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01517828
Other Study ID Numbers  ICMJE UF8736
2011-003216-23 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Hospital, Montpellier
Study Sponsor  ICMJE University Hospital, Montpellier
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Christophe CM MILESI, MD University Hospital, Montpellier
PRS Account University Hospital, Montpellier
Verification Date December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP