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

Respiratory Distress Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01517828
• Other study ID #: UF8736
• Secondary ID: 2011-003216-23
• Status: Active, not recruiting
• Phase: Phase 3
• First received: December 12, 2011
• Last updated: December 2, 2014
• Start date: January 2012
• Est. completion date: May 2016

Study information

• Verified date: December 2014
• Source: University Hospital, Montpellier
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - French Health Products Safety Agency, Committee for the Protection of Personnes
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 62
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 2 Hours

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prematurity of Fetus
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn

Intervention

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.
• 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.

Locations

Country	Name	City	State
France	Centre Hospitalier Universitaire	Montpellier
France	Centre Hospitalier Universitaire	Nimes
France	Centre Hospitalier Général	Perpignan

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Montpellier

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Newborns sedation quality	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	during the 10 minutes of intubation	No
Secondary	intubation quality	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)	during the 10 minutes of intubation	Yes
Secondary	hemodynamic and respiratory tolerance	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	during 24 hours after intubation	Yes
Secondary	neurological outcome at 2 years within the 2 groups	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	2 years after the treatment	Yes