Respiratory Distress SyndromePhase 3NCT01517828
Intranasal Midazolam Versus Intranasal Ketamine to Sedate Newborns for Intubation in Delivery Room
A Phase 3 study testing Sedation by ketamine and Sedation with Midazolam in people with Respiratory Distress Syndrome and Prematurity of Fetus, run by University Hospital, Montpellier at 3 sites in France.
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. Read more about this study
- Who is it for?
- Ages Up to 2 hours
- Conditions the study is for
- Respiratory Distress Syndrome, Prematurity of Fetus
- What is being tested?
- Sedation by ketamine and Sedation with Midazolam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 3 sitesFrance
- Study dates
- Jan 2012to May 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 2 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
France3 sites
Centre Hospitalier Universitaire
Montpellier, 34000
Centre Hospitalier Universitaire
Nîmes, 30000
Centre Hospitalier Général
Perpignan, 66000
About this study
Official title: Intranasal Midazolam Versus Intranasal Ketamine to Sedate Newborns for Intubation in Delivery Room.
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.
Read the 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.
- Being tested
- Sedation by ketamine, Sedation with Midazolam
- Keywords
- Intubation, Delivery room, Sedation, Analgesia
- Medical subject headings
- Respiratory Distress Syndrome, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sedation by ketamineDrug
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 MidazolamDrug
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 group | Role | What they receive |
|---|---|---|
| Ketamine Arm | Experimental | Phial of Ketamine (50mg/5ml) will be used and the dose administered will be 2 mg/kg. Receives: Drug: Sedation by ketamine |
| Midazolam Arm | Active comparator | Phials of midazolam (5mg/5ml)will be used and the dose administered will be 0.2 ml/kg. Receives: Drug: Sedation with Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: during the 10 minutes of intubation
Secondary outcomes (3)
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)
Measured: during the 10 minutes of intubation
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
Measured: during 24 hours after intubation
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
Measured: 2 years after the treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2012 (estimated)
- Study startJan 2012
- Primary completionMay 2016 (estimated)
- Study completionMay 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Respiratory Distress SyndromeStudies of the same condition, open and under way.
- More trials run by University Hospital, MontpellierThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christophe CM MILESI, MD, Principal investigator, University Hospital, Montpellier
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01517828
- Sponsor's protocol ID
- UF8736
- Other IDs
- 2011-003216-23
- Status last verified
- Dec 2014
- First submitted
- 12 Dec 2011
- Last updated
- 3 Dec 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Milesi C, Baleine J, Mura T, Benito-Castro F, Ferragu F, Thiriez G, Thevenot 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.
PubMed 28818854
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intranasal Midazolam Versus Intranasal Ketamine to Sedate Newborns for Intubation in Delivery Room.
- ClinicalTrials.gov ID
- NCT01517828
- Acronym / sponsor ID
- UF8736
- Keywords
- Intubation, Delivery room, Sedation, Analgesia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 62 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Study start
- Jan 2012
- Primary completion
- May 2016 (estimated)
- Study completion
- May 2016 (estimated)
- First posted
- 25 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketamine Arm | Experimental | Drug: Sedation by ketaminePhial of Ketamine (50mg/5ml) will be used and the dose administered will be 2 mg/kg. |
| Midazolam Arm | Active comparator | Drug: Sedation with MidazolamPhials of midazolam (5mg/5ml)will be used and the dose administered will be 0.2 ml/kg. |
Who may qualify
- Ages
- Up to 2 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sedation by ketamineKétamine (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 | Ketamine Arm |
| Sedation with MidazolamMidazolam (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. | Drug | Midazolam Arm |
Primary outcome
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
3 secondary outcomes
intubation quality
Time frame: during the 10 minutes of intubation
hemodynamic and respiratory tolerance
Time frame: during 24 hours after intubation
neurological outcome at 2 years within the 2 groups
Time frame: 2 years after the treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2014.
- Derived from this study: PubMed 28818854Milesi C, Baleine J, Mura T, Benito-Castro F, Ferragu F, Thiriez G, Thevenot 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christophe CM MILESI, MD principal investigator
University Hospital, Montpellier
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sedation by ketamine and Sedation with Midazolam in people with Respiratory Distress Syndrome and Prematurity of Fetus, run by University Hospital, Montpellier at 3 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Newborns sedation quality (time frame: during the 10 minutes of intubation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01517828, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2014.