Trial Outcomes & Findings for Premedication Trial for Tracheal Intubation of the NEOnate (NCT NCT01490580)

NCT ID: NCT01490580

Last Updated: 2021-03-04

Results Overview

Pulse oxymetry value measured by Masimo technology below 80% for 60 seconds or more. Duration of intubation is defined by the time between first laryngoscope insertion and last laryngoscope removal after successful intubation. Successful intubation is defined by clear bilateral breath sounds, increasing heart rate and saturation (if previously low) and appropriate flow curves on the ventilator.

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 173 participants
• Primary outcome timeframe: During intubation procedure, expected duration 1 to 15 minutes
• Results posted on: 2021-03-04

Participant Flow

The trial was prematurely interrupted for logistic reasons in July 2016: a fourth drug manufacturing run was necessary because the intralipids had passed their expiration date and funding had run out. During the study period, 755 patients were screened for eligibility, and 173 randomized

Participant milestones

Measure	Atropine Atracurium Sufentanil n=82 allocated to atropine+atracurium+sufentanil * n=80 received allocated intervention * n=2 did not receive allocated intervention * n=1 never intubated * n=1 received another premedication 82 included in final analysis	Atropine Propofol n=91 allocated to atropine+propofol * n= 2 excluded for lack of consent * n=83 received allocated intervention * n=6 did not receive allocated intervention * n=2 never intubated * n=4 received another premedication 89 included in final analysis
Overall Study STARTED	82	91
Overall Study COMPLETED	82	89
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Measure	Atropine Atracurium Sufentanil n=82 allocated to atropine+atracurium+sufentanil * n=80 received allocated intervention * n=2 did not receive allocated intervention * n=1 never intubated * n=1 received another premedication 82 included in final analysis	Atropine Propofol n=91 allocated to atropine+propofol * n= 2 excluded for lack of consent * n=83 received allocated intervention * n=6 did not receive allocated intervention * n=2 never intubated * n=4 received another premedication 89 included in final analysis
Overall Study Parents withdrew consent	0	2

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Atropine Atracurium Sufentanil n=82 Participants	Atropine Propofol n=89 Participants	Total n=171 Participants Total of all reporting groups
Age, Categorical <=18 years	82 Participants n=82 Participants	89 Participants n=89 Participants	171 Participants n=171 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=82 Participants	0 Participants n=89 Participants	0 Participants n=171 Participants
Age, Categorical >=65 years	0 Participants n=82 Participants	0 Participants n=89 Participants	0 Participants n=171 Participants
Age, Continuous	1 days n=82 Participants	1 days n=89 Participants	1 days n=171 Participants
Sex: Female, Male Female	25 Participants n=82 Participants	45 Participants n=89 Participants	70 Participants n=171 Participants
Sex: Female, Male Male	57 Participants n=82 Participants	44 Participants n=89 Participants	101 Participants n=171 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment France	82 participants n=82 Participants	89 participants n=89 Participants	171 participants n=171 Participants
Median GA at birth [IQR], weeks	29 WEEKS n=82 Participants	30 WEEKS n=89 Participants	29 WEEKS n=171 Participants
Median birth weight [IQR], g	1130 GRAMS n=82 Participants	1310 GRAMS n=89 Participants	1190 GRAMS n=171 Participants
Reason for intubation, n (%) Respiratory distress syndrome	50 Participants n=82 Participants	60 Participants n=89 Participants	110 Participants n=171 Participants
Reason for intubation, n (%) Apnea	9 Participants n=82 Participants	3 Participants n=89 Participants	12 Participants n=171 Participants
Reason for intubation, n (%) Surgery	16 Participants n=82 Participants	20 Participants n=89 Participants	36 Participants n=171 Participants
Reason for intubation, n (%) Other	7 Participants n=82 Participants	6 Participants n=89 Participants	13 Participants n=171 Participants

PRIMARY outcome

Timeframe: During intubation procedure, expected duration 1 to 15 minutes

Pulse oxymetry value measured by Masimo technology below 80% for 60 seconds or more.

Duration of intubation is defined by the time between first laryngoscope insertion and last laryngoscope removal after successful intubation. Successful intubation is defined by clear bilateral breath sounds, increasing heart rate and saturation (if previously low) and appropriate flow curves on the ventilator.

Outcome measures

Measure	Atropine Atracurium Sufentanil n=82 Participants	Atropine Propofol n=89 Participants
Number of Patients With Prolonged Desaturation	54 Participants	53 Participants

SECONDARY outcome

Timeframe: During intubation procedure, expected duration 1 to 15 minutes

Outcome measures

Measure	Atropine Atracurium Sufentanil n=89 Participants	Atropine Propofol n=82 Participants
Number of Intubation Attempts 1 attempt	41 Participants	47 Participants
Number of Intubation Attempts 2 attempts	25 Participants	23 Participants
Number of Intubation Attempts > 2 attempts	21 Participants	11 Participants
Number of Intubation Attempts Missing data	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Expected duration 1 to 15 minutes

Although the initial definition of procedure duration in the registered protocol was the time between the first laryngoscope insertion and last laryngoscope removal after successful intubation, the variable collected in the clinical research form was defined as the time between first laryngoscope insertion and the fixation of the tube with tape.

Outcome measures

Measure	Atropine Atracurium Sufentanil n=84 Participants	Atropine Propofol n=80 Participants
Duration of Intubation Procedure	6.0 Minutes Interval 2.8 to 9.1	3.5 Minutes Interval 1.3 to 6.0

SECONDARY outcome

Timeframe: from 1 minute before to 60 minutes after the start of premedication

Heart rate recordings 1 minute before the first injection and at 3, 6, 9, 12, 15, 30, 45 and 60 minutes after the first injection

Outcome measures

Measure	Atropine Atracurium Sufentanil n=86 Participants	Atropine Propofol n=80 Participants
Heart Rate Heart rate from t-1 to t+6, Difference in bpm	3.3 bpm Standard Deviation 19.5	11.5 bpm Standard Deviation 19.6
Heart Rate Heart rate from t-1 to t+9, Difference in bpm	1.6 bpm Standard Deviation 25.2	11.7 bpm Standard Deviation 25.3

SECONDARY outcome

Timeframe: Within 7 days after inclusion

Worsening of head ultrasound scans in the 7 days after intubation from the preinclusion evaluation, defined as either a normal scan before inclusion and any grade intraventricular hemorrhage (IVH) afterwards, or as a preinclusion grade 1 or 2 IVH scan deteriorating to grade 3 or 4 IVH, according to Papile's classification; This analysis was not centralized but performed in each center according to its usual protocols.

Outcome measures

Measure	Atropine Atracurium Sufentanil n=68 Participants	Atropine Propofol n=68 Participants
Short Term Neurological Outcome: Worsening of Head Ultrasound	14 Participants	12 Participants

SECONDARY outcome

Timeframe: At 2 years corrected age

Population: To handle missing data on ASQ scores, we performed multiple imputation with chained equations using the SAS "MI" procedure. The primary analysis was performed on the imputed dataset in the "as treated" study groups.

Survival without risk of neurodevelopmental delay. Risk of neurodevelopmental delay was defined as no Ages and Stages Questionnaires (ASQ) domain score below threshold (-2 SD) at 2 years of corrected age. The ASQ includes 30 items in 5 neurodevelopmental domains: communication abilities, gross motor skills, fine motor skills, problem solving abilities, and personal-social skills. For each domain, the score obtained by the sum of the items ranges from 0 to 60 and the overall maximum ASQ score is 300 points. For each domain, the score can be categorized using established screening thresholds: an ASQ score <-2 SD below the mean suggests a risk of neurodevelopmental delay in that domai.

Outcome measures

Measure	Atropine Atracurium Sufentanil n=81 Participants	Atropine Propofol n=85 Participants
Number of Patients Surviving Without Ages and Stages Questionnaire Score Below Threshold at Age 2	38 Participants	45 Participants

SECONDARY outcome

Timeframe: from 1 minute before to 60 minutes after the start of premedication

Population: Changes in SpO2 value from baseline were analyzed at predefined time points. Data was missing at some time points.

Pulse oxymetry recordings 1 minute before the first injection and at 3, 6, 9, 12, 15, 30, 45 and 60 minutes after the first injection

Outcome measures

Measure	Atropine Atracurium Sufentanil n=85 Participants	Atropine Propofol n=80 Participants
Pulse Oxymetry SpO2 from t-1 to t+6, Difference in %	-6.0 % SpO2 Standard Deviation 20.1	-12.0 % SpO2 Standard Deviation 20.1
Pulse Oxymetry SpO2 from t-1 to t+9, Difference in %	-8.7 % SpO2 Standard Deviation 22.3	-15.9 % SpO2 Standard Deviation 22.2

SECONDARY outcome

Timeframe: from 1 minute before to 60 minutes after the start of premedication

Population: Changes from baseline in mean arterial blood pressure (MAP) were analyzed at predefined time points. Values were missing at some time points.

Blood pressure recordings 1 minute before the first injection and at 3, 6, 9, 12, 15, 30, 45 and 60 minutes after the first injection

Outcome measures

Measure	Atropine Atracurium Sufentanil n=80 Participants	Atropine Propofol n=77 Participants
Mean Blood Pressure Mean arterial blood pressure from t-1 to t+15	-6.8 Difference in mm Hg Standard Deviation 12.7	0.2 Difference in mm Hg Standard Deviation 12.7
Mean Blood Pressure Mean arterial blood pressure from t-1 to t+30	-9.1 Difference in mm Hg Standard Deviation 9.3	-3.3 Difference in mm Hg Standard Deviation 9.4

SECONDARY outcome

Timeframe: from 1 minute before to 60 minutes after the start of premedication

Population: Changes in TcPCO2 from baseline were analyzed at predefined time points. Values were missing at some time points.

TcPCO2 recordings 1 minute before the first injection and at 3, 6, 9, 12, 15, 30, 45 and 60 minutes after the first injection

Outcome measures

Measure	Atropine Atracurium Sufentanil n=32 Participants	Atropine Propofol n=29 Participants
Transcutaneous PCO2 (TcPCO2) Measurement TcPCO2 from t-1 to t+15	8.0 Difference in mm Hg Standard Deviation 14.4	14.1 Difference in mm Hg Standard Deviation 14.4
Transcutaneous PCO2 (TcPCO2) Measurement TcPCO2 from t-1 to t+30	5.1 Difference in mm Hg Standard Deviation 19.1	16.2 Difference in mm Hg Standard Deviation 19.3

Adverse Events

Atropine + Propofol

Serious events: 9 serious events

Other events: 25 other events

Deaths: 2 deaths

Atropine + Atracurium + Sufentanil

Serious events: 16 serious events

Other events: 28 other events

Deaths: 3 deaths

Serious adverse events

Measure	Atropine + Propofol n=83 participants at risk atropine+ propofol: Atropine bolus: 20 µg/kg Propofol injected over 60 seconds: 1 mg/kg for infants \< 1000g - Renewable once 2.5 mg/kg for infants \> 1000G - Possible additional dose of 1 mg/kg	Atropine + Atracurium + Sufentanil n=80 participants at risk atropine + atracurium + sufentanil: Atropine bolus: 20 µg/kg Atracurium: 0.3 mg/kg- Possible additional dose of 0.1 mg/kg Sufentanil: 0.1 µg/kg for infants \< 1000g 0.2 µg/kg for infants \> 1000g
Respiratory, thoracic and mediastinal disorders Death	2.4% 2/83 • Number of events 2	3.8% 3/80 • Number of events 3
Cardiac disorders Cardiac arrest	1.2% 1/83 • Number of events 1	1.2% 1/80 • Number of events 1
Respiratory, thoracic and mediastinal disorders Thoracic rigidity	3.6% 3/83 • Number of events 3	13.8% 11/80 • Number of events 11
Vascular disorders Hypotension (treated)	2.4% 2/83 • Number of events 2	0.00% 0/80
General disorders OTHER	1.2% 1/83 • Number of events 1	1.2% 1/80 • Number of events 1

Other adverse events

Measure	Atropine + Propofol n=83 participants at risk atropine+ propofol: Atropine bolus: 20 µg/kg Propofol injected over 60 seconds: 1 mg/kg for infants \< 1000g - Renewable once 2.5 mg/kg for infants \> 1000G - Possible additional dose of 1 mg/kg	Atropine + Atracurium + Sufentanil n=80 participants at risk atropine + atracurium + sufentanil: Atropine bolus: 20 µg/kg Atracurium: 0.3 mg/kg- Possible additional dose of 0.1 mg/kg Sufentanil: 0.1 µg/kg for infants \< 1000g 0.2 µg/kg for infants \> 1000g
Vascular disorders Hypotension, not treated	10.8% 9/83 • Number of events 9	1.2% 1/80 • Number of events 1
Vascular disorders Hypertension	8.4% 7/83 • Number of events 7	8.8% 7/80 • Number of events 7
Cardiac disorders Bradycardia	1.2% 1/83 • Number of events 1	7.5% 6/80 • Number of events 6
General disorders Other	14.5% 12/83 • Number of events 12	17.5% 14/80 • Number of events 14

Additional Information

Dr Xavier Durrmeyer

NICU, CHI Créteil

Phone: +33145175433

Email: xavier.durrmeyer@chicreteil.fr

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place