Non-invasive Neurally Adjusted Ventilatory Assist Versus Nasal Intermittent Positive Pressure Ventilation for Preterm Infants After Extubation: A Randomised Control Trial
Phase: NA
Conditions: Prematurity, Respiratory Failure, Ventilator Lung; Newborn
Sponsor: King Fahad Armed Forces Hospital

 
1 
COVER PAGE 
Official Title: NON-INVASIVE NEURALLY ADJUSTED VENTILATORY ASSIST VERSUS 
NASAL INTERMITTENT POSITIVE PRESSURE VENTILATION FOR PRETERM INFANTS 
AFTER EXTUBATION: A RANDOMIZED CONTROLLED TRIAL  
NCT number: NCT03388437 
Document Date: 31/05/2021 
 

 
2 
Study Results 
Study Type 
Interventional 
Study Design 
Allocation: Randomized;   Intervention Model: Parallel Assignment;   
Masking: None (Open Label);   Primary Purpose: Treatment 
Condition 
Non-invasive neurally adjusted ventilatory assist versus nasal 
intermittent positive pressure ventilation for preterm infants after 
extubation 
Intervention 
Device: noninvasive respiratory support with NAVA mode and NIPPV 
Enrollment 
36 
 
 
 

 
3 
Participant Flow 
Recruitment Details 
 Patients recruited from single tertiary center neonatal intensive care 
unit (NICU) level 3 at the King Fahad Armed Forces Hospital  
in Saudi Arabia between May 2017 and April 2019 
Pre-assignment Details  41 assessed for eligibility, 5 excluded, 36 randomized subsequently 
equally  
Arm/Group Title 
NI-NAVA 
NIPPV 
Arm/Group Description 
NI-NAVA after extubation  
Initial ventilatory settings 
were NAVA level of 2; 
Positive 
End 
Expiratory 
Pressure (PEEP) of 5-6 cm 
H2O; 
apnea 
time 
5-10 
seconds; and target electrical 
activity of the diaphragm 
(Edi) maximum between 10-
15 and minimum <5 for 72 
hours post extubation. 
NIPPV after extubation 
Positive Inspiratory Pressure (PIP) 
incremented at 2 cm H2O from the 
pre-extubation PEEP of 5-6 cm H20 
for 72 hours post extubation. The set 
respiratory rate was same as prior to 
extubation. 
Period Title: Overall Study 
Started 
18 
18 
Completed 
18 
18 
Not Completed 
0 
0 
Reason Not Completed 
Adverse Event (Death) 
2 
1  
 
 
 

 
4 
Baseline Characteristics 
Arm/Group Title 
NI-NAVA 
Group 
NIPPV Group 
Total 
 Arm/Group Description Non-invasive 
Neurally 
adjusted 
ventilatory assist 
(NAVA) after 
extubation in 
preterm infants 
Non-invasive 
positive pressure 
ventilation 
(NIPPV) after 
extubation in 
preterm infants 
Total of all 
reporting 
groups 
Overall Number of Baseline 
Participants 
18 
18 
36 
 Baseline Analysis Population 
Description 
[Not Specified] 
Age at extubation, 
Continuous   
Mean (Standard 
deviation) 
Unit of measure:  Days 
 
 
 
 
 
Number 
Analyzed 
18 participants 
18 participants 
36 
participants 
 
1.67 (1.49)  
1.17 (0.38)  
 
1.41(1.11) 
Sex: Female, Male   
 
 
 
 

 
5 
Measure Type: Count of 
Participants 
Unit of 
measure:  Participants 
 
Number 
Analyzed 
18 participants 
18 participants 
36 
participants 
Female 
8 
  44.4% 
8 
   44.4% 
16 
  44.4% 
Male 
10 
  55.6% 
10 
 55.6% 
20 
  55.6%% 
Gestational Age, 
continuous   
Mean (Standard 
Deviation) 
Unit of measure:  Weeks 
Number 
Analyzed 
18 participants 
18 participants 
36 
participants 
28.94 (1.83) 
28.55 (1.18) 
28.74  (1.53) 
Birth Weight, 
continuous   
Mean (Standard 
deviation) 
 
 
 
 

 
6 
Unit of measure:  g 
 
Number 
Analyzed 
18 participants 
18 participants 
36 
participants 
 
1251.94 (329.13) 
1051.0 (376.99) 
1151.47 
(363.36) 
Antenatal Steroid usage 
Measure Type: Count of 
Participants 
Unit of 
measure:  Frequency 
 
 
 
 
Number 
Analyzed 
18 participants 
18 participants 
36 
participants 
YES 
14 (77.8%) 
11 (61.1%) 
25 (69.4%) 
Presence of IUGR 
Measure Type: Count of 
Participants 
Unit of 
measure:  Frequency 
 
 
 
 
 
Number 
Analyzed 
18 participants 
18 participants 
36 
participants 
 
0 (0%) 
1 (5.6%) 
1 (2.8%) 
CRIB Score 
 
 
 
 

 
7 
Mean (Standard 
Deviation) 
Unit of 
measure:  number 
 
Number 
Analyzed 
18 participants 
18 participants 
36 
participants 
 
1.72 (2.02) 
1.88 (1.40) 
1.80 (1.72) 
Duration of invasive 
ventilation    
Mean (Standard 
Deviation) 
Unit of measure: hours 
 
 
 
 
 
Number 
Analyzed 
18 participants 
18 participants 
36 
participants 
 
22.77 (35.05) 
10.22 (11.55) 
16.50 (26.49) 
Caffeine usage 
Measure Type: Count of 
Participants 
Unit of 
measure:  Participants 
 
 
 
 
 
Number 
Analyzed 
18 participants 
18 participants 
36 
participants 

 
8 
YES 
18 (100%) 
18 (100%) 
36 (100%) 
Patent Ductus Arteriosus 
(PDA) at birth 
Measure Type: Count of 
Participants 
Unit of 
measure:  Participants 
 
 
 
 
 
Number 
Analyzed 
18 participants 
18 participants 
36 
participants 
Present 
7 (38.9%) 
4 (22.2%) 
11 (30.6%) 
  
 
 

 
9 
Outcome Measures 
1. Primary Outcome 
Title 
Treatment failure 
Description 
hypoxia (FiO2 requirement >0.35), respiratory acidosis (pH < 7.2 & PCO 2 
> 60 mm Hg) or major apnea requiring mask ventilation or >4 episodes/hour. 
Rescue treatment with NIPPV was also considered as treatment failure. 
Time Frame 
72 hours 
 
Outcome Measure Data 
• Analysis Population Description 
The analysis was "per protocol". 36 patients who had completed the study was used for the 
analysis. 
Arm/Group Title 
NI-NAVA 
NIPPV 
Arm/Group Description: 
Non-invasive Neurally adjusted 
ventilatory assist (NAVA) after 
extubation in preterm infants 
Non-invasive 
positive 
pressure ventilation (NIPPV) 
after extubation in preterm 
infants 
Overall 
Number 
of 
Participants Analyzed 
18 
18 
Measure Type: Count of 
Participants 
Unit 
of 
measure:  Participants 
 
 
 
1 (5.5%) 
0 (0%) 
 

 
10 
Statistical Analysis 1 
Statistical Analysis Overview Comparison Group Selection NI-NAVA, NIPPV 
Comments 
[Not Specified] 
Type of Statistical Test 
Superiority or Other 
Comments 
[Not Specified] 
Statistical Test of Hypothesis P-Value 
0.310 
Comments 
[Not Specified] 
Method 
Pearson’s chi-square 
Comments 
[Not Specified] 
Method of Estimation 
Estimation Parameter 
 
Estimated Value 
 
Confidence Interval 
 
Parameter Dispersion 
 
Estimation Comments 
 
 
2. Primary Outcome 
Title 
Reintubation 
Description 
Treatment failure leading to reintubation of infant within 72 hours 
Time Frame 
72 hours 
 
Outcome Measure Data 
• Analysis Population Description 

 
11 
The analysis was "per protocol". 36 patients who had completed the study was used for the 
analysis. 
Arm/Group Title 
NI-NAVA 
NIPPV 
Arm/Group Description: 
Non-invasive Neurally adjusted 
ventilatory assist (NAVA) after 
extubation in preterm infants 
Non-invasive 
positive 
pressure ventilation (NIPPV) 
after extubation in preterm 
infants 
Overall 
Number 
of 
Participants Analyzed 
18 
18 
Measure Type: Count of 
Participants 
Unit 
of 
measure:  Participants 
 
 
4 (22.2%) 
2 (11.1%) 
 
Statistical Analysis 1 
Statistical Analysis Overview Comparison Group Selection NI-NAVA, NIPPV 
Comments 
[Not Specified] 
Type of Statistical Test 
Superiority or Other 
Comments 
[Not Specified] 
Statistical Test of Hypothesis P-Value 
0.371 
Comments 
[Not Specified] 
Method 
Pearson’s chi-square 
Comments 
[Not Specified] 

 
12 
Method of Estimation 
Estimation Parameter 
 
Estimated Value 
 
Confidence Interval 
 
Parameter Dispersion 
 
Estimation Comments 
 
 
3. Secondary Outcome 
Title 
Intraventricular Hemorrhage 
Description 
IVH (grades III & IV) classified according to Papile et al after evaluation of 
head ultrasound by a pediatric radiologist 
Time Frame 
72 hours 
 
Outcome Measure Data 
• Analysis Population Description 
The analysis was "per protocol". 36 patients who had completed the study was used for the 
analysis. 
Arm/Group Title 
NI-NAVA 
NIPPV 
Arm/Group Description: 
Non-invasive Neurally adjusted 
ventilatory assist (NAVA) after 
extubation in preterm infants 
Non-invasive 
positive 
pressure ventilation (NIPPV) 
after extubation in preterm 
infants 
Overall 
Number 
of 
Participants Analyzed 
18 
18 

 
13 
Measure Type: Count of 
Participants 
Unit 
of 
measure:  Participants 
 
2 (11.1%) 
0 (0%) 
 
Statistical Analysis 1 
Statistical Analysis Overview Comparison Group Selection NI-NAVA, NIPPV 
Comments 
[Not Specified] 
Type of Statistical Test 
Superiority or Other 
Comments 
[Not Specified] 
Statistical Test of Hypothesis P-Value 
0.486 
Comments 
[Not Specified] 
Method 
Fisher’s exact  
Comments 
[Not Specified] 
Method of Estimation 
Estimation Parameter 
 
Estimated Value 
 
Confidence Interval 
 
Parameter Dispersion 
 
Estimation Comments 
 
 
4. Secondary Outcome 

 
14 
Title 
Necrotizing Enterocolitis 
Description 
Necrotizing enterocolitis defined according to modified Bell's criteria (stage 
2 to 3) 
Time Frame 
72 hours 
 
Outcome Measure Data 
• Analysis Population Description 
The analysis was "per protocol". 36 patients who had completed the study was used for the 
analysis. 
Arm/Group Title 
NI-NAVA 
NIPPV 
Arm/Group Description: 
Non-invasive Neurally adjusted 
ventilatory assist (NAVA) after 
extubation in preterm infants 
Non-invasive 
positive 
pressure ventilation (NIPPV) 
after extubation in preterm 
infants 
Overall 
Number 
of 
Participants Analyzed 
18 
18 
Measure Type: Count of 
Participants 
Unit 
of 
measure:  Participants 
 
 
 
4 (22.2%) 
0 (0%) 
 
Statistical Analysis 1 
Statistical Analysis Overview Comparison Group Selection NI-NAVA, NIPPV 

 
15 
Comments 
[Not Specified] 
Type of Statistical Test 
Superiority or Other 
Comments 
[Not Specified] 
Statistical Test of Hypothesis P-Value 
0.034 
Comments 
[Not Specified] 
Method 
Pearson’s chi-square 
Comments 
[Not Specified] 
Method of Estimation 
Estimation Parameter 
 
Estimated Value 
 
Confidence Interval 
 
Parameter Dispersion 
 
Estimation Comments 
 
 
5. Secondary Outcome 
Title 
Pneumothorax 
Description 
Air leak within pleural cavity diagnosed radiologically 
Time Frame 
72 hours 
 
Outcome Measure Data 
• Analysis Population Description 
The analysis was "per protocol". 36 patients who had completed the study was used for the 
analysis. 

 
16 
Arm/Group Title 
NI-NAVA 
NIPPV 
Arm/Group Description: 
Non-invasive Neurally adjusted 
ventilatory assist (NAVA) after 
extubation in preterm infants 
Non-invasive 
positive 
pressure ventilation (NIPPV) 
after extubation in preterm 
infants 
Overall 
Number 
of 
Participants Analyzed 
18 
18 
Measure Type: Count of 
Participants 
Unit 
of 
measure:  Participants 
 
 
 
0 (0%) 
0 (0%) 
 
Statistical Analysis 1 
Statistical Analysis Overview Comparison Group Selection NI-NAVA, NIPPV 
Comments 
[Not Specified] 
Type of Statistical Test 
Superiority or Other 
Comments 
[Not Specified] 
Statistical Test of Hypothesis P-Value 
- 
Comments 
[Not Specified] 
Method 
- 
Comments 
[Not Specified] 
Method of Estimation 
Estimation Parameter 
 
Estimated Value 
 

 
17 
Confidence Interval 
 
Parameter Dispersion 
 
Estimation Comments 
 
 
6. Secondary Outcome 
Title 
GI Perforation 
Description 
Gastrointestinal perforation diagnosed radiologically or at operation 
Time Frame 
72 hours 
 
Outcome Measure Data 
• Analysis Population Description 
The analysis was "per protocol". 36 patients who had completed the study was used for the 
analysis. 
Arm/Group Title 
NI-NAVA 
NIPPV 
Arm/Group Description: 
Non-invasive Neurally adjusted 
ventilatory assist (NAVA) after 
extubation in preterm infants 
Non-invasive 
positive 
pressure ventilation (NIPPV) 
after extubation in preterm 
infants 
Overall 
Number 
of 
Participants Analyzed 
18 
18 
Measure Type: Count of 
Participants 
Unit 
of 
measure:  Participants 
 
 

 
18 
1 (5.6%) 
0 (0%) 
 
Statistical Analysis 1 
Statistical Analysis Overview Comparison Group Selection NI-NAVA, NIPPV 
Comments 
[Not Specified] 
Type of Statistical Test 
Superiority or Other 
Comments 
[Not Specified] 
Statistical Test of Hypothesis P-Value 
0.310 
Comments 
[Not Specified] 
Method 
Pearson’s chi-square 
Comments 
[Not Specified] 
Method of Estimation 
Estimation Parameter 
 
Estimated Value 
 
Confidence Interval 
 
Parameter Dispersion 
 
Estimation Comments 
 
 
7. Secondary Outcome 
Title 
Sepsis 
Description 
Nosocomial sepsis defined as presence of clinical signs of sepsis or positive 
blood or cerebrospinal fluid (CSF) cultures taken after five days of age 
Time Frame 
72 hours 

 
19 
 
Outcome Measure Data 
• Analysis Population Description 
The analysis was "per protocol". 36 patients who had completed the study was used for the 
analysis. 
Arm/Group Title 
NI-NAVA 
NIPPV 
Arm/Group Description: 
Non-invasive Neurally adjusted 
ventilatory assist (NAVA) after 
extubation in preterm infants 
Non-invasive 
positive 
pressure ventilation (NIPPV) 
after extubation in preterm 
infants 
Overall 
Number 
of 
Participants Analyzed 
18 
18 
Measure Type: Count of 
Participants 
Unit 
of 
measure:  Participants 
 
 
 
2 (11.1%) 
2 (11.1%) 
 
Statistical Analysis 1 
Statistical Analysis Overview Comparison Group Selection NI-NAVA, NIPPV 
Comments 
[Not Specified] 
Type of Statistical Test 
Superiority or Other 
Comments 
[Not Specified] 
Statistical Test of Hypothesis P-Value 
1.000 

 
20 
Comments 
[Not Specified] 
Method 
Pearson’s chi-square 
Comments 
[Not Specified] 
Method of Estimation 
Estimation Parameter 
 
Estimated Value 
 
Confidence Interval 
 
Parameter Dispersion 
 
Estimation Comments 
 
 
8. Secondary Outcome 
Title 
Retinopathy of prematurity 
Description 
Retinopathy of prematurity (ROP) stage 3 or greater according to 
International classification 
Time Frame 
72 hours 
 
Outcome Measure Data 
• Analysis Population Description 
The analysis was "per protocol". 36 patients who had completed the study was used for the 
analysis. 
Arm/Group Title 
NI-NAVA 
NIPPV 
Arm/Group Description: 
Non-invasive Neurally adjusted 
ventilatory assist (NAVA) after 
extubation in preterm infants 
Non-invasive 
positive 
pressure ventilation (NIPPV) 

 
21 
after extubation in preterm 
infants 
Overall 
Number 
of 
Participants Analyzed 
18 
18 
Measure Type: Count of 
Participants 
Unit 
of 
measure:  Participants 
 
 
2 (11.1%) 
1 (5.6%) 
 
Statistical Analysis 1 
Statistical Analysis Overview Comparison Group Selection NI-NAVA, NIPPV 
Comments 
[Not Specified] 
Type of Statistical Test 
Superiority or Other 
Comments 
[Not Specified] 
Statistical Test of Hypothesis P-Value 
0.546 
Comments 
[Not Specified] 
Method 
Pearson’s chi-square 
Comments 
[Not Specified] 
Method of Estimation 
Estimation Parameter 
 
Estimated Value 
 
Confidence Interval 
 
Parameter Dispersion 
 

 
22 
Estimation Comments 
 
 
 
 

 
23 
Adverse Events 
Time Frame 
72 hours 
Adverse 
Event 
Reporting 
Description 
[Not Specified] 
  
Arm/Group Title 
NI-NAVA 
NIPPV 
Arm/Group 
Description 
Non-invasive Neurally adjusted 
ventilatory assist (NAVA) after 
extubation in preterm infants 
Non-invasive 
positive 
pressure 
ventilation (NIPPV) after extubation 
in preterm infants 
All-Cause Mortality  
 
NI-NAVA 
NIPPV 
 
 
Affected / at Risk (%) 
Affected / at Risk (%) 
 
Total  
 2/18 (11.1%) 
 1/18 (5.6%)  
 
Serious Adverse Events  
 
NI-NAVA 
NIPPV 
 
 
Affected / at Risk (%) 
Affected / at Risk (%) 
 
Total  
 0/18 (0.00%)  
 0/18 (0.00%)  
 
 Other (Not Including Serious) Adverse Events  
Frequency 
Threshold 
for Reporting Other 
Adverse Events 
5% 
 
NI-NAVA 
NIPPV 
 
Affected / at Risk (%) 
Affected / at Risk (%) 

 
24 
Total  
 0/18 (0.00%)  
 0/18 (0.00%)  
 
 
 

 
25