Clinical Trial Results:
Inhaled Nitric Oxide Gas Therapy in Mechanically Ventilated Patients with Severe Acute Respiratory Syndrome in COVID-19
Summary
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EudraCT number |
2020-001490-68 |
Trial protocol |
SE |
Global end of trial date |
15 Apr 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Jul 2022
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First version publication date |
30 Jul 2022
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
NCT04306393
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04306393 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Danderyd Hospital
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Sponsor organisation address |
Entrévagen 2, Danderyd, Sweden, 18257
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Public contact |
Dept of Medicine and Infection, Danderyd Hospital, +46 8123 550 00, magnus.hedenstierna@regionstockholm.se
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Scientific contact |
Dept of Medicine and Infection, Danderyd Hospital, +46 8123 550 00, magnus.hedenstierna@regionstockholm.se
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Jul 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
15 Apr 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Apr 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective is to measure the difference in ventilator treatment time between the iNO and the control group.
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Protection of trial subjects |
All patients were in ICU on mechanical ventilation sedated and provided analgesia for mechanical controlled ventilation
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Background therapy |
Full ICU therapy | ||
Evidence for comparator |
Pure oxygen to add to the inspired gas mixture | ||
Actual start date of recruitment |
03 May 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Sweden: 40
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Worldwide total number of subjects |
40
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EEA total number of subjects |
40
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
23
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From 65 to 84 years |
17
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients with confirmed COVID-19 infection admitted to Danderyd hospital and in need of mechanical ventilation were included in the study. Recruitment started in may 2020 and ended in january 2021. | |||||||||
Pre-assignment
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Screening details |
All participants were requiered to sign informed consent and therefore screening was performed before intubation/mechanical ventilation. In total 100 subjects were screened for inclusion. Of these 43 never needed mechanical ventilation and were not randomized. Another 17 did not sign informed consent. | |||||||||
Period 1
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Period 1 title |
over all trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Active INO | |||||||||
Arm description |
Inhaled nitric oxide 80 ppm in decreasing dose | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
INOmax
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Medicinal gas, compressed
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Routes of administration |
Respiratory use
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Dosage and administration details |
80 ppm at start and reduced to 40 ppm until hypoxia resolved
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Arm title
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Control | |||||||||
Arm description |
Control O2 | |||||||||
Arm type |
No intervention | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
over all trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Active INO
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Reporting group description |
Inhaled nitric oxide 80 ppm in decreasing dose | ||
Reporting group title |
Control
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Reporting group description |
Control O2 |
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End point title |
duration of mechanical ventilation | |||||||||
End point description |
Days on mechanical ventilation
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End point type |
Primary
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End point timeframe |
During study period
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Attachments |
Time to extubation (F-G Competing risks) |
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Statistical analysis title |
Duration of mechanical ventilation (days) | |||||||||
Comparison groups |
Active INO v Control
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Number of subjects included in analysis |
40
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
= 0.471 | |||||||||
Method |
Fine and Gray competing risks model | |||||||||
Confidence interval |
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End point title |
All cause mortality at 28 days | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
All cause mortality 28 days after randomization
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Attachments |
All cause mortality at 28 days |
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Statistical analysis title |
All cause mortality at 28 days | ||||||||||||
Comparison groups |
Active INO v Control
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Number of subjects included in analysis |
40
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.96 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Cox proportional hazard | ||||||||||||
Point estimate |
1.03
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.38 | ||||||||||||
upper limit |
2.76 |
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Adverse events information [1]
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Timeframe for reporting adverse events |
During study period
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Adverse event reporting additional description |
AEs according to regulations
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
Clinical | |||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
Active
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Reporting group description |
INO | |||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: All patients were ICU treated with mechanical ventilation, sedated, thus it was not possible to separate from the clinical course |
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Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |