Clinical Trial Results:
Effect of Supplemental Oxygen on Perioperative Brain Natriuretic Peptide Concentration in Cardiac Risk Patients -
A prospective randomized clinical trial
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Summary
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EudraCT number |
2017-003714-68 |
Trial protocol |
AT |
Global end of trial date |
31 Jan 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Mar 2022
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First version publication date |
01 Mar 2022
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Other versions |
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Summary report(s) |
Publication |
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 |
1744/2017
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03366857 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Medical University of Vienna
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Sponsor organisation address |
Spitalgasse 23, Vienna, Austria, 1090
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Public contact |
Head Office, Department for Anaesthesia, Office Care and Pain Management, 0043 (0) 140400 41020, sekretariat-anaesthesie@meduniwien.ac.at
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Scientific contact |
Head Office, Department for Anaesthesia, Office Care and Pain Management, 0043 (0) 140400 41020, sekretariat-anaesthesie@meduniwien.ac.at
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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 |
12 May 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
15 Dec 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Jan 2020
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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 |
Due to the significant reduction of BNP by inhibiting sympathic nerve activity we hypothesize that supplemental oxygen have beneficial effects in perioperative BNP release in cardiac risk patients undergoing major abdominal surgery.
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Protection of trial subjects |
Patients received randomly assigned 80% versus 30% inspired oxygen concentration throughout surgery and for the first two postoperative hours. We continuously measured peripheral oxygen saturation and measured blood gas analysis hourly. In the case 30% oxygen concentration was not enough, which was defined as peripheral oxygen saturation lower than 93%, we stepwise increased oxygen contraction, to provide sufficient oxygen saturation.
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Background therapy |
Perioperative treatment was performed according to clinical standard of care. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Dec 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Austria: 260
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Worldwide total number of subjects |
260
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EEA total number of subjects |
260
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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) |
41
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From 65 to 84 years |
203
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85 years and over |
16
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Recruitment
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Recruitment details |
dWe screened the operation schedule a day before surgery for eligibility. Patients had to be at least 45 years of age and underwent non-cardiac surgery. After meeting all inclusion criteria the patients was enrolled into the study. | |||||||||
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Pre-assignment
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Screening details |
- | |||||||||
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Pre-assignment period milestones
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Number of subjects started |
258 [1] | |||||||||
Number of subjects completed |
258 | |||||||||
| Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Surgery was postponed indefinitely. |
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Period 1
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Period 1 title |
Baseline Period (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind [2] | |||||||||
Roles blinded |
Subject, Assessor | |||||||||
Blinding implementation details |
Patients were not aware of the assigned oxygen concentration. Postoperative outcome assessor were no aware of the intraoperative administered oxygen concentration.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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80% Oxygen Group | |||||||||
Arm description |
Patients randomly assigned to the 80% oxygen group received 80% inspired oxygen concentration throughout surgery and for the first two postoperative hours. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
80% Oxygen
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Medicinal gas, liquefied
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Routes of administration |
Inhalation use
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Dosage and administration details |
80%Vol per hour study period % (V/V) percent volume/volume
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Investigational medicinal product name |
30% Oxygen
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Investigational medicinal product code |
30% Oxygen
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Other name |
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Pharmaceutical forms |
Medicinal gas, liquefied
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Routes of administration |
Inhalation use
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Dosage and administration details |
30%Vol per hour study period % (V/V) percent volume/volume
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Arm title
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30% Oxygen | |||||||||
Arm description |
Patients randomly assigned to the 30% oxygen group received 30% inspired oxygen concentration throughout surgery and for the first two postoperative hours. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
30% Oxygen
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Medicinal gas, liquefied
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Routes of administration |
Inhalation use
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Dosage and administration details |
30%Vol per hour study period % (V/V) percent volume/volume
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| Notes [2] - The roles blinded appear to be inconsistent with a double blind trial. Justification: Patients and outcome assessor were blinded. Blinding of the attending physician was not possible. |
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| Notes [3] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Surgery was postponed after randomisation indefinitely. 2 patients in the 80% oxygen were enrolled but surgery was not performed. |
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Baseline characteristics reporting groups
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Reporting group title |
80% Oxygen Group
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Reporting group description |
Patients randomly assigned to the 80% oxygen group received 80% inspired oxygen concentration throughout surgery and for the first two postoperative hours. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
30% Oxygen
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Reporting group description |
Patients randomly assigned to the 30% oxygen group received 30% inspired oxygen concentration throughout surgery and for the first two postoperative hours. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
80% Oxygen Group
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Reporting group description |
Patients randomly assigned to the 80% oxygen group received 80% inspired oxygen concentration throughout surgery and for the first two postoperative hours. | ||
Reporting group title |
30% Oxygen
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Reporting group description |
Patients randomly assigned to the 30% oxygen group received 30% inspired oxygen concentration throughout surgery and for the first two postoperative hours. | ||
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End point title |
NT-proBNP Concentration | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Postoperative NT-proBNP concentration was measured within 2hours after surgery and on the first and third postoperative day.
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Attachments |
Untitled (Filename: Oxygen SAE.xlsx) |
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Statistical analysis title |
Primary Outcome | ||||||||||||
Comparison groups |
80% Oxygen Group v 30% Oxygen
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Number of subjects included in analysis |
258
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Parameter type |
Median difference (final values) | ||||||||||||
Point estimate |
159
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-123 | ||||||||||||
upper limit |
431 | ||||||||||||
Statistical analysis title |
Secondary Outcome (MINS) | ||||||||||||
Comparison groups |
80% Oxygen Group v 30% Oxygen
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Number of subjects included in analysis |
258
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
0.887
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.475 | ||||||||||||
upper limit |
1.646 | ||||||||||||
| Notes [1] - For our secondary outcome we first performed a univariable logistic regression model (using firths correction) to analyze the influence of supplemental oxygen on the incidence of MINS. MINS was defined using the following perioperative high-sensitive Troponin T thresholds: a) troponin T of 20 to<65ng/L with an absolute change of at least 5 ng/Lor b) Troponin T level > 65ng/L. Furthermore, in patients whose Troponin T concentration was adjudicated from nonischemic etiology were not considered. |
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End point title |
Myocardial Injury after non cardiac surgery (MINS) | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Incidence of MINS within the first three days after surgery.
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Statistical analysis title |
Myocardial Injury after non cardiac Surgery | |||||||||
Comparison groups |
30% Oxygen v 80% Oxygen Group
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Number of subjects included in analysis |
258
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | |||||||||
P-value |
< 0.05 | |||||||||
Method |
Regression, Linear | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.887
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.475 | |||||||||
upper limit |
1.646 | |||||||||
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End point title |
Exploratory Outcomes | |||||||||
End point description |
Exploratory outcomes during hospitalisation include: Cardiac failure, Myocardial infarction, new-onset of cardiac arrhythmias, unplanned ICU admission, reoperation, respiratory failure, and bleeding.
Exploratory outcomes within 30-day after surgery include: cardiac failure, myocardial infarction, new-onset of cardiac arrhythmias, and death at day 30
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End point type |
Other pre-specified
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End point timeframe |
Exploratory outcomes include complications during hospitalisation and within 30 days after surgery.
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Statistical analysis title |
Exploratory Outcomes | |||||||||
Comparison groups |
80% Oxygen Group v 30% Oxygen
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Number of subjects included in analysis |
258
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | |||||||||
P-value |
< 0.05 | |||||||||
Method |
Fisher exact | |||||||||
Confidence interval |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Adverse events has been evaluated during hospitalisation and within 30 days after surgery via phone follow-up.
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Assessment type |
Systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
23.1
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| Frequency threshold for reporting non-serious adverse events: 5% | |||
| 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: File with SAE was attached. |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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29 Aug 2018 |
We changed our secondary outcome from postoperative plasma catecholamine concentrations (including noradrenaline, adrenaline and dopamine) to postoperative copeptin concentration measurement. |
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/34087659 http://www.ncbi.nlm.nih.gov/pubmed/34856530 |
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