Download PDF

Clinical Trial Results:
Does acetylsalicylic acid reduce the mortality of patients admitted to an Intensive Care Unit

Summary
EudraCT number	2012-002235-29
Trial protocol	AT
Global end of trial date	05 Sep 2017

Results information
Results version number	v2(current)
This version publication date	03 Sep 2019
First version publication date	02 Feb 2018
Other versions	v1
Version creation reason	Correction of full data set Correction for statistical testing: we did not test for equivalence, but for superiority

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

1.0

ISRCTN number

US NCT number

NCT02285153

WHO universal trial number (UTN)

Sponsor organisation name

Medical University of Vienna

Sponsor organisation address

Waehringer Guertel 18-20, Vienna, Austria, 1090

Public contact

Medizinische Universität Wien - Uni, Medizinische Universität Wien - Universitätsklinik für klinische Pharmakologie, 0043 01404002980, klin-pharmakologie@meduniwien.ac.at

Scientific contact

Medizinische Universität Wien - Uni, Medizinische Universität Wien - Universitätsklinik für klinische Pharmakologie, 0043 01404002980, klin-pharmakologie@meduniwien.ac.at

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

10 Nov 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

05 Sep 2017

Was the trial ended prematurely?

Yes

Main objective of the trial

To investigate the 28-/90-day mortality of patients treated with ASA vs. placebo;

Protection of trial subjects

Daily blood samples were drawn on a routine basis. Furthermore physical examinations were performed every day by trained physicians.

Background therapy

Participation in this trial did not affect background therapy of patients. Placebo or acetylsalicylic acid were add-on therapy to the usual treatment of the patients.

Evidence for comparator

This was a placebo controlled trial. We investigated whether acetylsalicylic acid reduced the mortality of critically ill patients compared to placebo. Since this was an add-on treatment the use of an active comparator was not indicated.

Actual start date of recruitment

15 Nov 2011

Long term follow-up planned

Yes

Long term follow-up rationale

Efficacy

Long term follow-up duration

3 Months

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Austria: 15

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

15 Patients participated in this trial. The first patient was included on November 15th 2012. The last patient on March 13th 2014. All were recruited in the General Hospital of Vienna, Austria.

Screening details

Patients admitted to an ICU without platelet inhibitors, with no recent or planned invasive procedures or surgeries, with no active bleeding, no coagulation disorders, no low platelet counts, no terminal illness (anticipated life expectancy < 3 months), at the discretion of the treating physician were eligible for inclusion.

Number of subjects started

Number of subjects completed

Period 1 title

Treatment period (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst

Blinding implementation details

Patients were randomized by a trained person not otherwise involved in the conduct of the trial. Treatment was prepared and the ICU ward received the study drug on each day. Verum/Placebo were not distinguishable by its physical appearance.

Are arms mutually exclusive

Yes

Placebo

Arm description

Placebo Arm

Arm type

Placebo

Investigational medicinal product name

Sodium chloride

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

100ml 0.9% sodium chloride solution

Verum

Arm description

100mg Acetylsalicylic Acid per day

Arm type

Experimental

Investigational medicinal product name

Acetylsalicylic acid

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for concentrate for solution for infusion

Routes of administration

Intracavernous use

Dosage and administration details

1 Infusion of 100mg Acetylsalicylic Acid in 100ml 0.9% sodium chloride solution

Number of subjects in period 1	Placebo	Verum
Started	8	7
Completed	8	6
Not completed	0	1
Adverse event, non-fatal	-	1

Baseline characteristics

Top of page

Reporting group title

Placebo

Reporting group description

Placebo Arm

Reporting group title

Verum

Reporting group description

100mg Acetylsalicylic Acid per day

Reporting group values	Placebo	Verum	Total
Number of subjects	8	7	15
Age categorical
Age at Inclusion
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	4	5	9
From 65-84 years	4	2	6
85 years and over	0	0	0
Age continuous
Age at inclusion
Units: years
median (standard deviation)	63 ± 10	61 ± 15	-
Gender categorical
Gender
Units: Subjects
Female	2	4	6
Male	6	3	9
SAPS III score
stratification variable
Units: Subjects
<50	1	1	2
>50	7	6	13
Age
stratification variable
Units: Subjects
>60	4	3	7
<60	4	4	8
SAPS III
Disease score
Units: points
arithmetic mean (standard deviation)	63 ± 13	64 ± 19	-

End points

Top of page

Reporting group title

Placebo

Reporting group description

Placebo Arm

Reporting group title

Verum

Reporting group description

100mg Acetylsalicylic Acid per day

Primary: day 28 mortality

Top of page

End point title

day 28 mortality

End point description

primary endpoint Due to the early termination of the trial due to recruitment problems no formal statistical analysis was performed.

End point type

Primary

End point timeframe

28 days after ICU inclusion

End point values	Placebo	Verum
Number of subjects analysed	8	7
Units: deaths
dead	1	1
alive	7	6

Mortality

Statistical analysis description

Day 28/90 Mortality

Comparison groups

Placebo v Verum

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

= 0.57 ^[2]

Method

Chi-squared

Parameter type

Cox proportional hazard

Point estimate

0.434

Confidence interval

level

95%

sides

2-sided

lower limit

0.039

upper limit

4.792

Variability estimate

Standard error of the mean

Dispersion value

1.225

Notes
[1] - Chi2
[2] - There is no significant difference in mortality between the two groups.

Primary: 90-day mortality

Top of page

End point title

90-day mortality

End point description

Deaths within 90 days of inclusion

End point type

Primary

End point timeframe

day 90 mortality

End point values	Placebo	Verum
Number of subjects analysed	8	7
Units: deaths
dead	1	2
alive	7	6

Mortality

Statistical analysis description

Day 90 mortality between two groups

Comparison groups

Placebo v Verum

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

= 0.57 ^[4]

Method

Chi-squared

Confidence interval

level

95%

Variability estimate

Standard error of the mean

Notes
[3] - Chi2
[4] - There is no difference between the two groups.

Secondary: Major bleeding

Top of page

End point title

Major bleeding

End point description

Major bleedings during the Treatment phase of the trial

End point type

Secondary

End point timeframe

Duration of the Treatment phase

End point values	Placebo	Verum
Number of subjects analysed	8	7
Units: Major bleedings
Major bleeding	0	1

Major bleeding

Statistical analysis description

major bleeding in both groups.

Comparison groups

Placebo v Verum

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

= 0.467 ^[6]

Method

Chi-squared

Confidence interval

Notes
[5] - Chi2 Test
[6] - There is no significant difference between the two groups with regards to bleeding incidences.

Secondary: Thromboembolic events

Top of page

End point title

Thromboembolic events

End point description

End point type

Secondary

End point timeframe

Duration of Treatment

End point values	Placebo	Verum
Number of subjects analysed	8	7
Units: Thromboembolic events
Thromboembolic events	1	0

Thromboembolic Events

Statistical analysis description

Thromboembolic Events during the treatment phase

Comparison groups

Placebo v Verum

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[7]

P-value

= 1 ^[8]

Method

Chi-squared

Confidence interval

Notes
[7] - Chi2 Test
[8] - There was no significant difference in the number of thromboembolic events between the two groups.

Adverse events

Top of page

Timeframe for reporting adverse events

The duration of the ICU Stay

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Verum

Reporting group description

Patients who received 100mg Acetylsalicylic acid

Reporting group title

Placebo

Reporting group description

Serious adverse events	Verum	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 7 (28.57%)	3 / 8 (37.50%)
number of deaths (all causes)	1	1
number of deaths resulting from adverse events	0	0
Cardiac disorders
Asystolia
alternative assessment type: Systematic
subjects affected / exposed	1 / 7 (14.29%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
hypoxic brain damage
subjects affected / exposed	0 / 7 (0.00%)	1 / 8 (12.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Colon Perforation
alternative assessment type: Systematic
subjects affected / exposed	1 / 7 (14.29%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Aspiration Pneumonia
subjects affected / exposed	0 / 7 (0.00%)	2 / 8 (25.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Acute renal failure
subjects affected / exposed	1 / 7 (14.29%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Catheter infection
subjects affected / exposed	0 / 7 (0.00%)	1 / 8 (12.50%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 1%

Non-serious adverse events	Verum	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	4 / 7 (57.14%)	6 / 8 (75.00%)
Vascular disorders
Bleeding
Additional description: minor bleeding according to the TIMI-bleeding criteria
subjects affected / exposed	1 / 7 (14.29%)	0 / 8 (0.00%)
occurrences all number	1	0
Cardiac disorders
atrial fibrillation
subjects affected / exposed	0 / 7 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	1
Nervous system disorders
Delirium
subjects affected / exposed	2 / 7 (28.57%)	1 / 8 (12.50%)
occurrences all number	2	1
General disorders and administration site conditions
Nausea
subjects affected / exposed	0 / 7 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	1
Gastrointestinal disorders
Obstipation
subjects affected / exposed	0 / 7 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	1
Respiratory, thoracic and mediastinal disorders
Pneumothorax
subjects affected / exposed	0 / 7 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	1
Pleural effusion
subjects affected / exposed	1 / 7 (14.29%)	0 / 8 (0.00%)
occurrences all number	1	0
Hepatobiliary disorders
Liver function test increased
subjects affected / exposed	1 / 7 (14.29%)	0 / 8 (0.00%)
occurrences all number	1	0
Infections and infestations
Pneumonia
subjects affected / exposed	1 / 7 (14.29%)	2 / 8 (25.00%)
occurrences all number	1	2
Catheter infection
subjects affected / exposed	1 / 7 (14.29%)	0 / 8 (0.00%)
occurrences all number	1	0
Wound infection
subjects affected / exposed	1 / 7 (14.29%)	0 / 8 (0.00%)
occurrences all number	1	0
herpes virus infection
subjects affected / exposed	1 / 7 (14.29%)	0 / 8 (0.00%)
occurrences all number	1	0

More information

Top of page

Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

The trial was terminated after 15 patients due to recruitment difficulties. Thus, any statistical analysis and interpretation of trial results should only be done with caution.

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Clinical trials

Clinical Trial Results:
Does acetylsalicylic acid reduce the mortality of patients admitted to an Intensive Care Unit

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: day 28 mortality

Primary: day 28 mortality

Primary: 90-day mortality

Primary: 90-day mortality

Secondary: Major bleeding

Secondary: Major bleeding

Secondary: Thromboembolic events

Secondary: Thromboembolic events

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: Does acetylsalicylic acid reduce the mortality of patients admitted to an Intensive Care Unit

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: day 28 mortality

Primary: day 28 mortality

Primary: 90-day mortality

Primary: 90-day mortality

Secondary: Major bleeding

Secondary: Major bleeding

Secondary: Thromboembolic events

Secondary: Thromboembolic events

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Does acetylsalicylic acid reduce the mortality of patients admitted to an Intensive Care Unit