Clinical Trial Results:
The effects of acetylsalicylic acid on immunoparalysis following human endotoxemia.
Summary
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EudraCT number |
2016-001971-61 |
Trial protocol |
NL |
Global end of trial date |
02 Nov 2016
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Results information
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Results version number |
v2(current) |
This version publication date |
23 Sep 2020
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First version publication date |
01 Feb 2020
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Other versions |
v1 |
Version creation reason |
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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 |
SALYCENDO
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02922673 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
CMO number: 2016-2550, ABR: 57410.091.16 | ||
Sponsors
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Sponsor organisation name |
Radboudumc
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Sponsor organisation address |
Geert Grooteplein 10, Nijmegen, Netherlands,
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Public contact |
Research IC, office of Guus Leijte, Radboudumc, +31 0243668420, guus.leijte@radboudumc.nl
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Scientific contact |
Research IC, office of Guus Leijte, Radboudumc, +31 0243668420, guus.leijte@radboudumc.nl
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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 |
08 Jan 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
02 Nov 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Nov 2016
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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 |
1. To determine whether acetylsalicylic acid treatment can reverse endotoxin tolerance, which is expressed as a decrease in pro-inflammatory cytokine levels between the first and second endotoxin challenge.
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Protection of trial subjects |
Subjects were carefully instructed during the trial.
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Background therapy |
All subjects underwent an endotoxin challenge twice, with an interval of one week in-between. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Sep 2016
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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 |
Netherlands: 30
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Worldwide total number of subjects |
30
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EEA total number of subjects |
30
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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) |
30
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Healthy male subjects will be recruited by posters at several faculties on the campus of the Radboud University Nijmegen and using the Radboud University website. | ||||||||||||
Pre-assignment
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Screening details |
All subjects gave written informed consent and medical history, physical examination, laboratory tests, and a 12-leads electrocardiogram did not reveal any abnormalities. | ||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | ||||||||||||
Blinding implementation details |
Subjects will be randomly allocated to prophylaxis, treatment or control group using a sealed envelope opened by a research nurse not involved in the study. The allocated study medication will be delivered in identical packs, as identical capsules, by an independent nurse. The randomization will only be broken only if necessary for safety reasons. The investigators and participating subjects will be blinded for treatment allocation until all study endpoint are known and the database is locked.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Control group | ||||||||||||
Arm description |
control group receiving placebo | ||||||||||||
Arm type |
Placebo | ||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
PL1
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Enteral use
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Dosage and administration details |
Oral use
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Arm title
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Treatment group | ||||||||||||
Arm description |
80 mg acetylsalicylic acid daily for the 7-d period in-between both endotoxin challenges | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Acetylsalicylic acid
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Investigational medicinal product code |
PR1
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Other name |
Aspirin
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Pharmaceutical forms |
Dispersible tablet
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Routes of administration |
Enteral use
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Dosage and administration details |
80 milligram per day, oral use
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
PL1
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Enteral use
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Dosage and administration details |
Oral use
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Arm title
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Prophylaxis group | ||||||||||||
Arm description |
80 mg acetylsalicylic acid daily for a 14-d period,starting 7 d before the first endotoxin challenge | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Acetylsalicylic acid
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Investigational medicinal product code |
PR1
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Other name |
Aspirin
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Pharmaceutical forms |
Dispersible tablet
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Routes of administration |
Enteral use
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Dosage and administration details |
80 milligram per day, oral use
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Baseline characteristics reporting groups
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Reporting group title |
Control group
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Reporting group description |
control group receiving placebo | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Treatment group
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Reporting group description |
80 mg acetylsalicylic acid daily for the 7-d period in-between both endotoxin challenges | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Prophylaxis group
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Reporting group description |
80 mg acetylsalicylic acid daily for a 14-d period,starting 7 d before the first endotoxin challenge | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Control group
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Reporting group description |
control group receiving placebo | ||
Reporting group title |
Treatment group
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Reporting group description |
80 mg acetylsalicylic acid daily for the 7-d period in-between both endotoxin challenges | ||
Reporting group title |
Prophylaxis group
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Reporting group description |
80 mg acetylsalicylic acid daily for a 14-d period,starting 7 d before the first endotoxin challenge |
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End point title |
Area under the TNFa concentration time curve | ||||||||||||||||
End point description |
Area under the TNFa concentration time curve
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End point type |
Primary
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End point timeframe |
TNF concentration is determined on challenge days from baseline (just before endotoxin administration) up to 8 hours post challenge.
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Statistical analysis title |
Two-way ANOVA for primary endpoint | ||||||||||||||||
Statistical analysis description |
Two-way ANOVA for cytokine concentration data over time.
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Comparison groups |
Treatment group v Control group v Prophylaxis group
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
The investigator will report all SAEs to the sponsor without undue delay after obtaining knowledge of the events.
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Adverse event reporting additional description |
The sponsor will report the SAEs through the web portal ToetsingOnline to the accredited METC that approved the protocol.
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Assessment type |
Non-systematic | ||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
ToetsingOnline | ||||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
Did not have any AE during this study
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Reporting group description |
Did not have any AE during this study | ||||||||||||||||
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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 |