Clinical Trial Results:
ASsessment of Platelet function and Inhibition in patients Recovering from a severe INfection
|
Summary
|
|
EudraCT number |
2016-004303-32 |
Trial protocol |
NL |
Global end of trial date |
10 Feb 2021
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
30 Dec 2023
|
First version publication date |
30 Dec 2023
|
Other versions |
|
Summary report(s) |
Statement |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
ASPIRIN-17
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Amsterdam Umc, location VUmc
|
||
Sponsor organisation address |
De Boelelaan 1117, Amsterdam, Netherlands, De Boelelaan 1117
|
||
Public contact |
Jeske van Diemen, Amsterdam Umc, location VUmc, 0031 630179557, jj.vandiemen@amsterdamumc.nl
|
||
Scientific contact |
Jeske van Diemen, Amsterdam Umc, location VUmc, 0031 630179557, jj.vandiemen@amsterdamumc.nl
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
12 Jan 2023
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
10 Feb 2021
|
||
Was the trial ended prematurely? |
Yes
|
||
|
General information about the trial
|
|||
Main objective of the trial |
Measuring the efficacy of aspirin in inhibiting platelet activity in patients during (recovery from) a severe infection.
|
||
Protection of trial subjects |
The protocol was approved by the medical ethical committee of the VU University Medical Center Amsterdam. Written informed consent was obtained from all participants.
|
||
Background therapy |
Observational epidemiological studies have confirmed what experienced clinicians suspected for many years: cardiovascular events can be triggered by a variety of common non-cardiovascular clinical conditions, particularly those that are associated with systemic inflammation. Acute systemic infection, like pneumonia, raises risk of myocardial infarction by approximately fivefold , and risk of stroke by eightfold . This increased risk is confined to the first 90 days after the onset of illness. This phenomenon of cardiovascular events occurring in patients hospitalized for non-cardiovascular conditions is clearly important, but the causal mechanisms are unclear and, thus, so are targeted preventive strategies. Nevertheless, there is evidence which suggests that, at least, one of the mechanism lies in the platelets’ response to the inflammation. Hence, targeting platelets with inhibitors could be used as a preventative strategy. | ||
Evidence for comparator |
Aspirin has been the number one prophylaxis for the prevention of cardiovascular events since the 1980's . We hypothesize that aspirin can prevent or attenuate (post-)inflammatory platelet hyperaggregability. | ||
Actual start date of recruitment |
01 Jan 2018
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Netherlands: 54
|
||
Worldwide total number of subjects |
54
|
||
EEA total number of subjects |
54
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
31
|
||
From 65 to 84 years |
22
|
||
85 years and over |
1
|
||
|
||||||||||
|
Recruitment
|
||||||||||
Recruitment details |
This is a multi-center open label randomized trial, performed in four hospitals in Amsterdam and Amstelveen, the Netherlands (Amsterdam UMC location VUmc, OLVG location East and West, hospital Amstelland). Patients from the Internal and Pulmonary medicine wards were screened for inclusion between April 2017 and December 2020. | |||||||||
|
Pre-assignment
|
||||||||||
Screening details |
All patients who were newly admitted to the internal and pulmonary medicine wards of the above-named hospitals were screened for inclusion according to the following inclusion criteria: a primary clinical diagnosis of pneumonia, or an invasive urinary tract infection or a soft tissue infection; age above 18 years, hospitalisation for at least 24 h | |||||||||
|
Pre-assignment period milestones
|
||||||||||
Number of subjects started |
61 [1] | |||||||||
Number of subjects completed |
54 | |||||||||
|
Pre-assignment subject non-completion reasons
|
||||||||||
Reason: Number of subjects |
Consent withdrawn by subject: 2 | |||||||||
Reason: Number of subjects |
Protocol deviation: 5 | |||||||||
| 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: The number of people that signed informed consent differs from the number of people in the baseline measurements, due to withdrawal of informed consent or not meeting the inclusion criteria in retrospect. We reported the number of people that were included in the baseline measurements as the worldwide number of people enrolled in the trial. |
||||||||||
|
Period 1
|
||||||||||
Period 1 title |
Study period (overall period)
|
|||||||||
Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
|
|||||||||
Blinding used |
Not blinded | |||||||||
|
Arms
|
||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||
|
Arm title
|
No intervention | |||||||||
Arm description |
- | |||||||||
Arm type |
No intervention | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
|
|||||||||
|
Arm title
|
Aspirin | |||||||||
Arm description |
Received aspirin 80mg | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
acetylsalicylic acid, non-enteric-coated
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||
Routes of administration |
Oral use
|
|||||||||
Dosage and administration details |
Oral, 80mg
|
|||||||||
|
||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
No intervention
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Aspirin
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Received aspirin 80mg | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
No intervention
|
||
Reporting group description |
- | ||
Reporting group title |
Aspirin
|
||
Reporting group description |
Received aspirin 80mg | ||
|
|||||||||||||
End point title |
the Platelet Function Analyzer Closure Time (PFA-CT) | ||||||||||||
End point description |
The Platelet Function Analyzer (PFA) measures platelet aggregation by simulating blood flow through an injured vessel. The closure time (CT) is the time needed for a blood plug to develop and occlude the hole in the cartridge. CT is inversely correlated with platelet aggregation; an increased or prolonged CT means decreased aggregation. A normal CT (< 193 seconds) despite aspirin use was determined aspirin resistant. TWe used the Collagen/Epinephrine Test Cartridge was used, which is sensitive to aspirin mediated effects. A CT greater than 300 seconds (the maximum) is reported as 301 for the data-analysis. In Amsterdam UMC location VUmc, the PFA-200® was used, the other hospitals used the PFA-100®.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
prior to randomization (T1), after intervention (T2) and after recovery (day 90) (T3)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Linear mixed models | ||||||||||||
Statistical analysis description |
Linear mixed models with measurements clustered within participants and with randomisation group as interaction term were performed to obtain changes with 95% confidence intervals between the different time points. Results were back-transformed for presentation and expressed as percentage.
|
||||||||||||
Comparison groups |
No intervention v Aspirin
|
||||||||||||
Number of subjects included in analysis |
54
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
|||||||||||||
|
|||||||||||
|
Adverse events information [1]
|
|||||||||||
Timeframe for reporting adverse events |
90 days
|
||||||||||
Assessment type |
Non-systematic | ||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||
Dictionary name |
MedDRA | ||||||||||
Dictionary version |
25
|
||||||||||
|
Reporting groups
|
|||||||||||
Reporting group title |
Bleeding
|
||||||||||
Reporting group description |
- | ||||||||||
|
|||||||||||
| 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: There were no non-serious adverse events in our study |
|||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
01 Jul 2019 |
Due to the COVID-19 pandemic and the exclusion of patients with suspected or confirmed Sars-Cov-2 infection, the inclusion rate radically decreased. We therefore halted the twice daily 40 mg group, and focused on the regular dosage regimen of once daily 80 mg. For analysis, we merged the two dosage groups together as the aspirin treatment group. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| An important limitation is the early termination of the study, resulting in a small sample size and the inability to compare the two dosage regimens. | |||
Online references |
|||
| http://www.ncbi.nlm.nih.gov/pubmed/37294478 |
|||
