Clinical Trial Results:
Antiplatelet treatment in patients with diabetes mellitus: is there a difference between aspirin, clopidogrel and prasugrel
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Summary
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EudraCT number |
2009-011907-22 |
Trial protocol |
GB |
Global end of trial date |
31 Mar 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
09 May 2020
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First version publication date |
09 May 2020
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Other versions |
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Summary report(s) |
Antiplatelet in Diabetes final report |
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 |
ED09/8912
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University of Leeds
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Sponsor organisation address |
Worsley Building, Leeds, United Kingdom, LS2 9JT
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Public contact |
Dr Ramzi Ajjan, University of Leeds, R.Ajjan@leeds.ac.uk
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Scientific contact |
Dr Ramzi Ajjan, University of Leeds, R.Ajjan@leeds.ac.uk
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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 |
31 Mar 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Mar 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Mar 2014
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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 |
To compare the biochemical efficacy of Aspirin, Clopidegrel and Prasugrel in subjects with type 2 diabetes using a dual approach that investigates both platelet function and clot structure/fibrinolysis
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Protection of trial subjects |
This clinical trial, which involves the use of a medicinal product has been designed and will be run in accordance with the Principles of GCP and the current regulatory requirements, as detailed in the Medicines for Human Use (Clinical Trials) Regulations 2004 (UK S.I. 2004 / 1031) and any subsequent amendments of the clinical trial regulations.. The right of any individual to refuse consent without giving reasons will be respected. Furthermore, the patient will remain free to withdraw from the study at any time without giving reasons and without prejudicing any further treatment. Each participant will be involved in the study for a maximum of 10 weeks. Patients will need to attend on 5 occasions. Additional visits will be arranged at subject request or if this is deemed clinically necessary. AEs will be collected for all patients and will be evaluated for duration and intensity according to the NCRI Common Toxicity Criteria.
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Background therapy |
Diabetes is associated with increased risk of vascular disease, including heart attack and strokes 1. People with diabetes also have a worse short and long term prognosis following a heart attack with a higher death rate, when compared to non-diabetics 2. Antiplatelet therapy is an established management strategy for secondary prevention from cardiovascular events in people with diabetes, although the role of this agent in primary prevention in these subjects remains unclear as the evidence is both limited and inconclusive. Aspirin and clopidogrel are the two main antiplatelet agents currently in use, and they differ in their mechanism of action. Aspirin affects platelet function by inhibiting an enzyme called cyclo-oxygenase 1, which is important for the production of proteins involved in platelet activation. Furthermore, aspirin has a direct effect on the structure of blood clots, making them easier to breakdown (lyse) 3. Clopidogrel also inhibits the function of platelets but uses a different pathway by directly inhibiting platelet function through its action on a special receptor called P2Y12. In contrast to aspirin, the effects of this agent on clot structure and function are unknown. Prasugrel, a new antiplatelet agent that has recently obtained marketing authorization and that is now marketed in the UK, has a similar mode of action compared with clopidogrel but seems to have a superior clinical efficacy 4, which is probably related to greater and more consistent inhibition of platelet activation 5. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 May 2010
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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 |
United Kingdom: 56
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Worldwide total number of subjects |
56
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EEA total number of subjects |
56
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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) |
56
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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 |
Patients were eligible to participate if they were aged 18–75 years, already on treatment with aspirin 75 mg once-daily (OD) and able to give informed consent. | |||||||||
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Pre-assignment
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Screening details |
Patients will be recruited in the diabetes centre at Leeds Teaching Hospitals Trust and specialist cardiovascular/diabetes clinics. A verbal explanation of the trial and an Information Sheet will be provided by Dr Ajjan for the subject to consider. This will include detailed information about the rationale, design and personal implications | |||||||||
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Period 1
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Period 1 title |
Main Trial 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 | |||||||||
Roles blinded |
Subject, Investigator | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Aspirin 75mg, Clopidogrel 75mg, Prasugrel 10mg | |||||||||
Arm description |
All patients continued aspirin 75 mg OD for an initial lead-in period of 14 days. This arm then received clopidogrel 75 mg OD for 28 days then prasugrel 10 mg OD for 28 days. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Aspirin 75mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
All patients continued aspirin 75 mg OD for an
initial lead-in period of 14 days. One half then received
clopidogrel 75 mg OD for 28 days then prasugrel 10 mg
OD for 28 days, whilst the other half received prasugrel
10 mg OD for 28 days followed by clopidogrel 75 mg OD for 28 Days
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Investigational medicinal product name |
Clopidogrel 75mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
All patients continued aspirin 75 mg OD for an
initial lead-in period of 14 days. One half then received
clopidogrel 75 mg OD for 28 days then prasugrel 10 mg
OD for 28 days, whilst the other half received prasugrel
10 mg OD for 28 days followed by clopidogrel 75 mg OD for 28 Days
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Investigational medicinal product name |
Prasugrel 10mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
All patients continued aspirin 75 mg OD for an
initial lead-in period of 14 days. One half then received
clopidogrel 75 mg OD for 28 days then prasugrel 10 mg
OD for 28 days, whilst the other half received prasugrel
10 mg OD for 28 days followed by clopidogrel 75 mg OD for 28 Days
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Arm title
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Aspirin 75mg, Prasugrel 10mg, Clopidogrel 75mg | |||||||||
Arm description |
All patients continued aspirin 75 mg OD for an initial lead-in period of 14 days. This arm thenreceived prasugrel 10 mg OD for 28 days followed by clopidogrel 75 mg OD for 28 days, in an alternate sequence to Arm 1. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Aspirin 75mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
All patients continued aspirin 75 mg OD for an
initial lead-in period of 14 days. One half then received
clopidogrel 75 mg OD for 28 days then prasugrel 10 mg
OD for 28 days, whilst the other half received prasugrel
10 mg OD for 28 days followed by clopidogrel 75 mg OD for 28 Days
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Investigational medicinal product name |
Clopidogrel 75mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
All patients continued aspirin 75 mg OD for an
initial lead-in period of 14 days. One half then received
clopidogrel 75 mg OD for 28 days then prasugrel 10 mg
OD for 28 days, whilst the other half received prasugrel
10 mg OD for 28 days followed by clopidogrel 75 mg OD for 28 Days
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Investigational medicinal product name |
Prasugrel 10mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
All patients continued aspirin 75 mg OD for an
initial lead-in period of 14 days. One half then received
clopidogrel 75 mg OD for 28 days then prasugrel 10 mg
OD for 28 days, whilst the other half received prasugrel
10 mg OD for 28 days followed by clopidogrel 75 mg OD for 28 Days
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Baseline characteristics reporting groups
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Reporting group title |
Main Trial Period
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Reporting group description |
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End points reporting groups
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Reporting group title |
Aspirin 75mg, Clopidogrel 75mg, Prasugrel 10mg
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Reporting group description |
All patients continued aspirin 75 mg OD for an initial lead-in period of 14 days. This arm then received clopidogrel 75 mg OD for 28 days then prasugrel 10 mg OD for 28 days. | ||
Reporting group title |
Aspirin 75mg, Prasugrel 10mg, Clopidogrel 75mg
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Reporting group description |
All patients continued aspirin 75 mg OD for an initial lead-in period of 14 days. This arm thenreceived prasugrel 10 mg OD for 28 days followed by clopidogrel 75 mg OD for 28 days, in an alternate sequence to Arm 1. | ||
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End point title |
Prasugrel Maximum platelet aggregation response [1] | ||||||||||||
End point description |
Please note, maximum platelet aggregation response is recorded on the system for the each treatment. not via each arm in the study, as treatment was identical, just at different time points. This is to accommodate the unusual design of the study. For more information on the end point data, please see the attached publication.
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End point type |
Primary
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End point timeframe |
please see attached publication for the details regarding periods of assesment
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Please see attached publication for details of all statistical analysis |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Aspirin Maximum platelet aggregation response [2] | ||||||||||||
End point description |
Please note, maximum platelet aggregation response is recorded on the system for the each treatment. not via each arm in the study, as treatment was identical, just at different time points. This is to accommodate the unusual design of the study. For more information on the end point data, please see the attached publication.
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End point type |
Primary
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End point timeframe |
Please see attached publication for time frame details
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Please see attached publication for details of all statistical analysis |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Clopidogrel Maximum platelet aggregation response [3] | ||||||||||||
End point description |
Please note, maximum platelet aggregation response is recorded on the system for the each treatment, not via each arm in the study, as treatment was identical, just at different time points. This is to accommodate the unusual design of the study. For more information on the end point data, please see the attached publication.
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End point type |
Primary
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End point timeframe |
Please see attached publication for all timeframe details
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Please see attached publication for details of all statistical analysis |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
AEs will be collected for all patients at all visits, and will be evaluated for duration and intensity according to the NCRI Common Toxicity Criteria.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | |||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.0
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Reporting groups
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Reporting group title |
Aspirin 75mg, Clopidogrel 75mg, Prasugrel 10mg
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Reporting group description |
All patients continued aspirin 75 mg OD for an initial lead-in period of 14 days. This arm then received clopidogrel 75 mg OD for 28 days then prasugrel 10 mg OD for 28 days. | |||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Aspirin 75mg, Prasugrel 10mg, Clopidogrel 75mg
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Reporting group description |
All patients continued aspirin 75 mg OD for an initial lead-in period of 14 days. This arm thenreceived prasugrel 10 mg OD for 28 days followed by clopidogrel 75 mg OD for 28 days, in an alternate sequence to Arm 1. | |||||||||||||||||||||||||||||||||||||||||||||
| 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: Please see the attached final publication for details of Non-serious adverse events |
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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? Yes | |||
Date |
Amendment |
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19 Jun 2010 |
PIS amended to v4.0, to include the contact details of a new research nurse joining the research team |
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22 Jul 2011 |
Protocol & PIS amended to versions 4.0 & 5.0. |
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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 | |||
