ST Elevation Myocardial InfarctionPhase 2NCT03145194
TIMES: Ticagrelor vs. Placebo/ Clopidogrel With Aspirin in Anterior STEMI Patients Treated With Primary PCI
A Phase 2 study testing Ticagrelor in people with ST Elevation Myocardial Infarction, run by Papworth Hospital NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
This is a single-centred, double blind randomized controlled trial comparing ticagrelor with placebo in clopidogrel and aspirin loaded patients. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- ST Elevation Myocardial Infarction
- What is being tested?
- Ticagrelor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 30 Jan 2017to 30 Nov 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of informed verbal consent prior to any study specific procedures taking place with written consent confirmed prior to in-patient cardiac MRI.
- Male or female adult patient aged 18 - 90 years old
- Anterior STEMI (ST elevation ≥ 2mmHg in contiguous chest leads) with chest pain symptom onset < 12 hours
Who cannot join
- Cardiogenic shock*
- Previous anterior myocardial infarction
- Unfavourable coronary anatomy for PCI: left main / surgical or distal coronary disease
- Already prescribed Ticagrelor at the time of admission
- Factors affecting study drug administration/ absorption: vomiting or allergy
- Concomitant use of potent CYP3A4 inhibitors/ inducers (e.g ketoconazole and rifampicin) or CYP3A4 substrates with a narrow therapeutic window (e.g. cisapride and ergot alkaloids) or simvastatin / lovostatin >40mg oral dose.
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- Severe bleeding diathesis or current active bleeding*
- History of intracranial haemorrhage
- Moderate or Severe hepatic impairment
- Severe asthma or bradycardia/ complete heart block (contraindications to adenosine)*
- Severe co-morbidity with a life expectancy < 3 months.
- Women of child bearing potential (as determined by direct questioning of the patient to confirm and this will be documented in the medical notes).
- Patients that are found to have any excluding factor (e.g., unfavourable coronary anatomy for PCI) or develop any excluding factor (e.g., vomiting or cardiogenic shock) before the point of final IMR assessment will be discontinued from the study and followed up at discharge and by telephone at 3 and 12 months for adverse event monitoring purposes only.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Papworth Hospital NHS Foundation Trust
Papworth Everard, Cambridge, CB23 3RE
Stephen Hoole, 01480 366172 ext. 6172, s.hoole@nhs.net
Stephen Hoole
About this study
Official title: A Randomised Mechanistic Study Comparing the Effects of Different Anti-platelet Combinations (Ticagrelor vs. Placebo/ Clopidogrel) With Aspirin in Patients Presenting With Anterior STEMI Treated With Primary PCI
This is a single-centred, double blind randomized controlled trial comparing ticagrelor with placebo in clopidogrel and aspirin loaded patients.
Read the detailed description
The very early benefit of ticagrelor in STEMI is co-mediated by adenosine cardioprotection maintaining/ improving myocardial microcirculatory function, as well as via platelet inhibition or possibly other pleiotropic effects.
Ticagrelor increases circulating adenosine by reducing cellular re-uptake. Adenosine is a cardioprotective agent that utilizes cellular survival kinase pathways that may have beneficial effects on the microcirculation and myocardium in patients presenting with STEMI. Adenosine is currently used as a treatment for no-reflow and improves MVO post-STEMI when administered during PPCI. A recent study of healthy volunteers has confirmed that non-invasive coronary flow is augmented by ticagrelor and that this is mediated by adenosine. The Investigators propose that the very early beneficial effects of Ticagrelor in ACS may be adenosine mediated cardioprotection, rather than only due to an antiplatelet effect. This important research is original and a natural progression of the ticagrelor story. It expands the adenosine hypothesis and mode of action of ticagrelor and addresses a novel cardioprotective/ microcirculatory mechanism of action.
- Conditions
- ST Elevation Myocardial Infarction
- Being tested
- Ticagrelor, Placebo
- Medical subject headings
- ST Elevation Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TicagrelorDrug
2 x 90mg Ticagrelor tablets
PlaceboOther
2 x matching placebo tablets
| Study group | Role | What they receive |
|---|---|---|
| Ticagrelor | Experimental | Patients will receive Ticagrelor 180mg (2 x 90mg tablets) Receives: Drug: Ticagrelor |
| Placebo | Placebo comparator | Patients will receive Placebo (2 matching tablets) Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Index of Myocardial Resistance (IMR)
To compare final Index of Myocardial Resistance (IMR) at the end of the PPCI procedure between the two arms.
Measured: Baseline to end of PPCI procedure.
Secondary outcomes (7)
Baseline IMR and change in IMR during PPCI
To compare between the two arms.
Measured: Baseline to end of PPCI procedure.
ACF and AMR pre/post PPCI
To compare between the two arms.
Measured: Baseline to end of PPCI procedure.
TIMI flow and TMBG pre/post PPCI
To compare between the two arms.
Measured: Baseline to end of PPCI procedure.
ST segment resolution
To compare between the two arms.
Measured: Baseline to end of PPCI procedure.
OCT quantified clot volume pre/post PPCI
To compare between the two arms.
Measured: Baseline to end of PPCI procedure.
Cardiac troponin - I and CKMB levels at 0, 12 and 24 hours
To compare between the two arms.
Measured: Baseline to 24 hours.
Cardiac MRI microvascular obstruction between 24-48 hours and infarct size at 3 months
To compare between the two arms.
Measured: Baseline to 3 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2017
- Study start30 Jan 2017
- Primary completion30 Nov 2018 (estimated)
- Study completion30 Nov 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ST Elevation Myocardial InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Papworth Hospital NHS Foundation Trust
- Sponsor type
- Other government
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Stephen Hoole, Principal investigator, Papworth Hospital NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03145194
- Sponsor's protocol ID
- P01910
- Status last verified
- May 2017
- First submitted
- 13 Apr 2017
- Last updated
- 30 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Aetesam-Ur-Rahman M, Brown AJ, Jaworski C, Giblett JP, Zhao TX, Braganza DM, Clarke SC, Agrawal BSK, Bennett MR, West NEJ, Hoole SP. Adenosine-Induced Coronary Steal Is Observed in Patients Presenting With ST-Segment-Elevation Myocardial Infarction. J Am Heart Assoc. 2021 Jul 6;10(13):e019899. doi: 10.1161/JAHA.120.019899. Epub 2021 Jun 30.
PubMed 34187187
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Mechanistic Study Comparing the Effects of Different Anti-platelet Combinations (Ticagrelor vs. Placebo/ Clopidogrel) With Aspirin in Patients Presenting With Anterior STEMI Treated With Primary PCI
- ClinicalTrials.gov ID
- NCT03145194
- Acronym / sponsor ID
- P01910
- Conditions
- ST Elevation Myocardial Infarction
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Papworth Hospital NHS Foundation TrustOther government
- Collaborators
- AstraZeneca
- Study start
- 30 Jan 2017 (actual)
- Primary completion
- 30 Nov 2018 (estimated)
- Study completion
- 30 Nov 2019 (estimated)
- First posted
- 9 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-centred, double blind randomized controlled trial comparing ticagrelor with placebo in clopidogrel and aspirin loaded patients.
Detailed description
The very early benefit of ticagrelor in STEMI is co-mediated by adenosine cardioprotection maintaining/ improving myocardial microcirculatory function, as well as via platelet inhibition or possibly other pleiotropic effects.
Ticagrelor increases circulating adenosine by reducing cellular re-uptake. Adenosine is a cardioprotective agent that utilizes cellular survival kinase pathways that may have beneficial effects on the microcirculation and myocardium in patients presenting with STEMI. Adenosine is currently used as a treatment for no-reflow and improves MVO post-STEMI when administered during PPCI. A recent study of healthy volunteers has confirmed that non-invasive coronary flow is augmented by ticagrelor and that this is mediated by adenosine. The Investigators propose that the very early beneficial effects of Ticagrelor in ACS may be adenosine mediated cardioprotection, rather than only due to an antiplatelet effect. This important research is original and a natural progression of the ticagrelor story. It expands the adenosine hypothesis and mode of action of ticagrelor and addresses a novel cardioprotective/ microcirculatory mechanism of action.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ticagrelor | Experimental | Drug: TicagrelorPatients will receive Ticagrelor 180mg (2 x 90mg tablets) |
| Placebo | Placebo comparator | Other: PlaceboPatients will receive Placebo (2 matching tablets) |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Provision of informed verbal consent prior to any study specific procedures taking place with written consent confirmed prior to in-patient cardiac MRI.
- Male or female adult patient aged 18 - 90 years old
- Anterior STEMI (ST elevation ≥ 2mmHg in contiguous chest leads) with chest pain symptom onset < 12 hours
Key exclusion criteria (13 listed)
- Cardiogenic shock*
- Previous anterior myocardial infarction
- Unfavourable coronary anatomy for PCI: left main / surgical or distal coronary disease
- Already prescribed Ticagrelor at the time of admission
- Factors affecting study drug administration/ absorption: vomiting or allergy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ticagrelor2 x 90mg Ticagrelor tablets | Drug | Ticagrelor |
| Placebo2 x matching placebo tablets | Other | Placebo |
Primary outcome
Index of Myocardial Resistance (IMR)
Time frame: Baseline to end of PPCI procedure.
To compare final Index of Myocardial Resistance (IMR) at the end of the PPCI procedure between the two arms.
7 secondary outcomes
Baseline IMR and change in IMR during PPCI
Time frame: Baseline to end of PPCI procedure.
ACF and AMR pre/post PPCI
Time frame: Baseline to end of PPCI procedure.
TIMI flow and TMBG pre/post PPCI
Time frame: Baseline to end of PPCI procedure.
ST segment resolution
Time frame: Baseline to end of PPCI procedure.
OCT quantified clot volume pre/post PPCI
Time frame: Baseline to end of PPCI procedure.
Cardiac troponin - I and CKMB levels at 0, 12 and 24 hours
Time frame: Baseline to 24 hours.
Cardiac MRI microvascular obstruction between 24-48 hours and infarct size at 3 months
Time frame: Baseline to 3 months.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2017.
- Derived from this study: PubMed 34187187Aetesam-Ur-Rahman M, Brown AJ, Jaworski C, Giblett JP, Zhao TX, Braganza DM, Clarke SC, Agrawal BSK, Bennett MR, West NEJ, Hoole SP. Adenosine-Induced Coronary Steal Is Observed in Patients Presenting With ST-Segment-Elevation Myocardial Infarction. J Am Heart Assoc. 2021 Jul 6;10(13):e019899. doi: 10.1161/JAHA.120.019899. Epub 2021 Jun 30.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen Hoole principal investigator
Papworth Hospital NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ticagrelor in people with ST Elevation Myocardial Infarction, run by Papworth Hospital NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Stephen Hoole (01480 366172 ext. 6172, s.hoole@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Index of Myocardial Resistance (IMR) (time frame: Baseline to end of PPCI procedure.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03145194, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2017.