Diabetes MellitusPhase 3AUGEASNCT04069234
Study in Diabetes Mellitus Patients Without Prior Myocardial Infarction or Stroke Undergoing Elective Percutaneous Coronary Intervention.
A Phase 3 study testing Ticagrelor and Clopidogrel in people with Diabetes Mellitus and Microvascular Coronary Artery Disease, run by Region Skane.
Trial summary
This study is designed to test the hypothesis that ticagrelor is superior to clopidogrel, in improving coronary microvascular function, as measured by coronary flow reserve (CFR) in patients with T2DM at high risk of cardiovascular (CV) events undergoing elective PCI. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes Mellitus, Microvascular Coronary Artery Disease
- What is being tested?
- Ticagrelor and Clopidogrel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 15 Sep 2019to 31 Mar 2022
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of informed consent prior to any study specific procedures
- Men or women ≥18 years of age
- Diagnosed with T2DM defined as treatment with ongoing glucose lowering drug (oral medications and/or insulin) for at least 1 month
- Presence of CAD undergoing elective PCI
- Impaired coronary microvascular function post PCI as defined by a CFR ≤2.5 (as per local reading)
- TIMI 3 flow post PCI
Who cannot join
- Previous MI defined as a documented hospitalization with a final diagnosis of spontaneous MI (with the exception of definite secondary MI [e.g., due to coronary revascularization procedure, profound hypotension, hypertensive emergency, tachycardia, or profound anemia]).
- Previous stroke (transient ischemic attack [TIA] is not included in the stroke definition)
- Use of an intravenous antiplatelet therapy (i.e., cangrelor or GPI) during PCI
- On treatment with clopidogrel, prasugrel, or ticagrelor due to a prior acute major CV event (MI or stroke) (on treatment with clopidogrel due to prior vascular intervention not secondary to a major CV event is allowed)
- Planned use of aspirin treatment at doses >150 mg od
- Anticipated concomitant oral or intravenous therapy with strong cytochrome P450 3A4 (CYP3A4) inhibitors or CYP3A4 substrates with narrow therapeutic indices that cannot be stopped for the course of the study:
Show all 32Show fewer
- Strong CYP3A4 inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin (but not erythromycin or azithromycin), nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir
- CYP3A4 substrates with narrow therapeutic index: quinidine, simvastatin at doses >40 mg daily or lovastatin at doses >40 mg daily
- Hypersensitivity to ticagrelor or any of its excipients
- Need for chronic oral anticoagulant therapy or chronic low-molecular-weight heparin
- Patients with known bleeding diathesis or coagulation disorder
- History of intracerebral bleed at any time, gastrointestinal (GI) bleed within the past 6 months prior to randomization, or major surgery within 30 days prior to randomization
- Increased risk of bradycardic events (e.g., known sick sinus syndrome, second or third-degree AV block or previous documented syncope suspected to be due to bradycardia) unless treated with a pacemaker
- Known severe liver disease (e.g., ascites and/or clinical signs of coagulopathy)
- Renal failure requiring dialysis
- Known platelet count <145 x109 platelets/L
- Known hemoglobin <9 g/dL
- Women of child-bearing potential (WOCBP)*, who are not willing to use a method of contraception that is considered highly reliable** per CTFG (Clinical Trial Facilitation Group), OR who have a positive pregnancy test at enrolment or randomization OR women who are breast-feeding
- Inability of the patient to understand and/or comply with study procedures and/or follow up, in the opinion of the investigator, OR any conditions that, in the opinion of the investigator, may render the patient unable to complete the study
- Life expectancy of less than 6 month based on investigator's judgement
- Participation in another clinical study with an investigational (defined as non-approved) product, if taken within five half-lives or 28 days prior to the first administration of the trial medication, whichever is longer
- Previous randomization in the present study
- Severe asthma
- Hypersensitivity to adenosine or mannitol
- Long QT syndrome
- Chronic obstructive lung disease, with evidence of bronchospasm
- Severe low blood pressure
- Unstable angina pectoris
- Severe heart failure
- Hypovolemia
- Treatment with dipyradimol
- Increased intracranial pressure * fertile, following menarche until becoming post-menopausal, unless permanently sterile (permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy) ** estrogen/progestogen or progestogen (oral, intravaginal or transdermal administration); intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence
About this study
Official title: 30-d Rand, Eval-blind, Controlled, Multi-centre, Parallel, ph III Study to Evaluate Effect of a Low Maint Dose Ticagrelor Regimen vs Standard Dose Clopidogrel on Coronary Flow Reserve in DM Patients With Impaired Microvascular Function Without Prior MI or Stroke Undergoing ePCI.
This study is designed to test the hypothesis that ticagrelor is superior to clopidogrel, in improving coronary microvascular function, as measured by coronary flow reserve (CFR) in patients with T2DM at high risk of cardiovascular (CV) events undergoing elective PCI.
Read the detailed description
Coronary artery disease (CAD) can be divided into macrovascular and microvascular disease, both different manifestations of atherosclerosis. Macrovascular CAD, i.e. obstructive CAD of epicardial coronary arteries have traditionally been the focus of CAD treatment. Microvascular circulation, on the other hand, consists of arterioles (diameter <100 μm) within myocardium and abnormalities in this arterial bed may also impair myocardial perfusion and result in ischaemia. An indication of microvascular disease can be achieved with coronary flow reserve (CFR) which is an integrated measure of flow through both large epicardial arteries and coronary microcirculation. CFR measurement is the ratio of resting coronary artery mean diastolic flow velocity in comparison to hyperaemic coronary artery mean diastolic flow velocity, where hyperaemia is often induced with pharmacologic agent such as adenosine infusion. CFR of the left anterior descending (LAD) coronary artery during pharmacologic stress echocardiography has been found to provide effective prognostic information in patients with known or suspected CAD. This seems evident across patient populations, such as those with diabetes or chronic kidney disease, or older age. Particularly, a CFR <2.0 has been associated with markedly increased cardiovascular (CV) risk in an unselected patient population.
Ticagrelor primary mode of action is as a direct acting reversibly binding P2Y12 antagonist inhibiting ADP-induced platelet activation. However, ticagrelor has also been shown to increase extracellular adenosine concentration by inhibition of the equilibrative nucleoside transporter 1 (ENT1). Adenosine has been described to have a number of physiological effects including vasodilation, anti-inflammation, anti-platelet and cardioprotective effects and ticagrelor has been shown to enhance many of these adenosine-induced effects in animal models and in man. These adenosine-mediated effects may be beneficial to CAD patients and potentially impact coronary microvascular function and contribute to the clinical profile of ticagrelor. So far only one study has explored ticagrelor effect on coronary microvascular function. They showed, by using rubidium 82 positron emission tomography/computed tomography, that ticagrelor could improve local CFR compared to clopidogrel in CAD patients specifically in those regions that before treatment had impaired CFR (<2.5). CFR has been shown to be a strong independent predictor in diabetic patients with suspected coronary disease for future coronary events and survival.
The ongoing THEMIS study is designed to test the hypothesis that ticagrelor is superior to placebo, in prevention of major CV events, as measured by time to first event of the composite of CV death, MI, or stroke in patients with T2DM at high risk of CV events.
Patients undergoing elective PCI are excluded from the THEMIS study as these patients are treated with clopidogrel plus aspirin. The current study is designed to fill this data gap by generating clinically meaningful data with ticagrelor in THEMIS-like patients undergoing elective PCI.
- Being tested
- Ticagrelor, Clopidogrel
- Keywords
- myocardial infarction, percutaneous coronary invervention, coronary flow velocity reserve (CFR)
- Medical subject headings
- Diabetes Mellitus, Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TicagrelorDrug
ticagrelor 60 mg BID for 30 days
ClopidogrelDrug
clopidogrel 75mg OD for 30 Days
| Study group | Role | What they receive |
|---|---|---|
| Ticagrelor | Experimental | ticagrelor 60mg BID for 30 Days and ASA 75 - 150 mg once daily Receives: Drug: Ticagrelor |
| Clopidogrel | Active comparator | clopidogrel 75mg OD for 30 Days and ASA 75 - 150 mg once daily Receives: Drug: Clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Coronary Flow Velocity Reserve (CFR)
Difference in mean of individual absolute change from baseline to 30 days in Coronary Flow Velocity Reserve (CFR) in the mid-distal segment of the left anterior descending (LAD) coronary artery under adenosine infusion measured by Transthoracic Doppler Echocardiography (TDE) between the two arms
Measured: 30+/- 3 days after randomization
Secondary outcomes (2)
Coronary flow parameter-LAD hyperemic mean diastolic flow velocity
Difference in mean of individual absolute change from baseline at 30 days in:
- LAD hyperemic mean diastolic flow velocity
Measured: 30+/- 3 days after randomization
Coronary flow parameter-LAD resting mean diastolic flow velocity
Difference in mean of individual absolute change from baseline at 30 days
- LAD resting mean diastolic flow velocity
Measured: 30+/- 3 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2019
- Study start15 Sep 2019 (estimated)
- Primary completion15 Oct 2021 (estimated)
- Study completion31 Mar 2022 (estimated)
Why it stopped: Sponsor decided to stop the study due to commercial reasons.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Region SkaneThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Region Skane
- Sponsor type
- University, hospital or other
- Collaborators
- IHF GmbH - Institut für Herzinfarktforschung, Hippocrates Research, IRW consulting AB, AstraZeneca
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04069234
- Sponsor's protocol ID
- 2019-04160
- Other IDs
- 2019
- Acronym
- AUGEAS
- Status last verified
- Apr 2020
- First submitted
- 20 Aug 2019
- Last updated
- 8 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 30-d Rand, Eval-blind, Controlled, Multi-centre, Parallel, ph III Study to Evaluate Effect of a Low Maint Dose Ticagrelor Regimen vs Standard Dose Clopidogrel on Coronary Flow Reserve in DM Patients With Impaired Microvascular Function Without Prior MI or Stroke Undergoing ePCI.
- ClinicalTrials.gov ID
- NCT04069234
- Acronym / sponsor ID
- AUGEAS / 2019-04160
- Keywords
- myocardial infarction, percutaneous coronary invervention, coronary flow velocity reserve (CFR)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor decided to stop the study due to commercial reasons.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Region SkaneUniversity, hospital or other
- Collaborators
- IHF GmbH - Institut für Herzinfarktforschung, Hippocrates Research, IRW consulting AB, AstraZeneca
- Study start
- 15 Sep 2019 (estimated)
- Primary completion
- 15 Oct 2021 (estimated)
- Study completion
- 31 Mar 2022 (estimated)
- First posted
- 28 Aug 2019 (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 study is designed to test the hypothesis that ticagrelor is superior to clopidogrel, in improving coronary microvascular function, as measured by coronary flow reserve (CFR) in patients with T2DM at high risk of cardiovascular (CV) events undergoing elective PCI.
Detailed description
Coronary artery disease (CAD) can be divided into macrovascular and microvascular disease, both different manifestations of atherosclerosis. Macrovascular CAD, i.e. obstructive CAD of epicardial coronary arteries have traditionally been the focus of CAD treatment. Microvascular circulation, on the other hand, consists of arterioles (diameter <100 μm) within myocardium and abnormalities in this arterial bed may also impair myocardial perfusion and result in ischaemia. An indication of microvascular disease can be achieved with coronary flow reserve (CFR) which is an integrated measure of flow through both large epicardial arteries and coronary microcirculation. CFR measurement is the ratio of resting coronary artery mean diastolic flow velocity in comparison to hyperaemic coronary artery mean diastolic flow velocity, where hyperaemia is often induced with pharmacologic agent such as adenosine infusion. CFR of the left anterior descending (LAD) coronary artery during pharmacologic stress echocardiography has been found to provide effective prognostic information in patients with known or suspected CAD. This seems evident across patient populations, such as those with diabetes or chronic kidney disease, or older age. Particularly, a CFR <2.0 has been associated with markedly increased cardiovascular (CV) risk in an unselected patient population.
Ticagrelor primary mode of action is as a direct acting reversibly binding P2Y12 antagonist inhibiting ADP-induced platelet activation. However, ticagrelor has also been shown to increase extracellular adenosine concentration by inhibition of the equilibrative nucleoside transporter 1 (ENT1). Adenosine has been described to have a number of physiological effects including vasodilation, anti-inflammation, anti-platelet and cardioprotective effects and ticagrelor has been shown to enhance many of these adenosine-induced effects in animal models and in man. These adenosine-mediated effects may be beneficial to CAD patients and potentially impact coronary microvascular function and contribute to the clinical profile of ticagrelor. So far only one study has explored ticagrelor effect on coronary microvascular function. They showed, by using rubidium 82 positron emission tomography/computed tomography, that ticagrelor could improve local CFR compared to clopidogrel in CAD patients specifically in those regions that before treatment had impaired CFR (<2.5). CFR has been shown to be a strong independent predictor in diabetic patients with suspected coronary disease for future coronary events and survival.
The ongoing THEMIS study is designed to test the hypothesis that ticagrelor is superior to placebo, in prevention of major CV events, as measured by time to first event of the composite of CV death, MI, or stroke in patients with T2DM at high risk of CV events.
Patients undergoing elective PCI are excluded from the THEMIS study as these patients are treated with clopidogrel plus aspirin. The current study is designed to fill this data gap by generating clinically meaningful data with ticagrelor in THEMIS-like patients undergoing elective PCI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ticagrelor | Experimental | Drug: Ticagrelorticagrelor 60mg BID for 30 Days and ASA 75 - 150 mg once daily |
| Clopidogrel | Active comparator | Drug: Clopidogrelclopidogrel 75mg OD for 30 Days and ASA 75 - 150 mg once daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Provision of informed consent prior to any study specific procedures
- Men or women ≥18 years of age
- Diagnosed with T2DM defined as treatment with ongoing glucose lowering drug (oral medications and/or insulin) for at least 1 month
- Presence of CAD undergoing elective PCI
- Impaired coronary microvascular function post PCI as defined by a CFR ≤2.5 (as per local reading)
Key exclusion criteria (32 listed)
- Previous MI defined as a documented hospitalization with a final diagnosis of spontaneous MI (with the exception of definite secondary MI [e.g., due to coronary revascularization procedure, profound hypotension, hypertensive emergency, tachycardia, or profound anemia]).
- Previous stroke (transient ischemic attack [TIA] is not included in the stroke definition)
- Use of an intravenous antiplatelet therapy (i.e., cangrelor or GPI) during PCI
- On treatment with clopidogrel, prasugrel, or ticagrelor due to a prior acute major CV event (MI or stroke) (on treatment with clopidogrel due to prior vascular intervention not secondary to a major CV event is allowed)
- Planned use of aspirin treatment at doses >150 mg od
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 |
|---|---|---|
| Ticagrelorticagrelor 60 mg BID for 30 days | Drug | Ticagrelor |
| Clopidogrelclopidogrel 75mg OD for 30 Days | Drug | Clopidogrel |
Primary outcome
Coronary Flow Velocity Reserve (CFR)
Time frame: 30+/- 3 days after randomization
Difference in mean of individual absolute change from baseline to 30 days in Coronary Flow Velocity Reserve (CFR) in the mid-distal segment of the left anterior descending (LAD) coronary artery under adenosine infusion measured by Transthoracic Doppler Echocardiography (TDE) between the two arms
2 secondary outcomes
Coronary flow parameter-LAD hyperemic mean diastolic flow velocity
Time frame: 30+/- 3 days after randomization
Coronary flow parameter-LAD resting mean diastolic flow velocity
Time frame: 30+/- 3 days after randomization
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2020.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ticagrelor and Clopidogrel in people with Diabetes Mellitus and Microvascular Coronary Artery Disease, run by Region Skane.
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 6 inclusion and 32 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: withdrawn, as of the sponsor's last update on 8 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Coronary Flow Velocity Reserve (CFR) (time frame: 30+/- 3 days after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Apr 2020.