Peripheral Artery Disease (PAD)Phase 2TI-PAD EVRNCT02227368
Walking Effect of Long Term Ticagrelor in Subjects With PAD Who Have Undergone EVR
A Phase 2 study testing Ticagrelor and Comparator in people with Peripheral Artery Disease (PAD), run by AstraZeneca at 10 sites in United States.
Trial summary
To compare the effect of ticagrelor versus aspirin on the change in peak walking time, evaluated on the graded treadmill test, from one to 26 weeks post-revascularization in patients with peripheral artery disease who have undergone endovascular revascularization for moderate to severe claudication or ischemic rest… Read more about this study
- Who is it for?
- Ages 50 to 130 years
- Conditions the study is for
- Peripheral Artery Disease (PAD)
- What is being tested?
- Ticagrelor and Comparator
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 10 sitesUnited States
- Study dates
- 20 Oct 2014to 23 May 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 50 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent prior to any study specific procedures.
- Ambulatory male or female outpatients aged 50 years of age or older at the time of the Screening Visit.
- EVR, below the inguinal ligament that includes the distal SFA and/or popliteal and/or tibial arteries, that is planned to occur within 5 weeks after the Screening Visit, as determined and clearly documented by the Principal Investigator or physician Sub-Investigator (MD/DO). Patients undergoing a proximal revascularization may be enrolled as long as their procedure also includes treating the distal SFA, popliteal or tibial arteries. The EVR must be confirmed as technically successful (a completed procedure where haemostasis has been achieved) before the patient is randomised.
- Normal inflow into the lower extremity as determined by the Principal Investigator or physician Sub-Investigator (MD/DO). Adequacy of inflow can be assessed by hemodynamic measures, angiography or other imaging modalities obtained during Screening or recorded in the medical records up to 30 days prior to the Screening Visit or as defined by imaging at the time of the procedure. A patient with inadequate inflow at the time of Screening can still be enrolled if the inflow is addressed and resolved by the planned revascularization procedure.
- Diagnosis of PAD confirmed by history and any one of the following observed in the index (intervention) leg at the Screening Visit:
- Resting ABI ≤0.90, or
- In patients with an ABI > 1.40 (non-compressible vessels) a resting GTI <0.70 can be used for inclusions.
- Patient has been advised of the beneficial effects of smoking cessation and exercise therapy but is not in the process of changing their smoking status or exercise at the time of the Screening Visit.
Who cannot join
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- Revascularisation planned only to treat proximal (inflow) disease in the iliac and/or common femoral arteries.
- Previous randomisation in the present study.
- Participation in another clinical study with an investigational product within the last 3 months or any new clinical trial during the course of this study.
- Gangrene or ischemic ulcer of either lower extremity.
- PAD of a non-atherosclerotic nature.
Show all 29Show fewer
- Clinical necessity to use dual antiplatelet therapy within 7 days prior to randomisation, or single anti-platelet therapy (ticlopidine, prasugrel, vorapaxar, ticagrelor or dipyridamole) other than clopidogrel or aspirin. Clopidogrel or aspirin can be taken up to and including the time that the loading dose is being given.
- Clinical necessity to use the following restricted concomitant medications within 4 weeks prior to randomisation. Patients taking any of these medications at the Screening Visit may be considered for randomisation after a 4 week washout period from the medication.
- Pentoxifylline or cilostazol for relief of claudication symptoms
- Chronic oral or parenteral anticoagulant therapy (greater than 7 days)
- Strong inhibitors of CYP3A enzymes (Section 5.6.9.1)
- Strong inducers of CYP3A enzymes (Section 5.6.9.2)
- Simvastatin or lovastatin at daily doses over 40 mg
- Any disease process (e.g. angina, cardiac abnormality, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), respiratory disease, obesity, stroke, severe neuropathy of the foot, symptomatic musculoskeletal disease of the lower extremity), other than PAD, that would interfere with exercise performance during the ETT or prevent the patient from reaching their claudication-limited PWT as the primary endpoint of the study.
- Coronary, aortic surgery, angioplasty, lumbar sympathectomy or lower extremity surgery that impacts the ability to walk on a treadmill within the past 3 months prior to EVR. Revascularization of the non-index lower extremity within the past 4 weeks prior to EVR.
- Any major lower limb amputation due to PAD anticipated within the next 3 months or prior major amputation due to PAD (minor toe amputations allowed if it does not interfere with ambulation).
- Myocardial infarction or stroke in the previous 3 months.
- Any concomitant disease process with a life expectancy of less than 1 year or which is sufficiently severe as to compromise the validity of test performance.
- Dementia likely to jeopardise understanding of information pertinent to study conduct or compliance to study procedures.
- Concern for the inability of the patient to comply with study procedures and/or followup (e.g., alcohol or drug abuse).
- Resting systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥95 mmHg at the Screening Visit, in spite of antihypertensive treatments allowed by the protocol.
- A known bleeding diathesis, haemostatic or coagulation disorder, or systemic bleeding, whether resolved or ongoing.
- Known severe liver disease (e.g., ascites and or clinical signs of coagulopathy).
- Renal failure requiring dialysis.
- History of previous intracranial bleed at any time, gastrointestinal bleed within the past 6 months, or major surgery within 30 days (if the surgical wound is judged to be associated with an increased risk of bleeding).
- History of thrombocytopenia or neutropenia.
- Hypersensitivity to ticagrelor, aspirin or lactose.
- Initiation of antidiabetic, antihypertensive, lipid-lowering and beta-blocking drugs within 1 month prior to the Screening Visit.
- Pregnancy, lactation, fertility without protection against pregnancy (for women of childbearing potential; a urine or serum pregnancy test will be performed at the Screening Visit).
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Research Site
Cleveland, Ohio, 44195
Research Site
Daytona Beach, Florida, 32114
Research Site
Jacksonville, Florida, 32216
Research Site
McKinney, Texas, 75069
Research Site
Munster, Indiana, 46321
Research Site
New York, New York, 10001
Research Site
Ocala, Florida, 34471
Research Site
San Antonio, Texas, 78229
Research Site
Sarasota, Florida, 34239
Research Site
Yonkers, New York, 10701
About this study
Official title: A Phase II Multicentre, Randomised, Double-Blind, Controlled, Parallel-Group Study to Evaluate the Walking Time Effect of Long-Term Ticagrelor in Comparison to Long-Term Aspirin Administration in Ambulatory Patients With Peripheral Artery Disease Undergoing Endovascular Revascularization - The Ticagrelor in Peripheral Artery Disease Endovascular Revascularization Study TI-PAD I EVR
To compare the effect of ticagrelor versus aspirin on the change in peak walking time, evaluated on the graded treadmill test, from one to 26 weeks post-revascularization in patients with peripheral artery disease who have undergone endovascular revascularization for moderate to severe claudication or ischemic rest pain.
Read the detailed description
A Phase II Multicentre, Randomised, Double-Blind, Controlled, Parallel-Group Study to Evaluate the Walking Time Effect of Long-Term Ticagrelor in Comparison to Long-Term Aspirin Administration in Ambulatory Patients with Peripheral Artery Disease Undergoing Endovascular Revascularization - The Ticagrelor in Peripheral Artery Disease Endovascular Revascularization Study TI-PAD I EVR.
- Conditions
- Peripheral Artery Disease (PAD)
- Being tested
- Ticagrelor, Comparator
- Keywords
- Myocardial Infarction, Peripheral Arterial disease, Mycardial Ischemia, Heart Diseases, Cardiovascular Diseases, Vascular Diseases, Altherosclerosis, Arteriosclerosis, Arterial Occlusive Diseases, Peripheral Vascular Diseases, Ticagrelor, Ticlopidine, Platelet Aggregation inhibitors, Hematologic Agents, Therapeutic Uses, Pharmacologic Actions, Purinegic P2Y Receptor Antagonists, Purinegic P2 Receptor Antagonists, Purinergic Antagonists, Purinergic Agents
- Medical subject headings
- Peripheral Arterial Disease, Myocardial Infarction, Heart Diseases, Cardiovascular Diseases, Vascular Diseases, Arteriosclerosis, Arterial Occlusive Diseases, Peripheral Vascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TicagrelorDrug
Also called Brilinta
Antiplatelet therapy approved for ACS. Antagonist of P2Y12 and inhibitor of adenosine diphosphate (ADP)-induced platelet aggregation.
ComparatorDrug
Also called Aspirin
Aspirin monotherapy anti-platelet treatment for PAD patients following EVR procedures
| Study group | Role | What they receive |
|---|---|---|
| Ticagrelor | Experimental | 26 Weeks of ticagrelor 90mg twice a day plus aspirin placebo once daily Receives: Drug: Ticagrelor |
| Aspirin | Active comparator | 26 Weeks of aspirin 100mg once daily plus ticagrelor placebo twice a day Receives: Drug: Comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Log Transformed Peak Walking Time (PWT) at Week 26 or Early Termination (ET)
Measured: 26 Weeks
Secondary outcomes (1)
Change From Baseline in Log Transformed Claudication Onset Time (COT) at Week 26 or Early Termination (ET)
Measured: 26 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2014 (estimated)
- Study start20 Oct 2014
- Primary completion23 May 2016
- Study completion23 May 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Peripheral Artery Disease (PAD)Studies of the same condition, open and under way.
- More trials run by AstraZenecaThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- CPC Clinical Research
- Responsible party
- Sponsor
- Investigators
- William Hiatt, MD, Principal investigator, Colorado Prevention Center Clinical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02227368
- Sponsor's protocol ID
- D5135L00003
- Acronym
- TI-PAD EVR
- Status last verified
- Jun 2017
- First submitted
- 19 Aug 2014
- Last updated
- 19 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Rogers RK, Hiatt WR, Patel MR, Shishehbor MH, White R, Khan ND, Bhalla NP, Jones WS, Low Wang CC. Ticagrelor in Peripheral Artery Disease Endovascular Revascularization (TI-PAD): Challenges in clinical trial execution. Vasc Med. 2018 Dec;23(6):513-522. doi: 10.1177/1358863X18760996. Epub 2018 Apr 9.
PubMed 29629845
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Multicentre, Randomised, Double-Blind, Controlled, Parallel-Group Study to Evaluate the Walking Time Effect of Long-Term Ticagrelor in Comparison to Long-Term Aspirin Administration in Ambulatory Patients With Peripheral Artery Disease Undergoing Endovascular Revascularization - The Ticagrelor in Peripheral Artery Disease Endovascular Revascularization Study TI-PAD I EVR
- ClinicalTrials.gov ID
- NCT02227368
- Acronym / sponsor ID
- TI-PAD EVR / D5135L00003
- Conditions
- Peripheral Artery Disease (PAD)
- Keywords
- Myocardial Infarction, Peripheral Arterial disease, Mycardial Ischemia, Heart Diseases, Cardiovascular Diseases, Vascular Diseases, Altherosclerosis, Arteriosclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 40 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- CPC Clinical Research
- Study start
- 20 Oct 2014 (actual)
- Primary completion
- 23 May 2016 (actual)
- Study completion
- 23 May 2016 (actual)
- First posted
- 28 Aug 2014 (estimated)
- Results
- Posted 14 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To compare the effect of ticagrelor versus aspirin on the change in peak walking time, evaluated on the graded treadmill test, from one to 26 weeks post-revascularization in patients with peripheral artery disease who have undergone endovascular revascularization for moderate to severe claudication or ischemic rest pain.
Detailed description
A Phase II Multicentre, Randomised, Double-Blind, Controlled, Parallel-Group Study to Evaluate the Walking Time Effect of Long-Term Ticagrelor in Comparison to Long-Term Aspirin Administration in Ambulatory Patients with Peripheral Artery Disease Undergoing Endovascular Revascularization - The Ticagrelor in Peripheral Artery Disease Endovascular Revascularization Study TI-PAD I EVR.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ticagrelor | Experimental | Drug: Ticagrelor26 Weeks of ticagrelor 90mg twice a day plus aspirin placebo once daily |
| Aspirin | Active comparator | Drug: Comparator26 Weeks of aspirin 100mg once daily plus ticagrelor placebo twice a day |
Who may qualify
- Ages
- 50 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Written informed consent prior to any study specific procedures.
- Ambulatory male or female outpatients aged 50 years of age or older at the time of the Screening Visit.
- EVR, below the inguinal ligament that includes the distal SFA and/or popliteal and/or tibial arteries, that is planned to occur within 5 weeks after the Screening Visit, as determined and clearly documented by the Principal Investigator or physician Sub-Investigator (MD/DO). Patients undergoing a proximal revascularization may be enrolled as long as their procedure also includes treating the distal SFA, popliteal or tibial arteries. The EVR must be confirmed as technically successful (a completed procedure where haemostasis has been achieved) before the patient is randomised.
- Normal inflow into the lower extremity as determined by the Principal Investigator or physician Sub-Investigator (MD/DO). Adequacy of inflow can be assessed by hemodynamic measures, angiography or other imaging modalities obtained during Screening or recorded in the medical records up to 30 days prior to the Screening Visit or as defined by imaging at the time of the procedure. A patient with inadequate inflow at the time of Screening can still be enrolled if the inflow is addressed and resolved by the planned revascularization procedure.
- Diagnosis of PAD confirmed by history and any one of the following observed in the index (intervention) leg at the Screening Visit:
Key exclusion criteria (29 listed)
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- Revascularisation planned only to treat proximal (inflow) disease in the iliac and/or common femoral arteries.
- Previous randomisation in the present study.
- Participation in another clinical study with an investigational product within the last 3 months or any new clinical trial during the course of this study.
- Gangrene or ischemic ulcer of either lower extremity.
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 |
|---|---|---|
| TicagrelorAlso: BrilintaAntiplatelet therapy approved for ACS. Antagonist of P2Y12 and inhibitor of adenosine diphosphate (ADP)-induced platelet aggregation. | Drug | Ticagrelor |
| ComparatorAlso: AspirinAspirin monotherapy anti-platelet treatment for PAD patients following EVR procedures | Drug | Aspirin |
Primary outcome
Change From Baseline in Log Transformed Peak Walking Time (PWT) at Week 26 or Early Termination (ET)
Time frame: 26 Weeks
1 secondary outcome
Change From Baseline in Log Transformed Claudication Onset Time (COT) at Week 26 or Early Termination (ET)
Time frame: 26 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29629845Rogers RK, Hiatt WR, Patel MR, Shishehbor MH, White R, Khan ND, Bhalla NP, Jones WS, Low Wang CC. Ticagrelor in Peripheral Artery Disease Endovascular Revascularization (TI-PAD): Challenges in clinical trial execution. Vasc Med. 2018 Dec;23(6):513-522. doi: 10.1177/1358863X18760996. Epub 2018 Apr 9.
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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.
William Hiatt, MD principal investigator
Colorado Prevention Center Clinical Research
10 sites 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 and Comparator in people with Peripheral Artery Disease (PAD), run by AstraZeneca at 10 sites in United States.
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 8 inclusion and 29 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: stopped early, as of the sponsor's last update on 19 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. 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. 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?
Yes. Results are posted in the registry (first posted 14 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change From Baseline in Log Transformed Peak Walking Time (PWT) at Week 26 or Early Termination (ET) (time frame: 26 Weeks). 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 NCT02227368, 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 19 Jul 2017.