Peripheral Arterial Disease
Conditions
Brief summary
This is a single center, prospective, randomized, unblinded, open-label, active controlled pilot study to evaluate the efficacy and safety of ticagrelor plus aspirin versus clopidogrel plus aspirin in patients with Rutherford Stage IV to VI PAD that have undergone a percutaneous transluminal angioplasty (PTA) of the lower extremities in the past 2 weeks.
Detailed description
Enrollment into the study will require severe symptomatic CLI without wounds (Rutherford Stage IV) or CLI with concomitant vascular insufficiency wounds (Rutherford Stage V-VI PAD). Potential participants will be identified and screened prior to discharge or at the time of the first out-patient visit (within 2 weeks after discharge) after a percutaneous lower extremity arterial angiography with arterial intervention (stent or balloon angioplasty) for the presence of lower extremity vascular insufficiency. Participants will be classified as Rutherford Class IV - VI (with or without ulcerations). A total of 60 patients will be randomized into 2 treatment groups in a 1:1 ratio (ticagrelor to clopidogrel). Patients are placed on clopidogrel after their arterial intervention per standard of care. They will remain on clopidogrel up to the time that randomization occurs. For patients that are randomized to ticagrelor, the clopidogrel will be stopped. Patients will be randomized to either ticagrelor 90mg by mouth twice daily or clopidogrel 75mg by mouth daily.
Interventions
DRUGTicagrelor
90mg twice a day by mouth
DRUGClopidogrel
75mg once a day by mouth
Sponsors
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Adults age 18-100 years with Rutherford Classification Stage IV through VI PAD with a recent percutaneous lower extremity arterial angiography with arterial intervention in the past 2 weeks 2. Willingness to sign informed consent 3. Ability to return for follow up visits 4. A female patient of childbearing potential who is sexually active must agree to use adequate contraception from screening until 30 days after receiving the last dose of study drug. Women not of childbearing potential are defined as those who have surgically sterilized (hysterectomy, bilateral oophorectomy, or tubal ligation) or who are post menopausal (defined as at least 2 years since last regular menses). The female patient should not be lactating and must have a negative pregnancy test at screening.
Exclusion criteria
Patients will be ineligible for this study if they meet any one of the following criteria: 1. Intolerance to thienopyridines 2. Hypersensitivity to ticagrelor or any component of the product. 3. Concomitant use of oral anticoagulation with vitamin K antagonist, factor Xa inhibitor, or direct thrombin inhibitor 4. History of intracranial hemorrhage 5. History of severe hepatic impairment defined by baseline transaminase greater than or equal to 3x ULN or any elevation in bilirubin 6. Active bleeding 7. Allergy to aspirin 8. Baseline TcPO2 \< 10 mmHg post angiography 9. Resting, pre- procedure heart rate \<50 beats-per-minute without a permanent pacemaker and not on an atrioventricular nodal blocking agent 10. Severe COPD on home oxygen therapy -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in TcPO2 From Baseline to Month 6 | 6 months | The primary endpoint is the absolute change in TcPO2 from baseline to month 6 compared between treatment groups. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Clopidogrel Clopidogrel 75mg by mouth daily
Clopidogrel: 75mg once a day by mouth | 23 |
| Ticagrelor Ticagrelor 90mg by mouth twice daily
Ticagrelor: 90mg twice a day by mouth | 23 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Ticagrelor | Total | Clopidogrel |
|---|---|---|---|
| Age, Continuous | 67.2 years STANDARD_DEVIATION 8.9 | 66.8 years STANDARD_DEVIATION 10.3 | 66.4 years STANDARD_DEVIATION 11.8 |
| History of Diabetes | 15 Participants | 32 Participants | 17 Participants |
| History of Hyperlipidemia | 18 Participants | 38 Participants | 20 Participants |
| History of Hypertension | 20 Participants | 40 Participants | 20 Participants |
| Past/Current Smoker | 16 Participants | 34 Participants | 18 Participants |
| Race/Ethnicity, Customized African American/Black | 8 Participants | 19 Participants | 11 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 15 Participants | 26 Participants | 11 Participants |
| Sex: Female, Male Female | 5 Participants | 15 Participants | 10 Participants |
| Sex: Female, Male Male | 18 Participants | 31 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 23 | 0 / 23 |
| other Total, other adverse events | 3 / 23 | 9 / 23 |
| serious Total, serious adverse events | 5 / 23 | 6 / 23 |
Outcome results
Primary
Absolute Change in TcPO2 From Baseline to Month 6
The primary endpoint is the absolute change in TcPO2 from baseline to month 6 compared between treatment groups.
Time frame: 6 months
Population: Patients with baseline and TCPO2 data available at 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clopidogrel | Absolute Change in TcPO2 From Baseline to Month 6 | 14.9 mmHG | Standard Deviation 17.8 |
| Ticagrelor | Absolute Change in TcPO2 From Baseline to Month 6 | 4.2 mmHG | Standard Deviation 19.9 |