Peripheral Artery DiseasePhase 3NCT02325466
Comparative Efficacy of Ticagrelor Versus Aspirin on Blood Viscosity in Peripheral Artery Disease Patients With Type 2 Diabetes
A Phase 3 study testing Aspirin and Ticagrelor in people with Peripheral Artery Disease and Type 2 Diabetes, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial summary
The hypothesis being that both aspirin-ticagrelor and ticagrelor monotherapy will be superior to aspirin monotherapy in the reduction of whole blood viscosity at the end of each 4 week treatment period. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Peripheral Artery Disease, Type 2 Diabetes
- What is being tested?
- Aspirin and Ticagrelor
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2015to 4 May 2018
- Phase
- Phase 3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female or male aged ≥ 35 years
- Type 2 diabetes mellitus
- Symptomatic PAD
- Ankle-brachial index ≤ 0.85 or calcified blood vessels with toe-brachial index ≤ 0.6 and/or abnormal post-exercise ankle-brachial index
- Prior surgical or percutaneous intervention of the peripheral arteries ≥12 months previously with a residual stenoses of ≥50% in a non-dilated artery.
Who cannot join
- Subject is pregnant or breast-feeding
- Planned revascularization or amputation
- Known bleeding disorder
- History of intracranial hemorrhag3
- Considered at risk of hemorrhagic events
- Hypersensitivity or allergic reactions to aspirin
Show all 16Show fewer
- Concomitant use of anticoagulants such as warfarin, dabigatran, factor Xa inhibitors or antiplatelet drugs such as clopidogrel, dipyridamole and sulfapyridine
- Subject has a condition or circumstance which would prevent them from adhering to treatment regimens
- Subject has active infection
- Subject has an anemia
- Subject has given blood or received a blood transfusion at any point during the study
- Subject has polycythemia vera or any hyperviscosity syndrome
- Subjects with Waldenstrom's macroglobulinemia who have an increased risk of hyperviscosity syndrome
- Subject has history of severe liver disease, obstructive liver disease such as primary biliary cirrhosis or end-stage renal disease (eGFR <30 mL/min/m2)
- Family members or employees of the investigator or study centers involved in the study
- Subject has poor diabetes or hypertension control (systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 100 mmHg)
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: Comparative Efficacy of Ticagrelor Versus Aspirin on Blood Viscosity in Peripheral Artery Disease (PAD) Patients With Type 2 Diabetes (T2D)
The hypothesis being that both aspirin-ticagrelor and ticagrelor monotherapy will be superior to aspirin monotherapy in the reduction of whole blood viscosity at the end of each 4 week treatment period. Study participants will be randomized into 3 groups, and each group will receive each of 3 treatments in the cross-over study. At the end of each individual 4 week treatment period the investigators will determine whether there are differences in low and high shear rate dependent viscosity and investigate the effect of the treatment on peripheral arterial blood flow using pulse volume recordings, ankle brachial index and toe pressures. Subjects will be eligible if they have ankle-brachial index less than or equal to 0.85, or if a patient's blood vessels are calcified, patients will have toe-brachial index less than or equal to 0.6 performed using continuous-wave Doppler.
Read the detailed description
Ticagrelor has been shown to significantly reduce the rate of cardiovascular disease (CVD) events and death compared with clopidogrel in patients having prior acute coronary syndrome. A number of outcome studies have demonstrated the risk of major CVD events increased with blood viscosity. Stroke patients and those with stroke risk factors were shown to have chronically elevated blood viscosity relative to healthy controls. Based on prior observations, the rationale for this study is to demonstrate that both aspirin-ticagrelor and ticagrelor monotherapy will be superior to aspirin monotherapy in the reduction of whole blood viscosity at the end of each 4 week treatment period.
The primary objectives for this study is to: (1) Compare the effect of aspirin-ticagrelor with aspirin in a double blind, randomized, cross-over study design (weeks 1-4, weeks 6-10, and weeks 12-16) on blood viscosity at both low (5 s-¹) and high (300 s-¹) shear rates at the end of each 4-week treatment period; and (2) to compare the effect of ticagrelor mono-therapy with aspirin in a double blind, randomized, cross-over study design (weeks 1-4, weeks 6-10, and weeks 12-16) on blood viscosity at both low (5 s-¹) and high (300 s-¹) at the end of each 4-week treatment.
The secondary objectives for this study include: (1) a determination as to whether there are differences in low and high shear rate dependent viscosity with treatment by ticagrelor alone and combination aspirin-ticagrelor. Additionally, investigated will be the effect of the treatment on peripheral arterial blood flow using pulse volume recordings, ankle brachial index, and toe pressures.
The general approach to evaluation of drug efficacy will be through blood samples collected with a standard venipuncture for viscosity testing. Blood viscosity will be measured using an automated scanning capillary tube viscometer across a physiologic range of shear rates of 1-1000 s-1 in increments of 0.1 s-1. Blood viscosity levels at 5 s-1 will be reported as low-shear viscosity, and blood viscosity measurements at 300 s-1 will be reported as high-shear viscosity. Additionally, pulse volume recordings will be simultaneously obtained at the level of the ankle, metatarsal and toe bilaterally according to standard protocol, and Continuous-wave Doppler will be used to determine ankle-brachial indices or toe-brachial indices, and flow velocity profiles.
- Conditions
- Peripheral Artery Disease, Type 2 Diabetes
- Being tested
- Aspirin, Ticagrelor, Aspirin Placebo, Ticagrelor Placebo
- Keywords
- Peripheral Artery Disease, Type 2 Diabetes, Blood Viscosity, Ticagrelor, Aspirin
- Medical subject headings
- Peripheral Arterial Disease, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
Also called ASA
Aspirin 81mg
TicagrelorDrug
ticagrelor 90 mg
Aspirin PlaceboDrug
Also called Placebo
Ticagrelor PlaceboDrug
Also called Placebo
| Study group | Role | What they receive |
|---|---|---|
| Aspirin/Ticagrelor placebo | Placebo comparator | aspirin 81 mg daily and ticagrelor placebo twice daily Receives: Drug: Aspirin; Drug: Ticagrelor Placebo |
| Aspirin/Ticagrelor | Active comparator | aspirin 81 mg daily and ticagrelor 90 mg twice daily Receives: Drug: Aspirin; Drug: Ticagrelor |
| Aspirin Placebo/Ticagrelor | Active comparator | aspirin placebo daily and ticagrelor 90 mg twice daily Receives: Drug: Ticagrelor; Drug: Aspirin Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change in Low Shear Blood Viscosity
Compare the effect of aspirin-ticagrelor and ticagrelor monotherapy with aspirin on blood viscosity from week 16 to baseline
Measured: baseline, week 16
Mean Change in High Shear Blood Viscosity
Compare the effect of aspirin-ticagrelor and ticagrelor monotherapy with aspirin on blood viscosity at week 16 to baseline
Measured: baseline and week 16
Secondary outcomes (2)
Mean Change in Peripheral Arterial Blood Flow
Measure of treatment effect using pulse volume recordings of the ankle, great toe and brachial artery to calculate the ankle brachial index (ABI) and toe brachial index (TBI) at week 16 compared to baseline.
ABI and TBI are taken in order to determine the existence and severity of peripheral arterial disease.
ABI - The normal range for the ankle-brachial index is between 0.90 and 1.30. ABI <0.90 is abnormal: 0.41 to 0.90 indicates mild to moderate peripheral artery disease; 0.40 and lower indicates severe disease. The lower the index, the higher the chances of leg pain while exercising or limb-threatening low blood flow.
TBI ≥ 0.7 is normal, TBI < 0.7 is abnormal.
Measured: baseline and week 16
Mean Change in Microvascular Blood Flow Composite Score
Measure of treatment effect using pulse volume recordings of the ankle, great toe and brachial artery to calculate the ankle brachial index and toe pressures composite score at week 16 from baseline. Composite score obtained by adding all the measurements and averaged. The score was tested by the Laser Doppler Flowmetry (LDF). Minimum score is 0 which mean no blood flow detected and there is no maximum value of the score, and higher score mean better blood flow.
Measured: baseline and week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Dec 2014 (estimated)
- Study startApr 2015
- Primary completion4 May 2018
- Study completion4 May 2018
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 DiseaseStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe 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
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robert Rosenson, Icahn School of Medicine at Mount Sinai
- Investigators
- Robert Rosenson, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02325466
- Sponsor's protocol ID
- GCO 13-1925
- Status last verified
- Mar 2022
- First submitted
- 19 Dec 2014
- Last updated
- 21 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Rosenson RS, Chen Q, Najera SD, Krishnan P, Lee ML, Cho DJ. Ticagrelor improves blood viscosity-dependent microcirculatory flow in patients with lower extremity arterial disease: the Hema-kinesis clinical trial. Cardiovasc Diabetol. 2019 Jun 7;18(1):77. doi: 10.1186/s12933-019-0882-5.
PubMed 31174526
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Efficacy of Ticagrelor Versus Aspirin on Blood Viscosity in Peripheral Artery Disease (PAD) Patients With Type 2 Diabetes (T2D)
- ClinicalTrials.gov ID
- NCT02325466
- Acronym / sponsor ID
- GCO 13-1925
- Conditions
- Peripheral Artery Disease, Type 2 Diabetes
- Keywords
- Peripheral Artery Disease, Type 2 Diabetes, Blood Viscosity, Ticagrelor, Aspirin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Study start
- Apr 2015
- Primary completion
- 4 May 2018 (actual)
- Study completion
- 4 May 2018 (actual)
- First posted
- 25 Dec 2014 (estimated)
- Results
- Posted 21 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The hypothesis being that both aspirin-ticagrelor and ticagrelor monotherapy will be superior to aspirin monotherapy in the reduction of whole blood viscosity at the end of each 4 week treatment period. Study participants will be randomized into 3 groups, and each group will receive each of 3 treatments in the cross-over study. At the end of each individual 4 week treatment period the investigators will determine whether there are differences in low and high shear rate dependent viscosity and investigate the effect of the treatment on peripheral arterial blood flow using pulse volume recordings, ankle brachial index and toe pressures. Subjects will be eligible if they have ankle-brachial index less than or equal to 0.85, or if a patient's blood vessels are calcified, patients will have toe-brachial index less than or equal to 0.6 performed using continuous-wave Doppler.
Detailed description
Ticagrelor has been shown to significantly reduce the rate of cardiovascular disease (CVD) events and death compared with clopidogrel in patients having prior acute coronary syndrome. A number of outcome studies have demonstrated the risk of major CVD events increased with blood viscosity. Stroke patients and those with stroke risk factors were shown to have chronically elevated blood viscosity relative to healthy controls. Based on prior observations, the rationale for this study is to demonstrate that both aspirin-ticagrelor and ticagrelor monotherapy will be superior to aspirin monotherapy in the reduction of whole blood viscosity at the end of each 4 week treatment period.
The primary objectives for this study is to: (1) Compare the effect of aspirin-ticagrelor with aspirin in a double blind, randomized, cross-over study design (weeks 1-4, weeks 6-10, and weeks 12-16) on blood viscosity at both low (5 s-¹) and high (300 s-¹) shear rates at the end of each 4-week treatment period; and (2) to compare the effect of ticagrelor mono-therapy with aspirin in a double blind, randomized, cross-over study design (weeks 1-4, weeks 6-10, and weeks 12-16) on blood viscosity at both low (5 s-¹) and high (300 s-¹) at the end of each 4-week treatment.
The secondary objectives for this study include: (1) a determination as to whether there are differences in low and high shear rate dependent viscosity with treatment by ticagrelor alone and combination aspirin-ticagrelor. Additionally, investigated will be the effect of the treatment on peripheral arterial blood flow using pulse volume recordings, ankle brachial index, and toe pressures.
The general approach to evaluation of drug efficacy will be through blood samples collected with a standard venipuncture for viscosity testing. Blood viscosity will be measured using an automated scanning capillary tube viscometer across a physiologic range of shear rates of 1-1000 s-1 in increments of 0.1 s-1. Blood viscosity levels at 5 s-1 will be reported as low-shear viscosity, and blood viscosity measurements at 300 s-1 will be reported as high-shear viscosity. Additionally, pulse volume recordings will be simultaneously obtained at the level of the ankle, metatarsal and toe bilaterally according to standard protocol, and Continuous-wave Doppler will be used to determine ankle-brachial indices or toe-brachial indices, and flow velocity profiles.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Aspirin/Ticagrelor placebo | Placebo comparator | Drug: Aspirin, Drug: Ticagrelor Placeboaspirin 81 mg daily and ticagrelor placebo twice daily |
| Aspirin/Ticagrelor | Active comparator | Drug: Aspirin, Drug: Ticagreloraspirin 81 mg daily and ticagrelor 90 mg twice daily |
| Aspirin Placebo/Ticagrelor | Active comparator | Drug: Ticagrelor, Drug: Aspirin Placeboaspirin placebo daily and ticagrelor 90 mg twice daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Female or male aged ≥ 35 years
- Type 2 diabetes mellitus
- Symptomatic PAD
- Ankle-brachial index ≤ 0.85 or calcified blood vessels with toe-brachial index ≤ 0.6 and/or abnormal post-exercise ankle-brachial index
- Prior surgical or percutaneous intervention of the peripheral arteries ≥12 months previously with a residual stenoses of ≥50% in a non-dilated artery.
Key exclusion criteria (16 listed)
- Subject is pregnant or breast-feeding
- Planned revascularization or amputation
- Known bleeding disorder
- History of intracranial hemorrhag3
- Considered at risk of hemorrhagic events
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 |
|---|---|---|
| AspirinAlso: ASAAspirin 81mg | Drug | Aspirin/Ticagrelor, Aspirin/Ticagrelor placebo |
| Ticagrelorticagrelor 90 mg | Drug | Aspirin Placebo/Ticagrelor, Aspirin/Ticagrelor |
| Aspirin PlaceboAlso: Placebo | Drug | Aspirin Placebo/Ticagrelor |
| Ticagrelor PlaceboAlso: Placebo | Drug | Aspirin/Ticagrelor placebo |
Primary outcome
Mean Change in Low Shear Blood Viscosity
Time frame: baseline, week 16
Compare the effect of aspirin-ticagrelor and ticagrelor monotherapy with aspirin on blood viscosity from week 16 to baseline
Mean Change in High Shear Blood Viscosity
Time frame: baseline and week 16
Compare the effect of aspirin-ticagrelor and ticagrelor monotherapy with aspirin on blood viscosity at week 16 to baseline
2 secondary outcomes
Mean Change in Peripheral Arterial Blood Flow
Time frame: baseline and week 16
Mean Change in Microvascular Blood Flow Composite Score
Time frame: baseline and week 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31174526Rosenson RS, Chen Q, Najera SD, Krishnan P, Lee ML, Cho DJ. Ticagrelor improves blood viscosity-dependent microcirculatory flow in patients with lower extremity arterial disease: the Hema-kinesis clinical trial. Cardiovasc Diabetol. 2019 Jun 7;18(1):77. doi: 10.1186/s12933-019-0882-5.
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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.
Robert Rosenson, MD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Aspirin and Ticagrelor in people with Peripheral Artery Disease and Type 2 Diabetes, run by Icahn School of Medicine at Mount Sinai at 1 site 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 5 inclusion and 16 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: finished, as of the sponsor's last update on 21 Mar 2022. 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 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. 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 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?
Yes. Results are posted in the registry (first posted 21 Mar 2022). 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?
Mean Change in Low Shear Blood Viscosity (time frame: baseline, week 16). The study lists 2 primary outcomes in all. 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 NCT02325466, 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 21 Mar 2022.