Clinical trial NCT02325466: Comparative Efficacy of Ticagrelor Versus Aspirin on Blood Viscosity in Peripheral Artery Disease Patients With Type 2 Diabetes
Official title: Comparative Efficacy of Ticagrelor Versus Aspirin on Blood Viscosity in Peripheral Artery Disease (PAD) Patients With Type 2 Diabetes (T2D)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Peripheral Artery Disease
Type 2 Diabetes
Keywords: Peripheral Artery Disease
Type 2 Diabetes
Blood Viscosity
Ticagrelor
Aspirin
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2014-12-25
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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
* 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)

Primary outcomes:
measure: Mean Change in Low Shear Blood Viscosity
timeFrame: baseline, week 16
measure: Mean Change in High Shear Blood Viscosity
timeFrame: baseline and week 16
Secondary outcomes:
measure: Mean Change in Peripheral Arterial Blood Flow
timeFrame: baseline and week 16
measure: Mean Change in Microvascular Blood Flow Composite Score
timeFrame: baseline and week 16
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Robert Rosenson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.