Walking Effect of Long Term Ticagrelor in Subjects With PAD Who Have Undergone EVR

NCT02227368 | Terminated Phase 2 Results

• 1 other identifier: D5135L00003
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 10

Brief 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 pain.

Conditions

Peripheral Artery Disease (PAD)

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; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Actions; Physiological Effects of Drugs; Fibrinolytic Agents; Crardiovascular Agents

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Log Transformed Peak Walking Time (PWT) at Week 26 or Early Termination (ET)

  26 Weeks

Secondary Outcomes (1)

• Change From Baseline in Log Transformed Claudication Onset Time (COT) at Week 26 or Early Termination (ET)

  26 Weeks

Study Arms (2)

Ticagrelor

EXPERIMENTAL

26 Weeks of ticagrelor 90mg twice a day plus aspirin placebo once daily

Drug: Ticagrelor

Aspirin

ACTIVE COMPARATOR

26 Weeks of aspirin 100mg once daily plus ticagrelor placebo twice a day

Drug: Comparator

Interventions

Ticagrelor DRUG

Antiplatelet therapy approved for ACS. Antagonist of P2Y12 and inhibitor of adenosine diphosphate (ADP)-induced platelet aggregation.

Also known as: Brilinta

Ticagrelor

Comparator DRUG

Aspirin monotherapy anti-platelet treatment for PAD patients following EVR procedures

Also known as: Aspirin

Aspirin

Eligibility Criteria

• Age: 50 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• CPC Clinical Research: collaborator

Study Sites (10)

Research Site

Daytona Beach, Florida, 32114, United States

Location

Research Site

Jacksonville, Florida, 32216, United States

Location

Research Site

Ocala, Florida, 34471, United States

Location

Research Site

Sarasota, Florida, 34239, United States

Location

Research Site

Munster, Indiana, 46321, United States

Location

Research Site

New York, New York, 10001, United States

Location

Research Site

Yonkers, New York, 10701, United States

Location

Research Site

Cleveland, Ohio, 44195, United States

Location

Research Site

McKinney, Texas, 75069, United States

Location

Research Site

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• 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.

  PMID: 29629845 DERIVED

MeSH Terms

Conditions

Peripheral Arterial Disease; Myocardial Infarction; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases

Interventions

Ticagrelor; Aspirin

Condition Hierarchy (Ancestors)

Atherosclerosis; Myocardial Ischemia; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Limitations and Caveats

This study was terminated early for low enrolment. Less than 25% of anticipated number of subjects were enroled and there was an imbanlance between groups. Therefore, the results should be interpreted with caution.

Results Point of Contact

• Title: Naeem Khan, MD
• Organization: AstraZeneca Pharmaceuticals LP

Naeem.Khan@astrazeneca.com

+1 302-885-8976

Study Officials

• William Hiatt, MD

  Colorado Prevention Center Clinical Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2014
• First Posted: August 28, 2014
• Study Start: October 20, 2014
• Primary Completion: May 23, 2016
• Study Completion: May 23, 2016
• Last Updated: July 19, 2017
• Results First Posted: June 14, 2017

Record last verified: 2017-06

Locations

US (10)