Establishing the Microcirculatory Effects of Ticagrelor on Tissue Perfusion in Critical Limb Ischemia

• Sponsor: The Cleveland Clinic (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02230527
• Collaborator: (none)
• Enrollment: 46
• Location: 1
• Arms: 2
• Actual Duration (Months): 67
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Peripheral Arterial Disease	Drug: Ticagrelor; Drug: Clopidogrel	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Establishing the Microcirculatory Effects of Ticagrelor on Tissue Perfusion in Critical Limb Ischemia
• Actual Study Start Date: Oct 1, 2014
• Actual Primary Completion Date: May 1, 2020
• Actual Study Completion Date: May 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Clopidogrel Clopidogrel 75mg by mouth daily	Drug: Clopidogrel; 75mg once a day by mouth; Other Names: Plavix
Experimental: Ticagrelor Ticagrelor 90mg by mouth twice daily	Drug: Ticagrelor; 90mg twice a day by mouth; Other Names: Brilinta Brilique Possia

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts 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 -

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• The Cleveland Clinic

Investigators

• Principal Investigator: Joseph Campbell, MD, The Cleveland Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 21, 2017

More Information

Publications

None provided.

• Responsible Party: Joseph Campbell, Principal Investigator, The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT02230527
• Other Study ID Numbers: 14-799
• First Posted: Sep 3, 2014
• Last Update Posted: Jul 7, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Peripheral Arterial Disease; Peripheral Vascular Diseases; Ischemia; Clopidogrel; Ticagrelor

Study Results

Participant Flow

Arm/Group Title	Clopidogrel	Ticagrelor
Arm/Group Description	Clopidogrel 75mg by mouth daily Clopidogrel: 75mg once a day by mouth	Ticagrelor 90mg by mouth twice daily Ticagrelor: 90mg twice a day by mouth
Period Title: Overall Study
STARTED	23	23
COMPLETED	18	21
NOT COMPLETED	5	2

Baseline Characteristics

Arm/Group Title	Clopidogrel	Ticagrelor	Total
Arm/Group Description	Clopidogrel 75mg by mouth daily Clopidogrel: 75mg once a day by mouth	Ticagrelor 90mg by mouth twice daily Ticagrelor: 90mg twice a day by mouth	Total of all reporting groups
Overall Participants	23	23	46
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.4 (11.8)	67.2 (8.9)	66.8 (10.3)
Sex: Female, Male (Count of Participants)
Female	10 43.5%	5 21.7%	15 32.6%
Male	13 56.5%	18 78.3%	31 67.4%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	11 47.8%	15 65.2%	26 56.5%
Asian	1 4.3%	0 0%	1 2.2%
African American/Black	11 47.8%	8 34.8%	19 41.3%
Past/Current Smoker (Count of Participants)
Count of Participants [Participants]	18 78.3%	16 69.6%	34 73.9%
History of Hypertension (Count of Participants)
Count of Participants [Participants]	20 87%	20 87%	40 87%
History of Diabetes (Count of Participants)
Count of Participants [Participants]	17 73.9%	15 65.2%	32 69.6%
History of Hyperlipidemia (Count of Participants)
Count of Participants [Participants]	20 87%	18 78.3%	38 82.6%

Outcome Measures

1. Primary Outcome

Title	Absolute Change in TcPO2 From Baseline to Month 6
Description	The primary endpoint is the absolute change in TcPO2 from baseline to month 6 compared between treatment groups.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Patients with baseline and TCPO2 data available at 6 months

Arm/Group Title	Clopidogrel	Ticagrelor
Arm/Group Description	Clopidogrel 75mg by mouth daily Clopidogrel: 75mg once a day by mouth	Ticagrelor 90mg by mouth twice daily Ticagrelor: 90mg twice a day by mouth
Measure Participants	16	15
Mean (Standard Deviation) [mmHG]	14.9 (17.8)	4.2 (19.9)

Adverse Events

Time Frame	Through 6 months
Adverse Event Reporting Description	Serious adverse events
Arm/Group Title	Clopidogrel		Ticagrelor
Arm/Group Description	Clopidogrel 75mg by mouth daily Clopidogrel: 75mg once a day by mouth		Ticagrelor 90mg by mouth twice daily Ticagrelor: 90mg twice a day by mouth
All Cause Mortality
	Clopidogrel		Ticagrelor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/23 (4.3%)		0/23 (0%)
Serious Adverse Events
	Clopidogrel		Ticagrelor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/23 (21.7%)		6/23 (26.1%)
Blood and lymphatic system disorders
Anemia	0/23 (0%)	0	1/23 (4.3%)	1
Cardiac disorders
Stent occlusion	0/23 (0%)	0	1/23 (4.3%)	1
General disorders
Organ failure	1/23 (4.3%)	1	0/23 (0%)	0
Infections and infestations
infection	1/23 (4.3%)	1	2/23 (8.7%)	2
Surgical and medical procedures
Amputation	0/23 (0%)	0	2/23 (8.7%)	2
Vascular disorders
Worsening Limb Ischemia	1/23 (4.3%)	2	3/23 (13%)	3
Limb pain/ulcer	2/23 (8.7%)	2	4/23 (17.4%)	4
Other (Not Including Serious) Adverse Events
	Clopidogrel		Ticagrelor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/23 (13%)		9/23 (39.1%)
Cardiac disorders
Junctional rhythm	1/23 (4.3%)	1	0/23 (0%)	0
Infections and infestations
Osteomyelitis	0/23 (0%)	0	1/23 (4.3%)	1
Renal and urinary disorders
UTI	1/23 (4.3%)	1	0/23 (0%)	0
Kidney stone	0/23 (0%)	0	1/23 (4.3%)	1
Respiratory, thoracic and mediastinal disorders
Shortness of breath	1/23 (4.3%)	1	7/23 (30.4%)	7
Dyspnea	0/23 (0%)	0	1/23 (4.3%)	1
Vascular disorders
Foot ulcer	0/23 (0%)	0	1/23 (4.3%)	1
Excessive bruising	0/23 (0%)	0	1/23 (4.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.