Cilostazol After Lower Extremity Arterial Revascularization Trial (CLEAR)

• ClinicalTrials.gov Identifier: NCT02374957
• Recruitment Status: Terminated
• First Posted: March 2, 2015
• Results First Posted: November 23, 2018
• Last Update Posted: November 23, 2018
• Sponsor: Wake Forest University Health Sciences
• Information provided by (Responsible Party): Wake Forest University Health Sciences

Study Description

Brief Summary:

Twenty patients will be recruited to CLEAR. Ten will be randomized to the treatment arm (Cilostazol) and tenwill be randomized to the control group. Patients randomized to the treatment arm will receive Cilostazol for 90 days. The primary purpose of this study is to collect quality of life data on patients undergoing peripheral revascularization in order to determine the sample size required to adequately power a trial of Cilostazol versus usual care without Cilostazol and its effect on quality of life.

Condition or disease	Intervention/treatment	Phase
Peripheral Arterial Disease; Claudication (Finding)	Drug: Cilostazol	Phase 4

Detailed Description:

Cilostazol is the only medication approved for use in peripheral arterial disease (PAD) patients to reduce claudication symptoms. Contemporary data has demonstrated that Cilostazol improves patency after endovascular interventions in multiple randomized trials and retrospective studies done in Japan in both critical limb ischemia and claudication patients. However, Cilostazol use after peripheral revascularization has been sporadic and there has been no research to estimate patient quality of life with use of Cilostazol after open or endovascular lower extremity revascularization.

This is a prospective investigator initiated single-center open-label, non-placebo controlled pilot study. Eligible patients would be randomized to either the Cilostazol treatment or the non-Cilostazol treatment groups using a closed envelope randomization technique. Twenty patients will be recruited and randomized; Ten to the treatment group and tento the control group.

The primary purpose of this pilot study is to collect quality of life data on patients undergoing peripheral revascularization in order to determine the sample size required for adequate powered trial of Cilostazol versus usual care without Cilostazol and its effect on Quality of Life.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Cilostazol After Lower Extremity Arterial Revascularization Trial (CLEAR)
• Study Start Date: February 2015
• Actual Primary Completion Date: June 30, 2017
• Actual Study Completion Date: June 30, 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Cilostazol; Administer Cilostazol100 mg twice daily for 90 days.	Drug: Cilostazol; 100 mg twice daily for 90 days; Other Name: Pletal
No Intervention: Control; No Cilostazol

Outcome Measures

Primary Outcome Measures :

1. Change in Quality of Life in Relation to Use of Cilostazol After Lower Extremity Revascularization (EQ-5D Sum Score) at 6 Weeks [ Time Frame: Baseline and 6 weeks. ]
   The Euroqol 5D (EQ5D) questionnaire will be completed at baseline, six weeks and three months follow-up. Cross-sectional and change scores will be used to project sample size requirements for a full trial. The EuroQol (EQ-5D) questionnaire is a standardized instrument for measuring generic health status. The descriptive system consists of the following five dimensions: 1) mobility, 2) self-care, 3) usual activities, 4) pain/discomfort, 5 anxiety/depression. Each participant was asked to choose one level that reflects their own health state today for each of the five dimensions. The EQ5D sum score is a composite sum of the individual dimension scores. Values of the total score can range from 5 to 25 with higher scores indicating a worse health state. Separate change scores are estimated at each follow-up time point.
2. Change in Quality of Life in Relation to Use of Cilostazol After Lower Extremity Revascularization (EQ-5D Sum Score) at 3 Months [ Time Frame: Baseline and 3 months ]
   The Euroqol 5D (EQ5D) questionnaire will be completed at baseline, six weeks and three months follow-up. Cross-sectional and change scores will be used to project sample size requirements for a full trial. The EuroQol (EQ-5D) questionnaire is a standardized instrument for measuring generic health status. . The descriptive system consists of the following five dimensions: 1) mobility, 2) self-care, 3) usual activities, 4) pain/discomfort, 5 anxiety/depression. Each participant was asked to choose one level that reflects their own health state today for each of the five dimensions. The EQ5D sum score is a composite sum of the individual dimension scores. Values of the total score can range from 5 to 25 with higher scores indicating a worse health state. Separate change scores are estimated at each follow-up time point.
3. Change in Quality of Life in Relation to Use of Cilostazol After Lower Extremity Revascularization (Euroqol-5D Visual Analog) at 6 Weeks. [ Time Frame: Baseline and Six Weeks ]

   The Euroqol 5D (EQ5D) questionnaire will be completed at baseline, six weeks and three months follow-up. Cross-sectional and change scores will be used to project sample size requirements for a full trial. The EuroQol (EQ-5D) questionnaire is a standardized instrument for measuring generic health status. The second part of the Euroqol-5D is a analog scale with endpoints labeled "best imaginable health state" and "worst imaginable health state" with 0 representing worst health state and 100 representing best health state. Participants choose which number best represents their health on that day. Separate change scores are estimated at each follow-up time point.

   Higher numbers are better.

4. Change in Quality of Life in Relation to Use of Cilostazol After Lower Extremity Revascularization (Euroqol-5D Visual Analog) at 3 Months. [ Time Frame: Baseline and 3 months ]

   The Euroqol 5D (EQ5D) questionnaire will be completed at baseline, six weeks and three months follow-up. Cross-sectional and change scores will be used to project sample size requirements for a full trial. The EuroQol (EQ-5D) questionnaire is a standardized instrument for measuring generic health status. The second part of the Euroqol-5D is a analog scale with endpoints labeled "best imaginable health state" and "worst imaginable health state" with 0 representing worst health state and 100 representing best health state. Participants choose which number best represents their health on that day. Separate change scores are estimated at each follow-up time point.

   Higher numbers are better.

5. Change in Quality of Life Scores - Estimation of Ambulatory Capacity by History-Questionnaire (EACH-Q) at 6 Weeks [ Time Frame: Baseline and Six Weeks ]

   The quality of life instrument EACH Q questionnaire was administered at baseline, 6-week and 3-month follow-up visits. Cross-sectional and change scores will be used to project sample size requirements for a full trial. The EACH-Q is a four-item questionnaire that estimates the maximum duration that patients can maintain different displacement speeds, ranging from "slow walk" to "running." Values of the total score can range from 0 to 100 with higher scores indicating a better health state. Separate change scores are estimated at each follow-up time point.

   With the EACH-Q higher scores are better.

6. Change in Quality of Life Scores - Estimation of Ambulatory Capacity by History-Questionnaire (EACH-Q) at 3 Months [ Time Frame: Baseline and 3 months ]

   The quality of life instrument EACH Q questionnaire was administered at baseline, 6-week and 3-month follow-up visits. Cross-sectional and change scores will be used to project sample size requirements for a full trial. The EACH-Q is a four-item questionnaire that estimates the maximum duration that patients can maintain different displacement speeds, ranging from "slow walk" to "running." Values of the total score can range from 0 to 100 with higher scores indicating a better health state. Separate change scores are estimated at each follow-up time point.

   With the EACH-Q higher scores are better.

Secondary Outcome Measures :

1. Graft Patency, Determined as Opened or Occluded by Duplex Scan Post-intervention. [ Time Frame: 13 days to 259 days ]
   Graft patency was determined by duplex scan as opened or occluded. Follow-up duplex testing ranged from 13 days to 259 days. Number of patency failures (i.e., graft occlusions) are shown below by treatment arm.

Other Outcome Measures:

1. Number of Participants Affected by Death [ Time Frame: 90 days ]
   Number of Participants affected by Death was reported
2. Patients Who Had Amputations Following Initial Procedure. [ Time Frame: 90 days ]
   Patients who went on to have amputations following initial procedure
3. Number of Participants Who Had a Stroke [ Time Frame: 90 days ]
   Secondary outcome measure - patients who had a stroke during the 90 day follow up period.
4. Claudication Symptoms and Rest Pain. [ Time Frame: 90 days ]
   Secondary outcome measures including claudication symptoms and rest pain.

Eligibility Criteria

• Ages Eligible for Study: 35 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• At least 35 years of age
• Atherosclerotic peripheral arterial disease
• Able to provide informed consent
• Lower extremity open or endovascular revascularization.

Exclusion Criteria:

• Known CHF (class III/IV)
• Allergic reaction to phosphodiasterase inhibitors
• Intracranial bleeding within 3 months or active bleeding peptic ulcer disease
• Traumatic vascular injuries requiring revascularization
• Pregnant or breast feeding women or women who plan to get pregnant over the study period
• Planned ipsilateral major amputation within 30 days of index procedure
• Moderate to severe hepatic impairment.

Contacts and Locations

Locations

United States, North Carolina

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States, 27106

Sponsors and Collaborators

Wake Forest University Health Sciences

Investigators

• Principal Investigator: Matthew Edwards, MD; Wake Forest University Health Sciences

  Study Documents (Full-Text)

Documents provided by Wake Forest University Health Sciences:

Study Protocol and Statistical Analysis Plan  [PDF] October 24, 2018

More Information

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT02374957
• Other Study ID Numbers: IRB00030275
• First Posted: March 2, 2015
• Results First Posted: November 23, 2018
• Last Update Posted: November 23, 2018
• Last Verified: November 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Wake Forest University Health Sciences:

leg pain; claudication

Additional relevant MeSH terms:

Peripheral Arterial Disease; Peripheral Vascular Diseases; Intermittent Claudication; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Cilostazol; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Vasodilator Agents; Neuroprotective Agents; Protective Agents; Phosphodiesterase 3 Inhibitors; Phosphodiesterase Inhibitors; Enzyme Inhibitors