Angioplasty, Transluminal, Percutaneous Coronary, Coronary Arteriosclerosis, Peripheral Arteriosclerosis
Conditions
Keywords
Closure Device, Angiography, Angioplasty, Hemostasis, Heart Catheterization, Peripheral Angiography, Femoral Closure, Vascular Closure, Coronary Angiography
Brief summary
The purpose of this study is to determine whether the Ensure Medical Vascular Closure Device is more effective than standard manual compression at sealing the puncture made in the femoral artery following a cardiac or peripheral diagnostic or interventional procedure while maintaining the same level of safety.
Detailed description
Achieving hemostasis at the arterial puncture site after percutaneous cardiac catheterization is a potential cause of bleeding, hematomas, pseudoaneurysms, and various other vascular complications. Hemostasis at the femoral artery access site after diagnostic or interventional procedures is typically achieved using either manual compression or the deployment of a vascular closure device. Manual compression is time consuming for the health-care provider, and painful for the patient. In addition, prolonged periods of immobilization and bed rest may be required. Vascular closure devices have been developed to avoid manual compression, shorten bed rest, and allow earlier ambulation. The Ensure Medical Vascular Closure device (VCD) is intended for femoral artery puncture site closure in patients who have undergone coronary or peripheral diagnostic or interventional procedure using a standard 6F introducer sheath. The device is comprised of a bio-absorbable plug and a plug delivery system. The plug delivery system is designed to position the bio-absorbable plug to the extravascular surface of the femoral artery access site, facilitating a hemostasis response. The Ensure Medical VCD has been studied in a prior feasibility trial of 149 patients, which demonstrated that: (1) the device could be used to successfully obtain rapid hemostasis and early ambulation in patients undergoing catheterization procedures; and (2) the low incidence and relatively minor nature of the observed closure related complications suggests that the device is safe for its intended purpose. The ECLIPSE Trial is designed to evaluate the safety and effectiveness of the Ensure Medical VCD in comparison to standard manual compression. Patients will be randomly assigned to have their arterial access site closed using either manual compression or the VCD. The principal comparisons of the two closure techniques will include: * Time required to obtain hemostasis of the vascular access site * Time required for the patient to ambulate after their catheterization * Frequency of occurrence of serious closure-related complications
Interventions
OTHERManual Compression
Manual compression
DEVICEVascular Closure Device
Investigational vascular closure device
Sponsors
Cordis US Corp.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Scheduled for a coronary or peripheral diagnostic or interventional procedure * Able to undergo emergent vascular surgery if a complication requires it * 6F arterial puncture located in the common femoral artery * Femoral artery has a lumen diameter of at least 5 mm
Exclusion criteria
* Arterial puncture in the femoral artery of both legs * Prior target artery closure with any vascular closure device, or closure with manual compression within 30 days prior to catheterization * Patients who bruise or bleed easily or with a history of significant bleeding or platelet disorders * Acute ST-elevation myocardial infarction within 48 hours prior to catheterization * Uncontrolled hypertension at time of vessel closure * Elevated Activated Clotting Time at time of vessel closure * Ineligible for in-catheterization lab introducer sheath removal * Concurrent participation in another investigational device or drug trial * Thrombolytic therapy, bivalirudin, other thrombin-specific anticoagulants, or low molecular weight heparin within 24 hours prior to catheterization * Preexisting hematoma, arteriovenous fistula, or pseudoaneurysm at the vessel access site prior to femoral artery closure * Prior femoral vascular surgery or vascular graft in region of access site * Femoral artery is tortuous or requires an introducer sheath longer than 11 cm * Fluoroscopically visible calcium, atherosclerotic disease, or stent within 1 cm of the puncture site that would interfere with the operation of the experimental device * Difficulty in obtaining vascular access resulting in multiple arterial punctures and/or posterior arterial puncture * Antegrade vascular puncture * Body Mass Index over 40 kg/m\^2 * Symptomatic leg ischemia in the target limb including severe claudication or weak/absent pulse * Femoral artery diameter stenosis exceeding 50% * Pre-existing severe non-cardiac systemic disease or terminal illness * Planned arterial access at the same access site within 30 days of catheterization * Extended hospitalization (e.g. Coronary Artery Bypass Graft (CABG) surgery) * Pre-existing systemic or cutaneous infection * Prior use of an intra-aortic balloon pump through the arterial access site * Cardiogenic shock during or immediately following the catheterization * Patient is unable to ambulate at baseline * Patient is known or suspected to be pregnant or is lactating * Patient is unavailable for follow-up * Any angiographic or clinical evidence that the physician feels would place the patient at increased risk with the use of the experimental device
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Hemostasis (TTH) | From when the introducer sheath was removed to the time hemostasis was first observed | Time to hemostasis is defined as time (in minutes) from when the introducer sheath was removed to the time that hemostasis was first observed during post-procedure follow up. Hemostasis is defined as no or minimal subcutaneous oozing and the absence of expanding or developing hematoma. Time to hemostasis is one of the two co-primary endpoints. |
| Time to Ambulation (TTA) | From when the introducer sheath was removed to 30 days post-procedure | Time to ambulation is defined as the time from when the introducer sheath was removed to the time that ambulation was achieved. Ambulation is defined as patient standing and walking at least 20 feet without re-bleeding or significant oozing requiring manual compression. Time to ambulation is one of the two co-primary endpoints. |
| Percentage of Patients Who Experience Any Vascular Closure Related Major Adverse Events During the 30 Days Post-procedure | From post-procedure to 30 days follow up | Vascular closure related major adverse events consist of any of the events below: Vascular repair or the need for repair; access site-related bleeding requiring transfusion; access site-related infection requiring intravenous/intramuscular antibiotics and/or extended hospitalization; any new ipsilateral lower extremity ischemia documented by symptoms, physical exam, and/or decreased or absent blood flow on lower extremity angiogram; surgery for access site-related nerve injury; and Permanent (\> 30 days) access site-related nerve injury. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Achieved Device Success Within Five Minutes Post-procedure | Within 5 minutes post-procedure | Device Success is defined as the successful deployment of the plug, initial hemostasis time less or equal to 5 minutes, and removal of the intact delivery system. |
| Time to Eligibility for Hospital Discharge | From introducer sheath removal to hospital discharge, up to 284 hours | Time to Eligibility for Hospital Discharge is measured from the time of sheath removal to the time when the patient is eligible for discharge according to the judgment of the patient's physician. |
| Percentage of Patients Who Experienced Any Other Vascular Closure Related Adverse Events | From end of vessel closure procedure to 30 days post-procedure | Other known vascular closure related adverse events include: Rebleeding Following Initial Hemostasis; Access Site Hematoma \>= 6cm; Access Site-Related Bleeding Requiring \> 30 min for Hemostasis; Transient Access Site-Related Nerve Injury; Retroperitonea Bleeding; Decrease in Pedal Pulse |
| Percent of Patients Who Achieved Procedure Success During 30 Days Post-procedure | From catheterization procedure to 30 day post-procedure follow up | Procedure success is defined as initial hemostasis achieved by the assigned method Vascular Closure Device (VCD) or Manual compression (MC) with none of the primary safety endpoint's closure related major adverse events (MAE). Procedural success is assessed on day of catheterization procedure and at 30 days post-procedure. |
| Time to Hospital Discharge | From introducer sheath removal to patient discharge | Time to hospital discharge is defined as from the time of sheath removal to the time of hospital discharge |
| Time to Device Deployment, up to 5 Minutes | From device inserted to introducer sheath removal | Time to device deployment is defined as from the time device inserted to the time sheath removed |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Roll-In Roll-In patients were device training patients | 87 |
| Vascular Closure Device Ensure Medical Vascular Closure Device (VCD) have been developed to avoid manual compression, shorten bed rest, and allow earlier ambulation. | 267 |
| Manual Compression Traditionally Hemostasis at the femoral artery access site after diagnostic or interventional procedures is typically achieved using either manual compression (with or without the use of adjunctive mechanical compression devices) | 134 |
| Total | 488 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 7 | 4 |
| Overall Study | Other reasons | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Roll-In | Vascular Closure Device | Manual Compression | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 40 Participants | 123 Participants | 51 Participants | 214 Participants |
| Age, Categorical Between 18 and 65 years | 47 Participants | 144 Participants | 83 Participants | 274 Participants |
| Age Continuous | 63.3 years STANDARD_DEVIATION 11.61 | 63.3 years STANDARD_DEVIATION 11.13 | 61.4 years STANDARD_DEVIATION 10.47 | 62.8 years STANDARD_DEVIATION 11.05 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 7 Participants | 8 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 84 Participants | 260 Participants | 126 Participants | 470 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 8 Participants | 5 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 23 Participants | 13 Participants | 46 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 77 Participants | 236 Participants | 114 Participants | 427 Participants |
| Region of Enrollment United States | 87 participants | 267 participants | 134 participants | 488 participants |
| Sex: Female, Male Female | 29 Participants | 85 Participants | 51 Participants | 165 Participants |
| Sex: Female, Male Male | 58 Participants | 182 Participants | 83 Participants | 323 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 87 | 24 / 267 | 6 / 134 |
| serious Total, serious adverse events | 0 / 87 | 0 / 267 | 0 / 134 |
Outcome results
Primary
Percentage of Patients Who Experience Any Vascular Closure Related Major Adverse Events During the 30 Days Post-procedure
Vascular closure related major adverse events consist of any of the events below: Vascular repair or the need for repair; access site-related bleeding requiring transfusion; access site-related infection requiring intravenous/intramuscular antibiotics and/or extended hospitalization; any new ipsilateral lower extremity ischemia documented by symptoms, physical exam, and/or decreased or absent blood flow on lower extremity angiogram; surgery for access site-related nerve injury; and Permanent (\> 30 days) access site-related nerve injury.
Time frame: From post-procedure to 30 days follow up
Population: Intent to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roll-In | Percentage of Patients Who Experience Any Vascular Closure Related Major Adverse Events During the 30 Days Post-procedure | 0 Percentage of participants |
| Vascular Closure Device | Percentage of Patients Who Experience Any Vascular Closure Related Major Adverse Events During the 30 Days Post-procedure | 0 Percentage of participants |
| Manual Compression | Percentage of Patients Who Experience Any Vascular Closure Related Major Adverse Events During the 30 Days Post-procedure | 0 Percentage of participants |
Comparison: Based on pre-planned hypotheses, a minimum sample size of 390 randomized patients (260 VCD patients and 130 MC patients) would demonstrate non-inferiority for the primary safety endpoint and superiority for both co-primary effectiveness endpoints in comparing VCD vs. MC.p-value: 0.0006unconditional exact test
Primary
Time to Ambulation (TTA)
Time to ambulation is defined as the time from when the introducer sheath was removed to the time that ambulation was achieved. Ambulation is defined as patient standing and walking at least 20 feet without re-bleeding or significant oozing requiring manual compression. Time to ambulation is one of the two co-primary endpoints.
Time frame: From when the introducer sheath was removed to 30 days post-procedure
Population: Intent to Treat (ITT)Population with non-missing time to ambulation data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roll-In | Time to Ambulation (TTA) | 1.98 Hours | Standard Deviation 2.59 |
| Vascular Closure Device | Time to Ambulation (TTA) | 2.54 Hours | Standard Deviation 5.02 |
| Manual Compression | Time to Ambulation (TTA) | 6.24 Hours | Standard Deviation 13.34 |
Comparison: Null hypothesis:The mean time to ambulation for the manual compression (MC) arm is less or equal to that for the vascular closure device (VCD) arm.~The trial is powered to detect a 5 minute reduction in mean time to hemostasis and a 2 hour reduction in mean time to ambulation for VCD vs. MC with over 90% power and a 5% two-sided (2.5% one-sided) Type I errorp-value: 0.002895% CI: [-5.53, -1.87]t-test, 2 sided
Primary
Time to Hemostasis (TTH)
Time to hemostasis is defined as time (in minutes) from when the introducer sheath was removed to the time that hemostasis was first observed during post-procedure follow up. Hemostasis is defined as no or minimal subcutaneous oozing and the absence of expanding or developing hematoma. Time to hemostasis is one of the two co-primary endpoints.
Time frame: From when the introducer sheath was removed to the time hemostasis was first observed
Population: Intent to treat population (ITT) with non-missing time to hemostasis data. ITT population consists of all randomized (VCD and MC) patients where a femoral artery closure procedure is attempted post-randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roll-In | Time to Hemostasis (TTH) | 4.68 Minutes | Standard Deviation 19.37 |
| Vascular Closure Device | Time to Hemostasis (TTH) | 4.38 Minutes | Standard Deviation 11.59 |
| Manual Compression | Time to Hemostasis (TTH) | 20.05 Minutes | Standard Deviation 22.54 |
Comparison: Null hypothesis: The mean time to hemostasis for the manual compression (MC) arm is less or equal to that for the vascular closure device (VCD) arm.~The trial is powered to detect a 5 minute reduction in mean time to hemostasis and a 2 hour reduction in mean time to ambulation for VCD vs. MC with over 90% power and a 5% two-sided (2.5% one-sided) Type I errorp-value: <0.000195% CI: [-19.04, -12.31]t-test, 2 sided
Secondary
Percentage of Patients Who Achieved Device Success Within Five Minutes Post-procedure
Device Success is defined as the successful deployment of the plug, initial hemostasis time less or equal to 5 minutes, and removal of the intact delivery system.
Time frame: Within 5 minutes post-procedure
Population: Intent to treat population (ITT) excluding the Manual Compression (MC) patients since MC Patients didn't deploy the device.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roll-In | Percentage of Patients Who Achieved Device Success Within Five Minutes Post-procedure | 95.4 Percentage of participants |
| Vascular Closure Device | Percentage of Patients Who Achieved Device Success Within Five Minutes Post-procedure | 89.1 Percentage of participants |
Secondary
Percentage of Patients Who Experienced Any Other Vascular Closure Related Adverse Events
Other known vascular closure related adverse events include: Rebleeding Following Initial Hemostasis; Access Site Hematoma \>= 6cm; Access Site-Related Bleeding Requiring \> 30 min for Hemostasis; Transient Access Site-Related Nerve Injury; Retroperitonea Bleeding; Decrease in Pedal Pulse
Time frame: From end of vessel closure procedure to 30 days post-procedure
Population: Intent to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roll-In | Percentage of Patients Who Experienced Any Other Vascular Closure Related Adverse Events | 10.3 Percentage of participants |
| Vascular Closure Device | Percentage of Patients Who Experienced Any Other Vascular Closure Related Adverse Events | 8.99 Percentage of participants |
| Manual Compression | Percentage of Patients Who Experienced Any Other Vascular Closure Related Adverse Events | 4.48 Percentage of participants |
Secondary
Percent of Patients Who Achieved Procedure Success During 30 Days Post-procedure
Procedure success is defined as initial hemostasis achieved by the assigned method Vascular Closure Device (VCD) or Manual compression (MC) with none of the primary safety endpoint's closure related major adverse events (MAE). Procedural success is assessed on day of catheterization procedure and at 30 days post-procedure.
Time frame: From catheterization procedure to 30 day post-procedure follow up
Population: Intent to Treat Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roll-In | Percent of Patients Who Achieved Procedure Success During 30 Days Post-procedure | 95.4 Percentage of participants |
| Vascular Closure Device | Percent of Patients Who Achieved Procedure Success During 30 Days Post-procedure | 91.8 Percentage of participants |
| Manual Compression | Percent of Patients Who Achieved Procedure Success During 30 Days Post-procedure | 91.0 Percentage of participants |
Comparison: Null hypothesis: The percentages of patients achieving procedure success between the vascular closure device and manual compression arms are equal.p-value: 0.8595% CI: [-4.8, 7.4]t-test, 2 sided
Secondary
Time to Device Deployment, up to 5 Minutes
Time to device deployment is defined as from the time device inserted to the time sheath removed
Time frame: From device inserted to introducer sheath removal
Population: Intent to Treat population with non-missing time data, excluding MC patients. Patients in the MC arm didn't deploy the device.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roll-In | Time to Device Deployment, up to 5 Minutes | 0.94 Hour | Standard Deviation 1.13 |
| Vascular Closure Device | Time to Device Deployment, up to 5 Minutes | 1.01 Hour | Standard Deviation 2.12 |
Secondary
Time to Eligibility for Hospital Discharge
Time to Eligibility for Hospital Discharge is measured from the time of sheath removal to the time when the patient is eligible for discharge according to the judgment of the patient's physician.
Time frame: From introducer sheath removal to hospital discharge, up to 284 hours
Population: Intent to treat population with non-missing time data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roll-In | Time to Eligibility for Hospital Discharge | 9.72 Hour | Standard Deviation 14.15 |
| Vascular Closure Device | Time to Eligibility for Hospital Discharge | 12.57 Hour | Standard Deviation 13.91 |
| Manual Compression | Time to Eligibility for Hospital Discharge | 16.25 Hour | Standard Deviation 27.49 |
Comparison: Null hypothesis: The mean time to eligibility for hospital discharge for the manual compression (MC) arm is equal to that for the vascular closure device (VCD) arm.p-value: 0.15495% CI: [-7.84, 0.45]t-test, 2 sided
Secondary
Time to Hospital Discharge
Time to hospital discharge is defined as from the time of sheath removal to the time of hospital discharge
Time frame: From introducer sheath removal to patient discharge
Population: Intent to Treat population with non-missing time data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roll-In | Time to Hospital Discharge | 13.64 Hour | Standard Deviation 18.54 |
| Vascular Closure Device | Time to Hospital Discharge | 16.77 Hour | Standard Deviation 19.79 |
| Manual Compression | Time to Hospital Discharge | 19.35 Hour | Standard Deviation 29.23 |
Comparison: Null hypothesis: The mean time to hospital discharge for the manual compression (MC) arm is equal to that for the vascular closure device (VCD) arm.p-value: 0.361295% CI: [-7.46, 2.31]t-test, 2 sided