Critical Limb Ischemia, Peripheral Artery Disease
Conditions
Keywords
Peripheral Artery Disease, Critical Limb Ischemia, Orbital Atherectomy, Balloon Angioplasty, Intravascular Ultrasound (IVUS), Fractional Flow Reserve (FFR)
Brief summary
CLARITY I is a pilot study to identify the clinically appropriate endpoint(s) of a larger, statistically powered pivotal trial for treatment of patients with Critical Limb Ischemia (CLI).
Detailed description
This prospective, randomized, multi-center, post-market study of approximately 50 subjects randomized 1:1 to Orbital Atherectomy (OA) performed with Cardiovascular Systems, Inc.'s Orbital Atherectomy System (OAS) followed by adjunctive balloon angioplasty (BA) vs. BA alone for treatment of tibial vessel disease, defined as ≥ 50 % stenosis of the anterior tibial (AT), posterior tibial (PT), tibial peroneal trunk (TPT), or peroneal (PR) arteries by angiography. All subjects will have a corresponding wound being fed by the target vessel which will be assessed during the study. Subjects will be followed to one year.
Interventions
DEVICEOrbital Atherectomy System
Orbital atherectomy (OA) is performed prior to adjunctive balloon angioplasty (BA)
DEVICEBalloon Angioplasty
Type of balloon selected is driven by preference of the operator.
Sponsors
Abbott Medical Devices
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria: 1. Subject's age ≥ 18 years. 2. Subject is an acceptable candidate for percutaneous intervention with the Sponsor's OAS and BA in accordance with their labeled indications and instructions for use. 3. Subject is willing and able to sign an approved informed consent form (ICF). 4. Subject is willing and able to attend follow-up and wound care visits. General
Exclusion criteria
1. Subject is pregnant or planning to become pregnant within the study period. 2. Subject is currently participating in an investigational drug or other device study that can clinically interfere with the endpoints of this trial. 3. Subject has a known sensitivity to contrast media and the sensitivity cannot be adequately pre-medicated. 4. Uncontrolled allergy to nitinol, stainless steel, or other stent materials. 5. Subject has known allergy to atherectomy lubricant components such as soybean oil, egg yolk phospholipids, glycerin or sodium hydroxide. 6. Subject has a history of bleeding diathesis or coagulopathy or will refuse blood transfusions. 7. Subject has been diagnosed with chronic renal failure or has a creatinine level \> 2.5, unless on dialysis, prior to the index treatment. 8. Subject has evidence of intracranial or gastrointestinal bleeding within 90 days. 9. Subject has a history of trauma, fracture, major surgery (includes major amputation), or biopsy of a parenchymal organ within past 14 days, or patient has not healed from a previous medical intervention occurring more than 14 days. 10. Subject has a history of stroke or myocardial infarction (MI) within 90 days prior to enrollment in the study. 11. Subject has a planned major surgery (includes major amputation) scheduled within 60 days after treatment of the index limb. 12. Subject has a planned interventional treatment to address stenosis of the contralateral limb scheduled within 60 days after the index treatment. 13. Subject has a planned interventional treatment to address inflow stenosis of the ipsilateral limb scheduled within 60 days after the index treatment. 14. Inflow or bilateral PAD requiring treatment prior to enrollment was not successfully treated, defined as \> 50% residual stenosis and/or occurrence of procedural angiographic complications, excluding dissection types A and B. 15. Subject has previously had their other limb treated as part of the study. Angiographic Inclusion Criteria: 1. Target lesion(s) located in the anterior tibial (AT), posterior tibial (PT), tibial peroneal trunk (TPT) or peroneal (PR) arteries. 2. Target lesion has ≥ 50 % stenosis by angiography. 3. Subject has a corresponding wound being fed by the target vessel. Angiographic
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fibrofatty Plaque Area as Assessed by IVUS | Pre-intervention, and post-balloon angioplasty | The pre- (Pre-Tx) and post-treatment (Post-Tx) fibrofatty plaque area. A positive value equates to a decrease in fibrofatty plaque area. |
| Percentage of Calcium Removal Out of Lumen Gain as Assessed by IVUS | Post-balloon angioplasty | The post-treatment percentage of calcium removal out of lumen gain at the maximum calcium ablation site. A positive value equates to reduction in calcium out of the lumen gain. |
| Change in Minimum Lumen Area Percent Stenosis as Assessed by IVUS | Pre-intervention, and post-balloon angioplasty | The pre- (Pre-Tx) and post-treatment (Post-Tx) minimum lumen area percent stenosis. A positive value equates to a decrease in lumen area percent stenosis. |
| Change in Plaque Area as Assessed by IVUS | Pre-intervention, and post-balloon angioplasty | The pre- (Pre-Tx) and post-treatment (Post-Tx) plaque area. A positive value equates to a decrease in plaque area. |
| Change in Dense Calcium Area as Assessed by IVUS | Pre-intervention, and post-balloon angioplasty | The pre- (Pre-Tx) and post-treatment (Post-Tx) dense calcium area. A positive value equates to a decrease in dense calcium area. |
| Change in Necrotic Core Area as Assessed by IVUS | Pre-intervention, and post-balloon angioplasty | The pre- (Pre-Tx) and post-treatment (Post-Tx) necrotic core area. A positive value equates to a decrease necrotic core area. |
| Change in Fibrous Plaque Area as Assessed by IVUS | Pre-intervention, and post-balloon angioplasty | The pre- (Pre-Tx) and post-treatment (Post-Tx) fibrous plaque area. A positive value equates to a decrease in fibrous plaque area. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fractional Flow Reserve | Post-orbital atherectomy (OA arm only) and post-balloon angioplasty (both arms) | Fractional flow reserve (FFR) will be measured to assess hemodynamic function following each device procedure. During FFR, adenosine will be given through the femoral artery sheath or access catheter in two doses: 600 mcg and 1200 mcg. A higher FFR is presumed to correlate to better flow which may improve wound healing. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Orbital Atherectomy System Orbital Atherectomy (OA) is performed prior to adjunctive Balloon Angioplasty (BA) Orbital Atherectomy System: Orbital atherectomy (OA) is performed prior to adjunctive balloon angioplasty (BA) Balloon Angioplasty: Type of balloon selected is driven by preference of the operator. | 25 |
| Balloon Angioplasty Balloon Angioplasty (BA) alone Balloon Angioplasty: Type of balloon selected is driven by preference of the operator. | 26 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 2 |
| Overall Study | Lost to Follow-up | 6 | 5 |
| Overall Study | Withdrawal by Subject | 4 | 6 |
Baseline characteristics
| Characteristic | Orbital Atherectomy System | Balloon Angioplasty | Total |
|---|---|---|---|
| Age, Continuous | 65.3 years STANDARD_DEVIATION 11.3 | 69.4 years STANDARD_DEVIATION 12.4 | 67.4 years STANDARD_DEVIATION 11.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 3 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 23 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Number of treated lesions | 26 lesions | 26 lesions | 52 lesions |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 8 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 18 Participants | 35 Participants |
| Region of Enrollment United States | 25 participants | 26 participants | 51 participants |
| Sex: Female, Male Female | 3 Participants | 12 Participants | 15 Participants |
| Sex: Female, Male Male | 22 Participants | 14 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 25 | 3 / 26 |
| other Total, other adverse events | 4 / 25 | 8 / 26 |
| serious Total, serious adverse events | 22 / 25 | 17 / 26 |
Outcome results
Primary
Change in Dense Calcium Area as Assessed by IVUS
The pre- (Pre-Tx) and post-treatment (Post-Tx) dense calcium area. A positive value equates to a decrease in dense calcium area.
Time frame: Pre-intervention, and post-balloon angioplasty
Population: Not all subjects had reported IVUS data for each lesion pre- and post-treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Orbital Atherectomy System | Change in Dense Calcium Area as Assessed by IVUS | Pre-Tx, dense calcium area (mm^3/mm) | 0.7 area (mm^3/mm) |
| Orbital Atherectomy System | Change in Dense Calcium Area as Assessed by IVUS | Post-Tx, dense calcium area (mm^3/mm) | 0.4 area (mm^3/mm) |
| Balloon Angioplasty | Change in Dense Calcium Area as Assessed by IVUS | Pre-Tx, dense calcium area (mm^3/mm) | 1.0 area (mm^3/mm) |
| Balloon Angioplasty | Change in Dense Calcium Area as Assessed by IVUS | Post-Tx, dense calcium area (mm^3/mm) | 1.1 area (mm^3/mm) |
Comparison: Null hypothesis: no difference in populations for post-balloon angioplasty dense calcium area.p-value: 0.3573Wilcoxon (Mann-Whitney)
Primary
Change in Fibrofatty Plaque Area as Assessed by IVUS
The pre- (Pre-Tx) and post-treatment (Post-Tx) fibrofatty plaque area. A positive value equates to a decrease in fibrofatty plaque area.
Time frame: Pre-intervention, and post-balloon angioplasty
Population: Not all subjects had reported IVUS data for each lesion pre- and post-treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Orbital Atherectomy System | Change in Fibrofatty Plaque Area as Assessed by IVUS | Pre-Tx, fibrofatty plaque area (mm^3/mm) | 0.2 area (mm^3/mm) |
| Orbital Atherectomy System | Change in Fibrofatty Plaque Area as Assessed by IVUS | Post-Tx, fibrofatty plaque area (mm^3/mm) | 0.2 area (mm^3/mm) |
| Balloon Angioplasty | Change in Fibrofatty Plaque Area as Assessed by IVUS | Pre-Tx, fibrofatty plaque area (mm^3/mm) | 0.1 area (mm^3/mm) |
| Balloon Angioplasty | Change in Fibrofatty Plaque Area as Assessed by IVUS | Post-Tx, fibrofatty plaque area (mm^3/mm) | 0.1 area (mm^3/mm) |
Comparison: Null hypothesis: no difference in populations for post-balloon angioplasty fibrofatty plaque area.p-value: 0.0579Wilcoxon (Mann-Whitney)
Primary
Change in Fibrous Plaque Area as Assessed by IVUS
The pre- (Pre-Tx) and post-treatment (Post-Tx) fibrous plaque area. A positive value equates to a decrease in fibrous plaque area.
Time frame: Pre-intervention, and post-balloon angioplasty
Population: Not all subjects had reported IVUS data for each lesion pre- and post-treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Orbital Atherectomy System | Change in Fibrous Plaque Area as Assessed by IVUS | Post-Tx, fibrous plaque area (mm^3/mm) | 1.4 area (mm^3/mm) |
| Orbital Atherectomy System | Change in Fibrous Plaque Area as Assessed by IVUS | Pre-Tx, fibrous plaque area (mm^3/mm) | 1.7 area (mm^3/mm) |
| Balloon Angioplasty | Change in Fibrous Plaque Area as Assessed by IVUS | Pre-Tx, fibrous plaque area (mm^3/mm) | 1.0 area (mm^3/mm) |
| Balloon Angioplasty | Change in Fibrous Plaque Area as Assessed by IVUS | Post-Tx, fibrous plaque area (mm^3/mm) | 0.9 area (mm^3/mm) |
Comparison: Null hypothesis: no difference in populations for post-balloon angioplasty fibrous plaque area.p-value: 0.2149Wilcoxon (Mann-Whitney)
Primary
Change in Minimum Lumen Area Percent Stenosis as Assessed by IVUS
The pre- (Pre-Tx) and post-treatment (Post-Tx) minimum lumen area percent stenosis. A positive value equates to a decrease in lumen area percent stenosis.
Time frame: Pre-intervention, and post-balloon angioplasty
Population: Not all subjects had reported IVUS data for each lesion pre- and post-treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Orbital Atherectomy System | Change in Minimum Lumen Area Percent Stenosis as Assessed by IVUS | Pre-Tx, minimum area stenosis (%) | 43.8 percent of minimum area stenosis |
| Orbital Atherectomy System | Change in Minimum Lumen Area Percent Stenosis as Assessed by IVUS | Post-Tx, minimum area stenosis (%) | 36.4 percent of minimum area stenosis |
| Balloon Angioplasty | Change in Minimum Lumen Area Percent Stenosis as Assessed by IVUS | Pre-Tx, minimum area stenosis (%) | 45.2 percent of minimum area stenosis |
| Balloon Angioplasty | Change in Minimum Lumen Area Percent Stenosis as Assessed by IVUS | Post-Tx, minimum area stenosis (%) | 31.5 percent of minimum area stenosis |
Comparison: Null hypothesis: no difference in populations for post-balloon angioplasty minimum lumen area stenosis.p-value: 0.6228t-test, 2 sided
Primary
Change in Necrotic Core Area as Assessed by IVUS
The pre- (Pre-Tx) and post-treatment (Post-Tx) necrotic core area. A positive value equates to a decrease necrotic core area.
Time frame: Pre-intervention, and post-balloon angioplasty
Population: Not all subjects had reported IVUS data for each lesion pre- and post-treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Orbital Atherectomy System | Change in Necrotic Core Area as Assessed by IVUS | Pre-Tx, necrotic core area (mm^3/mm) | 0.7 area (mm^3/mm) |
| Orbital Atherectomy System | Change in Necrotic Core Area as Assessed by IVUS | Post-Tx, necrotic core area (mm^3/mm) | 0.8 area (mm^3/mm) |
| Balloon Angioplasty | Change in Necrotic Core Area as Assessed by IVUS | Pre-Tx, necrotic core area (mm^3/mm) | 0.9 area (mm^3/mm) |
| Balloon Angioplasty | Change in Necrotic Core Area as Assessed by IVUS | Post-Tx, necrotic core area (mm^3/mm) | 1.0 area (mm^3/mm) |
Comparison: Null hypothesis: no difference in populations for post-balloon angioplasty necrotic core area.p-value: 0.6073Wilcoxon (Mann-Whitney)
Primary
Change in Plaque Area as Assessed by IVUS
The pre- (Pre-Tx) and post-treatment (Post-Tx) plaque area. A positive value equates to a decrease in plaque area.
Time frame: Pre-intervention, and post-balloon angioplasty
Population: Not all subjects had reported IVUS data for each lesion pre- and post-treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Orbital Atherectomy System | Change in Plaque Area as Assessed by IVUS | Pre-Tx, plaque area (mm^3/mm) | 6.5 area (mm^3/mm) |
| Orbital Atherectomy System | Change in Plaque Area as Assessed by IVUS | Post-Tx, plaque area (mm^3/mm) | 6.3 area (mm^3/mm) |
| Balloon Angioplasty | Change in Plaque Area as Assessed by IVUS | Pre-Tx, plaque area (mm^3/mm) | 6.0 area (mm^3/mm) |
| Balloon Angioplasty | Change in Plaque Area as Assessed by IVUS | Post-Tx, plaque area (mm^3/mm) | 6.0 area (mm^3/mm) |
Comparison: Null hypothesis: no difference in populations for post-balloon angioplasty plaque area.p-value: 0.4528Wilcoxon (Mann-Whitney)
Primary
Percentage of Calcium Removal Out of Lumen Gain as Assessed by IVUS
The post-treatment percentage of calcium removal out of lumen gain at the maximum calcium ablation site. A positive value equates to reduction in calcium out of the lumen gain.
Time frame: Post-balloon angioplasty
Population: Not all subjects had reported IVUS data for each lesion pre- and post-treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Orbital Atherectomy System | Percentage of Calcium Removal Out of Lumen Gain as Assessed by IVUS | 25.0 percentage of lumen gain |
| Balloon Angioplasty | Percentage of Calcium Removal Out of Lumen Gain as Assessed by IVUS | 0.0 percentage of lumen gain |
Comparison: Null hypothesis: no difference in populations for post-balloon angioplasty reduction of calcium out of lumen gain.p-value: 0.022Wilcoxon (Mann-Whitney)
Secondary
Fractional Flow Reserve
Fractional flow reserve (FFR) will be measured to assess hemodynamic function following each device procedure. During FFR, adenosine will be given through the femoral artery sheath or access catheter in two doses: 600 mcg and 1200 mcg. A higher FFR is presumed to correlate to better flow which may improve wound healing.
Time frame: Post-orbital atherectomy (OA arm only) and post-balloon angioplasty (both arms)
Population: Some sites were exempt from performing FFR. Not all subjects had available FFR.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Orbital Atherectomy System | Fractional Flow Reserve | Post final balloon: FFR w/ 1200 mcg adenosine | 0.87 Ratio (proximal/distal pressure) | Standard Deviation 0.1 |
| Orbital Atherectomy System | Fractional Flow Reserve | Post final OAS: FFR w/ 600 mcg adenosine | 0.83 Ratio (proximal/distal pressure) | Standard Deviation 0.14 |
| Orbital Atherectomy System | Fractional Flow Reserve | Post final OAS: FFR with 1200 mcg adenosine | 0.80 Ratio (proximal/distal pressure) | Standard Deviation 0.12 |
| Orbital Atherectomy System | Fractional Flow Reserve | Post final balloon: FFR w/ 600 mcg adenosine | 0.90 Ratio (proximal/distal pressure) | Standard Deviation 0.13 |
| Balloon Angioplasty | Fractional Flow Reserve | Post final balloon: FFR w/ 600 mcg adenosine | 0.75 Ratio (proximal/distal pressure) | Standard Deviation 0.22 |
| Balloon Angioplasty | Fractional Flow Reserve | Post final OAS: FFR with 1200 mcg adenosine | NA Ratio (proximal/distal pressure) | — |
| Balloon Angioplasty | Fractional Flow Reserve | Post final balloon: FFR w/ 1200 mcg adenosine | 0.76 Ratio (proximal/distal pressure) | Standard Deviation 0.24 |
| Balloon Angioplasty | Fractional Flow Reserve | Post final OAS: FFR w/ 600 mcg adenosine | NA Ratio (proximal/distal pressure) | — |
Comparison: Null hypothesis: no difference in populations for post-final balloon FFR value with 600 mcg adenosine.p-value: 0.076t-test, 2 sided
Comparison: Null hypothesis: no difference in populations for post-final balloon FFR value with 1200 mcg adenosine.p-value: 0.205t-test, 2 sided