Lower-Limb Adventitial Infusion of DexaMethasone Via Bullfrog to Reduce Occurrence of Restenosis After Atherectomy (ATX)-Based Revascularization
- Conditions
- Chronic Limb Ischemia
- Interventions
- Registration Number
- NCT02479620
- Lead Sponsor
- Mercator MedSystems, Inc.
- Brief Summary
This is a prospective, multi-center, randomized pilot study to document the effects of adventitial delivery of dexamethasone after atherectomy-based revascularizations of lesions below the knee in symptomatic patients with critical limb ischemia (CLI).
- Detailed Description
This is a prospective, multi-center, randomized pilot study to document the effects of adventitial delivery of dexamethasone after atherectomy-based revascularizations of lesions below the knee in symptomatic patients with critical limb ischemia (CLI). Up to 120 patients (60 treatment and 60 control), including up to 20 Rutherford 6 patients (10 treatment and 10 control) at up to 30 sites in the United States and Europe. This study will assess the safety and effectiveness of Bullfrog Micro-Infusion Device adventitial deposition of dexamethasone in reducing inflammation and restenosis in patients with clinical evidence of chronic critical limb ischemia with an angiographically significant lesion in the infrapopliteal crural vessels.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 120
Screening Criteria:
- Age ≥18 years
- Patient or patient's legal representative have been informed of the nature of the study, agrees to participate and has signed an IRB/EC approved consent form
- Female patients of childbearing potential have a negative pregnancy test ≤7 days before the procedure and are willing to use a reliable method of birth control for the duration of study participation
- Patient has documented chronic Critical Limb Ischemia (CLI) in the target limb from the popliteal artery to the ankle joint prior to the study procedure with Rutherford Category 4, 5 or 6
- Life expectancy >1 year in the Investigator's opinion
Angiographic Criteria:
- Successful revascularization of the TL with less than 30% residual stenosis, run-off down to the foot and direct in-line flow to any foot wound
- Reference vessel(s) diameter ≥2 mm
- Single or multiple atherosclerotic lesion ≥70% in at least one infrapopliteal crural target vessel including the tibioperoneal trunk that totals up to 30 cm in length (with no greater than 5 cm length of contiguous intervening normal artery), with possible extension into the popliteal artery distal to the center of the knee joint space (the P3 segment)
Screening Criteria:
- Patient unwilling or unlikely to comply with visit schedule
- Planned major index limb amputation
- Active foot infection; however, osteomyelitis in the toes or mild cellulitis around the perimeter of gangrene or small ulcers are not exclusions, but osteomyelitis of the metatarsal or more proximal region would be exclusionary
- Inability to receive study medications
- Estimated glomerular filtration rate (eGFR) less than 30 mL/min, except for patients with end stage renal disease on chronic hemodialysis
- Stage 3 (per SVS WIfI classification) or worse heel ulcers or heel ulcers that are determined to be primarily neuropathic in nature
Angiographic/Procedural Criteria:
- Hemodynamically significant inflow lesion (≥50% DS) or occlusion in the ipsilateral iliac, SFA, or popliteal arteries in which there is failure to successfully treat and obtain a <30% residual stenosis
- Target lesion length is >25 cm as measured from proximal normal vessel to distal normal vessel
- Total length of lesions treated during the case (including target lesion, inflow lesions, and other non-target lesions) >25 cm
- Lesions revascularized during the index case but untreated by Bullfrog
- Use of alternative therapy, e.g. radiation therapy, as part of the index lesion treatment, or use of any drug eluting stents (DES) or drug-eluting balloon/drug-coated balloons (DEB/DCB) for treatment of any infra-inguinal lesions during the study procedure or during the initial six-month follow up period
- Previously implanted stent in the TL(s)
- Aneurysm in the target vessel
- Acute thrombus in the target limb
- Failure to cross the TL with a guide wire; however, subintimal wire crossing is allowed
- Heavy eccentric or concentric calcification at index lesion, which in the judgment of the investigator would prevent penetration of the Micro-Infusion Device needle through the vessel wall
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dexamethasone Delivery Dexamethasone Sodium Phosphate Injection, USP, 4 mg/mL Up to 60 atherectomy-based revascularization procedures at up to 30 sites in the United States and Europe. For Subjects randomized into the Dexamethasone Delivery arm, this protocol will utilize a 4 mg/mL preparation of Dexamethasone Sodium Phosphate Injection, USP. Each milliliter of the solution contains 4.37 mg of dexamethasone sodium phosphate equivalent to 4 mg of dexamethasone phosphate or 3.33 mg of dexamethasone. The total dose of Dexamethasone Sodium Phosphate Injection, USP will be diluted by 20% prior to infusion. This will result in a final concentration of 3.2 mg dexamethasone phosphate (3.5 mg dexamethasone sodium phosphate, or 2.67 mg dexamethasone) in each milliliter of solution.
- Primary Outcome Measures
Name Time Method Freedom from MALE Up to 6 Months following the procedure Freedom from major adverse limb event (MALE) within 6 months.
Composite clinical safety by freedom from adverse events including death, MALE, major unplanned amputation, or CD-TLR. Up to 6 Months following the procedure Freedom from composite of death within 30 days from the index procedure, MALE, major unplanned amputation or CD-TLR within 6 months.
Freedom from CD-TLR Up to 6 Months following the procedure Freedom from clinically driven target lesion revascularization (CD-TLR) within 6 months.
TVAL% change from post-procedure 6 Months following the procedure Transverse-view vessel area loss percentage (TVAL%) of the target lesion at 6 months by quantitative vascular angiography (QVA) or prior to any CD-TLR of the target lesion before 6 months
- Secondary Outcome Measures
Name Time Method QVA change from post-procedure 6 months following the procedure Improvement in % diameter stenosis (%DSS) of the target lesion (TL) and the maximum late lumen loss for the lesion (LLL) will be assessed by quantitative vascular angiography (QVA).
SVS WIfI score versus baseline 30 days, 6 and 12 months following the procedure Composite clinical safety by freedom from adverse events including death, unplanned amputation, CD-TLR, SAE or MALE. Up to 12 months following the procedure Freedom from composite of death, unplanned amputation and CD-TLR, serious adverse events (SAE) and MALE.
Primary sustained clinical improvement versus baseline 30 days, 6 and 12 months following the procedure Sustained upward shift of at least 1 category on Rutherford classification as compared to baseline without the need for repeated TLR or surgical revascularization in amputation-free surviving subjects.
Walking capacity assessment versus baseline 30 days, 6 and 12 months following the procedure Inflammatory biomarker changes from baseline 24 hours and 30 days Infustion technical success Intra-procedural The grade of distribution (A-F) around infusion sites will be used as a qualitative measure of technical success of adventitial delivery of the drug.
Revascularization success Intra-procedural Establishment of antegrade flow with residual stenosis \<30% by angiogram.
Event-free survival 12 months following the procedure Proportion of patients reaching 12-month endpoint without a composite clinical safety event.
IVUS change from post-procedure 6 months following the procedure Improvement in intravascular ultrasound (IVUS) result with in the TL (subgroup analysis).
Change in foot wounds versus baseline 30 days, 6 and 12 Months following the procedure The number and total size of foot wounds, reduction in number and size of baseline wounds, and occurrence of new wounds (number and size) will be measured against baseline.
Resolved CLI death 30 days, 6 and 12 months following the procedure The rate of deaths in patients who had a resolution of their critical limb ischemia (CLI).
CD-TLR 30 days, 6 and 12 months following the procedure Secondary sustained clinical improvement versus baseline 30 days, 6 and 12 months following the procedure Sustained upward shift of at least 1 category on Rutherford classification as compared to baseline including the need for repeated TLR or surgical revascularization in amputation-free surviving subjects.
EQ5D versus baseline 30 days, 6 and 12 months following the procedure SAE/MALE assessment 30 days, 6 and 12 months following the procedure Healthcare economic analysis From baseline to 24 months An analysis of the economics associated with the care of patients, including number of hospital days throughout the study, return visits and hospitalizations, time from index procedure to required revascularization and number of index-lesion-related readmissions.
Amputation-free survival 30 days, 6 and 12 months following the procedure Percentage of patients reaching the endpoints without major or minor amputation.
Major and minor amputations and amputation level 30 days, 6 and 12 months following the procedure Percentage of patients requiring amputation (major: above ankle, minor: below ankle), categorized by level on the foot, ankle, or leg.
Trial Locations
- Locations (10)
Holy Name Medical Center
🇺🇸Teaneck, New Jersey, United States
Arkansas Heart Hospital
🇺🇸Little Rock, Arkansas, United States
Hattiesburg Clinic
🇺🇸Hattiesburg, Mississippi, United States
Denver Veterans Administration Hospital
🇺🇸Denver, Colorado, United States
Mid-Michigan Heart & Vascular
🇺🇸Saginaw, Michigan, United States
Sanford Research
🇺🇸Sioux Falls, South Dakota, United States
St.Louis University Hospital
🇺🇸Saint Louis, Missouri, United States
Tennova - Turkey Creek Medical Center
🇺🇸Knoxville, Tennessee, United States
Mission Research Institute (New Braunfels Cardiology - GRMC)
🇺🇸New Braunfels, Texas, United States
UNC Health Care - Rex Hospital
🇺🇸Raleigh, North Carolina, United States