Lower-Limb Adventitial Infusion of DexaMethasone Via Bull... | NCT02479620

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Dexamethasone Delivery	Active Comparator	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.	Drug: Dexamethasone Sodium Phosphate Injection, USP, 4 mg/mL
Control	No Intervention	Up to 60 atherectomy-based revascularization procedures at up to 30 sites in the United States and Europe. Standard endovascular revascularization therapy consisting of atherectomy with or without angioplasty and with or without stent placement. No additional drug will be given to Subjects randomized to Control.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Dexamethasone Sodium Phosphate Injection, USP, 4 mg/mL	Drug	Following atherecomy-based revascularization, Investigators will be unblinded to assignment and will treat only patients assigned to the treatment arm with the Bullfrog delivery of dexamethasone.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Freedom from MALE	Freedom from major adverse limb event (MALE) within 6 months.	Up to 6 Months following the procedure
Freedom from CD-TLR	Freedom from clinically driven target lesion revascularization (CD-TLR) within 6 months.	Up to 6 Months following the procedure
Composite clinical safety by freedom from adverse events including death, MALE, major unplanned amputation, or CD-TLR.	Freedom from composite of death within 30 days from the index procedure, MALE, major unplanned amputation or CD-TLR within 6 months.	Up to 6 Months following the procedure
TVAL% change from post-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	6 Months following the procedure

Secondary Outcomes

Measure	Description	Time Frame
Composite clinical safety by freedom from adverse events including death, unplanned amputation, CD-TLR, SAE or MALE.	Freedom from composite of death, unplanned amputation and CD-TLR, serious adverse events (SAE) and MALE.	Up to 12 months following the procedure
Event-free survival

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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)

Exclusion Criteria:

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

Name	Affiliation	Role
George Adams, MD	REX Hospital, University of North Carolina Healthcare	Principal Investigator
Donald Jacobs, MD	Saint Louis University Hospital	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Arkansas Heart Hospital		Little Rock	Arkansas	72211	United States
Denver Veterans Administration Hospital