Lower-Limb Adventitial Infusion of DexaMethasone Via Bull... | NCT02479555

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Treatment Group: Dexamethasone Delivery	Active Comparator	Up to 60 angioplasty procedures at up to 30 sites in Europe and in the United States. Patients will be randomized 1:1 to receive either the active treatment or control therapy. Treatment Group: Standard endovascular revascularization therapy consisting of angioplasty followed by Dexamethasondihydrogenphosphat-dinatrium (Ph.Eur.) 4 mg/mL Injektionslösung and with or without stent placement. The drug is diluted to 3.2 mg/mL and administered to the adventitia per Bullfrog Instructions for Use in a dose of 0.8 mg dexamethasone (0.25 mL) per cm of desired vessel treatment length, up to 30 cm.	Drug: Dexamethasone sodium phosphate injection, USP, 4 mg/mL
Control Group	No Intervention	Up to 60 angioplasty procedures at up to 30 sites in Europe and in the United States. Patients will be randomized 1:1 to receive either the active treatment or control therapy. Control Group: Standard endovascular revascularization therapy consisting of angioplasty with or without stent placement. No specific distribution of gender regarding enrollment or randomization is intended. There will also be a separate randomization of patients with Rutherford 6 score to a maximum of 20 enrolled patients.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Dexamethasone sodium phosphate injection, USP, 4 mg/mL	Drug	Post-balloon angioplasty revascularization, the unblinded Pharmacist will prepare a sterile 20 mL syringe (Luer locking) with 16 mL of investigational drug or placebo per assignment. The unblinded Pharmacist provides syringe to investigator. Syringe shall only be labeled with the study number, patient number, randomization number and "Investigational Drug". "Investigational Drug" will be administered via Bullfrog Micro-Infusion Device.

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 a failure to successfully treat and obtain a <30% residual stenosis
Index lesion length is >30 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-index lesions) >50 cm
Lesions revascularized during the index case but untreated by Bullfrog
Use of alternative therapy, e.g. atherectomy, laser, or 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