Lower-Limb Adventitial Infusion of DexaMethasone Via Bullfrog to Reduce Occurrence of Restenosis After Atherectomy (ATX)-Based Revascularization

NCT02479620 | Unknown Phase 2 DMC

• 1 other identifier: CIP0173
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 10

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).

Conditions

Chronic Limb Ischemia

Outcome Measures

Primary Outcomes (4)

• 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 (19)

• Composite clinical safety by freedom from adverse events including death, unplanned amputation, CD-TLR, SAE or MALE.

  Up to 12 months following the procedure

• Event-free survival

  12 months following the procedure

• QVA change from post-procedure

  6 months following the procedure

• IVUS change from post-procedure

  6 months following the procedure

• Amputation-free survival

  30 days, 6 and 12 months following the procedure

Study Arms (2)

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

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.

Dexamethasone Delivery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• Screening Criteria:
• Patient unwilling or unlikely to comply with visit schedule
• Planned major index limb amputation
• 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

Sponsors & Collaborators

• Mercator MedSystems, Inc.: lead

Study Sites (10)

Arkansas Heart Hospital

Little Rock, Arkansas, 72211, United States

Location

Denver Veterans Administration Hospital

Denver, Colorado, 80220, United States

Location

Mid-Michigan Heart & Vascular

Saginaw, Michigan, 48604, United States

Location

Hattiesburg Clinic

Hattiesburg, Mississippi, 39401, United States

Location

St.Louis University Hospital

St Louis, Missouri, 63110, United States

Location

Holy Name Medical Center

Teaneck, New Jersey, 07666, United States

Location

UNC Health Care - Rex Hospital

Raleigh, North Carolina, 27607, United States

Location

Sanford Research

Sioux Falls, South Dakota, 57101, United States

Location

Tennova - Turkey Creek Medical Center

Knoxville, Tennessee, 37934, United States

Location

Mission Research Institute (New Braunfels Cardiology - GRMC)

New Braunfels, Texas, 78130, United States

Location

MeSH Terms

Interventions

dexamethasone 21-phosphate

Study Officials

• George Adams, MD

  REX Hospital, University of North Carolina Healthcare

  PRINCIPAL INVESTIGATOR

• Donald Jacobs, MD

  Saint Louis University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2015
• First Posted: June 24, 2015
• Study Start: June 1, 2016
• Primary Completion: November 1, 2019
• Study Completion: March 1, 2020
• Last Updated: February 19, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share

Locations

US (10)