Clinical trial NCT01983449: Effectiveness of Adventitial Dexamethasone in Peripheral Artery Disease
Official title: Delivery of Dexamethasone to the Adventitia to eNhance Clinical Efficacy After Femoropopliteal Revascularization
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Peripheral Arterial Diseases
Keywords: Adventitia
Peripheral Artery Disease
Restenosis
Inflammation
Anti-Inflammatory
Dexamethasone
Lead sponsor: Mercator MedSystems, Inc.
Sponsor class: INDUSTRY
First posted: 2013-11-14
Enrollment: 285
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To assess the safety and effectiveness of adventitial deposition of the Study Drug in reducing inflammation and restenosis in patients with clinical evidence of claudication or critical limb ischemia and an angiographically significant lesion in the superficial femoral and/or popliteal arteries.

Study Drug and Dose: Dexamethasone Sodium Phosphate Injection, USP, 4 mg/ml, with dilute contrast (17%) administered to the adventitia in a dose of 1.6 mg per cm of desired vessel treatment length.

Detailed description: This trial will examine the ability for adventitial dexamethasone to safely delay restenosis in patients at least 18 years of age, who have peripheral atherosclerotic lesions involving the superficial femoral and/or popliteal arteries. These patients have no current therapeutic alternatives beyond the procedure used to open, or revascularize, their superficial femoral and/or popliteal arteries. Metal stents have the potential to fracture when implanted in this artery segment due to continual flexion and bending of the knee. It is desirable to improve the patency of this artery after percutaneous transluminal angioplasty (PTA) and/or atherectomy-based revascularization.

Eligibility criteria: Inclusion Criteria:

* Screening Criteria

  * Male or non-pregnant female ≥18 years of age
  * Rutherford Clinical Category 2-4
  * Clinical diagnosis of PAD requiring revascularization, secondary to atherosclerosis affecting a lower limb
  * Patient is willing to provide informed consent and comply with the required follow up visits, testing schedule, and medication regimen
* Procedural Criteria

  * De novo or nonstented restenotic lesions \>90 days from prior angioplasty and/or atherectomy, at least 3 cm from any previously placed stent or vascular surgery site
  * \>70% diameter stenosis up to 15 cm in total length (with no greater than 3 cm length of contiguous intervening normal artery) in the superficial femoral and/or popliteal artery (between the profunda and tibioperoneal trunk)
  * Reference vessel diameter ≥3mm and ≤ 8mm
  * Successful wire crossing of lesion
  * A patent artery proximal to the index lesion free from significant stenosis (significant stenosis is defined as \>50% in iliac or \>30% stenosis in common femoral artery) as confirmed by angiography (treatment of target lesion after successful treatment of iliac or common femoral artery lesions is acceptable)

Exclusion Criteria:

* Screening Criteria

  * Pregnant, nursing or planning on becoming pregnant in \< 2 years
  * Life expectancy of \<2 years
  * Known active malignancy
  * History of solid organ transplantation
  * Patient actively participating in another investigational device or drug study
  * History of hemorrhagic stroke within 3 months
  * Previous or planned surgical or interventional procedure within 30 days of index procedure
  * Chronic renal insufficiency with eGFR \<29
  * Prior bypass surgery, stenting of the target lesion
  * Inability to take required study medications
  * Contra-indication or known hypersensitivity to dexamethasone sodium phosphate, contrast media, or Physician prescribed antiplatelet regimen as indicated
  * Systemic fungal infection
  * Anticipated use of IIb/IIIa inhibitor prior to index lesion treatment
  * Acute or sub-acute thrombus, acute vessel occlusion or sudden symptom onset
  * Acute limb ischemia
  * Prior participation of the index limb in the current study (contralateral treatment is allowed)
  * Inability to ambulate (e.g. from prior ipsilateral or contralateral amputation)
  * Patient is receiving steroids already, however locally acting inhaled steroids for asthma treatment do not exclude patients from the trial
* Procedural Criteria

  * Lesions extending into the trifurcation or above the profunda
  * Heavy eccentric or moderate circumferential calcification at index lesion, which in the judgment of the investigator would prevent penetration of the Micro-Infusion Catheter needle through the vessel wall
  * Lesion length is \>15 cm as measured from proximal normal vessel to distal normal vessel, or there is no normal proximal arterial segment in which duplex ultrasound velocity ratios can be measured
  * Inadequate distal outflow defined as absence of at least one patent tibial artery (no lesion \>50% stenosis) with flow into the foot
  * Use of adjunctive therapies other than angioplasty, atherectomy (mechanical or laser) or bare metal stenting (i.e. scoring/cutting balloon, drug-eluting stent, drug-coated balloon, cryoplasty, etc.)

Primary outcomes:
measure: MALE-POD
timeFrame: 30 days
measure: Duplex ultrasound index lesion binary restenosis
timeFrame: 6 months
measure: Duplex ultrasound index lesion binary restenosis
timeFrame: 12 months
Secondary outcomes:
measure: Long term safety
timeFrame: 30 days to 6 months
measure: Duplex ultrasound index lesion flow limiting restenosis
timeFrame: 6 and 12 months
measure: Change in inflammatory biomarkers
timeFrame: Baseline and 24 hours
measure: Vascular patency
timeFrame: 6, 12, 18 and 24 months
measure: Clinical outcome measures
timeFrame: 1, 6, 12, 18 and 24 months
measure: Infusion Technical Success
timeFrame: Intraprocedural
measure: Procedural Success
timeFrame: Intraprocedural
measure: Healthcare Economics
timeFrame: 30 days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Heart Hospital / Abrazo Health Care Research / Tenet Health
state: Arizona
city: Tucson
country: United States
facility: Pima Vascular
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Heart Hospital
state: Arkansas
city: Beverly Hills
country: United States
facility: Cardiovascular Medical Group of Southern California / Cardiovascular Research Foundation
state: California
city: Orange
country: United States
facility: St. Joseph Hospital of Orange Heart and Vascular Center
state: California
city: San Francisco
country: United States
facility: San Francisco VA Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Denver
country: United States
facility: VA Eastern Colorado Healthcare System
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Washington
country: United States
facility: MedStar Health Washington Hospital Center
state: District of Columbia
city: Jacksonville
country: United States
facility: First Coast Cardiovascular Institute
state: Florida
city: Ocala
country: United States
facility: Munroe Regional Medical Center
state: Florida
city: Pensacola
country: United States
facility: Coastal Vascular & Interventional
state: Florida
city: Fort Wayne
country: United States
facility: St. Joseph Hospital
state: Indiana
city: Shreveport
country: United States
facility: Willis-Knighton Medical Center
state: Louisiana
city: Worcester
country: United States
facility: UMass Medical School
state: Massachusetts
city: Detroit
country: United States
facility: St. John Providence Hospital and Medical Center
state: Michigan
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic
state: Mississippi
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: St.Louis University Hospital
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Browns Mills
country: United States
facility: Deborah Heart & Lung Center
state: New Jersey
city: Flemington
country: United States
facility: Hunterdon Medical Center
state: New Jersey
city: Newark
country: United States
facility: Rutgers New Jersey Medical School
state: New Jersey
city: Albany
country: United States
facility: Albany Vascular Group
state: New York
city: New York
country: United States
facility: Gotham Cardiovascular Research / New York Cardiovascular Associates
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Raleigh
country: United States
facility: UNC Health Care - Rex Hospital
state: North Carolina
city: Columbus
country: United States
facility: OhioHealth
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Heart & Vascular Institute
state: Pennsylvania
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Kingsport
country: United States
facility: Wellmont CVA Heart Institute
state: Tennessee
city: Dallas
country: United States
facility: DFW Vascular Group
state: Texas
city: Fort Worth
country: United States
facility: Plaza Medical Center at Fort Worth
state: Texas
city: Palestine
country: United States
facility: Palestine Regional Medical Center
state: Texas
city: Seguin
country: United States
facility: Mission Research Institute (Guadalupe Regional Medical Center)
state: Texas
city: Salt Lake City
country: United States
facility: Alpine Research / Utah Cardiology
state: Utah
city: Seattle
country: United States
facility: University of Washington Veterans Center
state: Washington
Study officials:
affiliation: St. Joseph's Vascular Institute
name: Mahmood Razavi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Razavi MK, Donohoe D, D'Agostino RB Jr, Jaff MR, Adams G; DANCE Investigators. Adventitial Drug Delivery of Dexamethasone to Improve Primary Patency in the Treatment of Superficial Femoral and Popliteal Artery Disease: 12-Month Results From the DANCE Clinical Trial. JACC Cardiovasc Interv. 2018 May 28;11(10):921-931. doi: 10.1016/j.jcin.2017.12.015. Epub 2018 May 2.