Effectiveness of Adventitial Dexamethasone in Peripheral Artery Disease (DANCE)

Delivery of Dexamethasone to the Adventitia to eNhance Clinical Efficacy After Femoropopliteal Revascularization

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.

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Diseases
• Intervention / Treatment: Drug: Dexamethasone Sodium Phosphate Injection, USP

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.

• Study Type: Interventional
• Enrollment (Actual): 285
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Arizona Heart Hospital / Abrazo Health Care Research / Tenet Health
    • Tucson, Arizona, United States, 85718
      • Pima Vascular
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Arkansas Heart Hospital
  • California
    • Beverly Hills, California, United States, 90210
      • Cardiovascular Medical Group of Southern California / Cardiovascular Research Foundation
    • Orange, California, United States, 92868
      • St. Joseph Hospital of Orange Heart and Vascular Center
    • San Francisco, California, United States, 94121
      • San Francisco VA Medical Center
    • San Francisco, California, United States, 94131
      • University of California San Francisco Medical Center
  • Colorado
    • Denver, Colorado, United States, 80220
      • VA Eastern Colorado Healthcare System
  • Connecticut
    • Hartford, Connecticut, United States, 06702
      • Hartford Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Health Washington Hospital Center
  • Florida
    • Jacksonville, Florida, United States, 32216
      • First Coast Cardiovascular Institute
    • Ocala, Florida, United States, 34471
      • Munroe Regional Medical Center
    • Pensacola, Florida, United States, 32504
      • Coastal Vascular & Interventional
  • Indiana
    • Fort Wayne, Indiana, United States, 46802
      • St. Joseph Hospital
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • Willis-Knighton Medical Center
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • UMass Medical School
  • Michigan
    • Detroit, Michigan, United States, 48326
      • St. John Providence Hospital and Medical Center
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Hattiesburg Clinic
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • St.Louis University Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Browns Mills, New Jersey, United States, 08015
      • Deborah Heart & Lung Center
    • Flemington, New Jersey, United States, 08822
      • Hunterdon Medical Center
    • Newark, New Jersey, United States, 07103
      • Rutgers New Jersey Medical School
  • New York
    • Albany, New York, United States, 12208
      • Albany Vascular Group
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10001
      • Gotham Cardiovascular Research / New York Cardiovascular Associates
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • UNC Health Care - Rex Hospital
  • Ohio
    • Columbus, Ohio, United States, 43214
      • OhioHealth
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Heart & Vascular Institute
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Wellmont CVA Heart Institute
  • Texas
    • Dallas, Texas, United States, 75208
      • DFW Vascular Group
    • Fort Worth, Texas, United States, 76104
      • Plaza Medical Center at Fort Worth
    • Palestine, Texas, United States, 75801
      • Palestine Regional Medical Center
    • Seguin, Texas, United States, 78155
      • Mission Research Institute (Guadalupe Regional Medical Center)
  • Utah
    • Salt Lake City, Utah, United States, 84041
      • Alpine Research / Utah Cardiology
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Veterans Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adventitial Dexamethasone; In patients receiving either angioplasty or atherectomy-based revascularization (pre-stratified to each by 50% of the total study), dexamethasone will be delivered to the adventitia following revascularization.	Drug: Dexamethasone Sodium Phosphate Injection, USP; Adventitial infusion of dexamethasone after angioplasty or atherectomy-based revascularization of the superficial femoral or popliteal artery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MALE-POD	Acute safety safety outcomes will be determined by evaluating the type, frequency, severity, and relatedness of Major Adverse Limb Events or Peri-Operative Death (MALE+POD) within 30 days from the procedure for all subjects.	30 days
Duplex ultrasound index lesion binary restenosis	Binary restenosis will be judged by core laboratory interpretation with peak systolic velocity ratio (PSVR) greater than 2.4.	6 months
Duplex ultrasound index lesion binary restenosis	Binary restenosis will be judged by core laboratory interpretation with peak systolic velocity ratio (PSVR) greater than 2.4.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long term safety	Long term safety outcomes that occur after 30 days through 6 months post-procedure will be determined by evaluating adverse events.	30 days to 6 months
Duplex ultrasound index lesion flow limiting restenosis	Flow limiting restenosis will be judged by core laboratory as PSVR>4.0.	6 and 12 months
Change in inflammatory biomarkers	Change in inflammatory biomarkers will be measured with a panel of biomarkers in 1/3 of patients.	Baseline and 24 hours
Vascular patency	Target lesion revascularization (TLR) rate, target extremity revascularization (TER) rate, limb salvage rate and primary patency (PSVR≤2.4 and no TLR) at 6, 12, 18 and 24 months. Note: provisional stenting performed during the index procedure shall not be considered to be TLR, TER or loss of primary patency.	6, 12, 18 and 24 months
Clinical outcome measures	Modified Walking Impairment Questionnaire, Ankle-Brachial Index, Rutherford Score.	1, 6, 12, 18 and 24 months
Infusion Technical Success	Distribution grade around infusion sites.	Intraprocedural
Procedural Success	Establishment of antegrade flow with residual stenosis of <30% by angiogram.	Intraprocedural
Healthcare Economics	Number of return visits and hospitalizations, time from index procedure to required revascularization and number of index-lesion-related readmissions within 30 days will be measured.	30 days

Collaborators and Investigators

• Sponsor: Mercator MedSystems, Inc.
• Investigators: Principal Investigator: Mahmood Razavi, MD, St. Joseph's Vascular Institute

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: November 4, 2013
• First Submitted That Met QC Criteria: November 7, 2013
• First Posted (Estimate): November 14, 2013

Study Record Updates

• Last Update Posted (Actual): March 8, 2018
• Last Update Submitted That Met QC Criteria: March 6, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Inflammation; Peripheral Artery Disease; Dexamethasone; Anti-Inflammatory; Restenosis; Adventitia
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101; Dexamethasone 21-phosphate
• Other Study ID Numbers: TSP0149; 1142183 (Other Identifier: Western IRB)