DANCE: Effectiveness of Adventitial Dexamethasone in Peripheral Artery Disease

Sponsor

Mercator MedSystems, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01983449

Collaborator

(none)

285

Enrollment

Locations

Arm

Duration (Months)

7.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Peripheral Arterial Diseases	Drug: Dexamethasone Sodium Phosphate Injection, USP	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

285 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2013

Actual Primary Completion Date :

Dec 1, 2016

Actual Study Completion Date :

Jan 1, 2018

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

MALE-POD [30 days]
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.
Duplex ultrasound index lesion binary restenosis [6 months]
Binary restenosis will be judged by core laboratory interpretation with peak systolic velocity ratio (PSVR) greater than 2.4.
Duplex ultrasound index lesion binary restenosis [12 months]
Binary restenosis will be judged by core laboratory interpretation with peak systolic velocity ratio (PSVR) greater than 2.4.

Secondary Outcome Measures

Long term safety [30 days to 6 months]
Long term safety outcomes that occur after 30 days through 6 months post-procedure will be determined by evaluating adverse events.
Duplex ultrasound index lesion flow limiting restenosis [6 and 12 months]
Flow limiting restenosis will be judged by core laboratory as PSVR>4.0.
Change in inflammatory biomarkers [Baseline and 24 hours]
Change in inflammatory biomarkers will be measured with a panel of biomarkers in 1/3 of patients.
Vascular patency [6, 12, 18 and 24 months]
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.
Clinical outcome measures [1, 6, 12, 18 and 24 months]
Modified Walking Impairment Questionnaire, Ankle-Brachial Index, Rutherford Score.
Infusion Technical Success [Intraprocedural]
Distribution grade around infusion sites.
Procedural Success [Intraprocedural]
Establishment of antegrade flow with residual stenosis of <30% by angiogram.
Healthcare Economics [30 days]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Heart Hospital / Abrazo Health Care Research / Tenet Health	Phoenix	Arizona	United States	85016
2	Pima Vascular	Tucson	Arizona	United States	85718
3	Arkansas Heart Hospital	Little Rock	Arkansas	United States	72211
4	Cardiovascular Medical Group of Southern California / Cardiovascular Research Foundation	Beverly Hills	California	United States	90210
5	St. Joseph Hospital of Orange Heart and Vascular Center	Orange	California	United States	92868
6	San Francisco VA Medical Center	San Francisco	California	United States	94121
7	University of California San Francisco Medical Center	San Francisco	California	United States	94131
8	VA Eastern Colorado Healthcare System	Denver	Colorado	United States	80220
9	Hartford Hospital	Hartford	Connecticut	United States	06702
10	MedStar Health Washington Hospital Center	Washington	District of Columbia	United States	20010
11	First Coast Cardiovascular Institute	Jacksonville	Florida	United States	32216
12	Munroe Regional Medical Center	Ocala	Florida	United States	34471
13	Coastal Vascular & Interventional	Pensacola	Florida	United States	32504
14	St. Joseph Hospital	Fort Wayne	Indiana	United States	46802
15	Willis-Knighton Medical Center	Shreveport	Louisiana	United States	71103
16	UMass Medical School	Worcester	Massachusetts	United States	01655
17	St. John Providence Hospital and Medical Center	Detroit	Michigan	United States	48326
18	Hattiesburg Clinic	Hattiesburg	Mississippi	United States	39401
19	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
20	St.Louis University Hospital	Saint Louis	Missouri	United States	63110
21	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03766
22	Deborah Heart & Lung Center	Browns Mills	New Jersey	United States	08015
23	Hunterdon Medical Center	Flemington	New Jersey	United States	08822
24	Rutgers New Jersey Medical School	Newark	New Jersey	United States	07103
25	Albany Vascular Group	Albany	New York	United States	12208
26	Gotham Cardiovascular Research / New York Cardiovascular Associates	New York	New York	United States	10001
27	Columbia University Medical Center	New York	New York	United States	10032
28	UNC Health Care - Rex Hospital	Raleigh	North Carolina	United States	27607
29	OhioHealth	Columbus	Ohio	United States	43214
30	UPMC Heart & Vascular Institute	Pittsburgh	Pennsylvania	United States	15232
31	The Miriam Hospital	Providence	Rhode Island	United States	02906
32	Wellmont CVA Heart Institute	Kingsport	Tennessee	United States	37660
33	DFW Vascular Group	Dallas	Texas	United States	75208
34	Plaza Medical Center at Fort Worth	Fort Worth	Texas	United States	76104
35	Palestine Regional Medical Center	Palestine	Texas	United States	75801
36	Mission Research Institute (Guadalupe Regional Medical Center)	Seguin	Texas	United States	78155
37	Alpine Research / Utah Cardiology	Salt Lake City	Utah	United States	84041
38	University of Washington Veterans Center	Seattle	Washington	United States	98195