The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular...
Transcript of The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular...
![Page 1: The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery University of California, San Francisco Section Chief, Vascular Surgery San](https://reader034.fdocuments.net/reader034/viewer/2022051815/603b82aa73d24252df0dcff1/html5/thumbnails/1.jpg)
The DANCE Trial
Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery
University of California, San Francisco Section Chief, Vascular Surgery San Francisco VA Medical Center
Associate Chief, Surgery San Francisco VA Medical Center Director, Vascular Integrated Physiology and Experimental
Therapeutics (VipeRx) Laboratory
1
![Page 2: The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery University of California, San Francisco Section Chief, Vascular Surgery San](https://reader034.fdocuments.net/reader034/viewer/2022051815/603b82aa73d24252df0dcff1/html5/thumbnails/2.jpg)
Disclosure
Speaker name: Christopher D. Owens, MD
.................................................................................
I have the following potential conflicts of interest to report:
Consulting
Employment in industry
Stockholder of a healthcare company
Owner of a healthcare company
Other(s)
I do not have any potential conflict of interest
![Page 3: The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery University of California, San Francisco Section Chief, Vascular Surgery San](https://reader034.fdocuments.net/reader034/viewer/2022051815/603b82aa73d24252df0dcff1/html5/thumbnails/3.jpg)
DANCE Trial Organization National Co-PIs Christopher Owens, MD, UCSF/SFVAMC
Mahmood Razavi, MD, St. Joseph’s, Orange, CA
Ultrasound Core Laboratory Vascore, Boston, MA Director: Michael Jaff, DO
Angiographic Core Laboratory CRF, New York, NY Director: Philippe Genereux, MD
Biomarker Laboratory Quest Diagnostics Clinical Trials
Sites: George Adams, MD – UNC Healthcare, Rex Hospital, Raleigh, NC Guarav Aggarwala, MD – Palestine Regional Medical, Palestine, TX Sam Ahn, MD – DFW Vascular Group, Dallas, TX Vaquar Ali – First Coast Cardiovascular Institute, Jacksonville, FL Gary Ansel, MD – OhioHealth - Riverside Methodist, Columbus, OH Ehrin Armstrong, MD – Denver VA, Denver, CO Nelson Bernardo – MedStar Washington Hospital Center, DC Ian Cawich, MD – Arkansas Heart Hospital, Little Rock, AR Michael Curi, MD – Rutgers Univ. Hospital – Newark, NJ Tom Davis, MD – St. John Providence Hospital, Detroit, MI Suhail Dohad, MD – Cardiovascular Research Foundation, Beverly Hills, CA
W. Britton Eaves, MD – Willis Knighton Medical Center, Bossier City, LA Andrey Espinoza, MD – Hunterdon Medical Center, Flemington, NJ Robert Feldman, MD – Munroe Regional Medical Center, Ocala, FL Stuart Harlan, MD – Coastal Vascular & Interventional Center, Pensacola, FL Donald Jacobs, MD – St. Louis University Hospital, St. Louis MO Richard Kovach, MD – Deborah Heart & Lung, Browns Mills, NJ Louis Lopez, MD – St. Joseph Hospital, Ft. Wayne, IN Amir Malik, MD – Plaza Med Ctr., Ft. Worth, TX Luke Marone, MD – UPMC, Pittsburgh, PA Christopher Metzger, MD – Wellmont Health, Kingsport, TN Christopher Owens, MD – UCSF / SFVAMC, San Francisco, CA John Pacanowski, MD – PIMA Vascular, Tucson, AZ Richard Powell – Dartmouth-Hitchcock Medical Center, Lebanon, NH
Anthony Pucillo, MD – Columbia Presbyterian, New York, NY Venkatesh Ramaiah, MD – Arizona Heart Hospital, Phoenix, AZ Mahmood Razavi, MD - St. Joseph Hospital of Orange Heart & Vascular Center, Orange, CA Bhavanada Reddy, MD – Alpine Research, Salt Lake City, UT Andrez Shanzer, MD – UMass Medical Ctr., Worcester, MA Immad Sadiq, MD – Hartford Hospital, Hartford CT Peter Soukas, MD – Miriam Hospital, Providence RI Cezar Staniloae, MD – Gotham Cardiovascular Research, New York, NY John Taggert, MD – Albany Vascular Group, Albany, NY Robert Wilkins, MD – Hattiesburg Clinic, Hattiesburg, MS John Winscott, MD – Univ of Mississippi Med Ctr., Jackson, MS Jason Yoho, MD – Mission Research - Guadalupe Regional, Seguin, TX 3
![Page 4: The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery University of California, San Francisco Section Chief, Vascular Surgery San](https://reader034.fdocuments.net/reader034/viewer/2022051815/603b82aa73d24252df0dcff1/html5/thumbnails/4.jpg)
DANCE: Dexamethasone delivered to the Adventitia to eNhance Clinical Efficacy
• Open label, single arm trial
• Primary endpoints:
– Efficacy: 12 month patency (duplex ultrasound PSVR≤2.4 and lack of CD-TLR)
– Safety: MALE through 12 months, POD through 30 days
• Key eligibility criteria:
– Rutherford 2-4
– SFA or popliteal
– De novo or restenotic lesions ≤15 cm length
– ≤30% residual stenosis after revascularization
4
![Page 5: The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery University of California, San Francisco Section Chief, Vascular Surgery San](https://reader034.fdocuments.net/reader034/viewer/2022051815/603b82aa73d24252df0dcff1/html5/thumbnails/5.jpg)
DANCE Trial Enrollment and Design
5
First 100 patients enrolled, 12 mo
interim data presented today
![Page 6: The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery University of California, San Francisco Section Chief, Vascular Surgery San](https://reader034.fdocuments.net/reader034/viewer/2022051815/603b82aa73d24252df0dcff1/html5/thumbnails/6.jpg)
First 100 DANCE-ATX Patients Enrolled (Interim Data)
100 Enrolled 01 Nov 2014
to 07 Jan 2015
12 Withdrawn or Lost to Follow-Up
3 Deaths prior to endpoint
73 Analyzed for Primary Patency and TLR Endpoints
6
12 Failed revascularization (per Core Lab analysis,
>33% angiographic stenosis at completion or not
patent at baseline ultrasound)
![Page 7: The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery University of California, San Francisco Section Chief, Vascular Surgery San](https://reader034.fdocuments.net/reader034/viewer/2022051815/603b82aa73d24252df0dcff1/html5/thumbnails/7.jpg)
The Bullfrog® Micro-Infusion Device (Mercator MedSystems)
7
20% contrast
80% dexamethasone
The Bullfrog Micro-Infusion Device is FDA 510(k)-cleared and CE-Marked
![Page 8: The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery University of California, San Francisco Section Chief, Vascular Surgery San](https://reader034.fdocuments.net/reader034/viewer/2022051815/603b82aa73d24252df0dcff1/html5/thumbnails/8.jpg)
Interrupting the Cascade at Inflammation
8
ATVB 2011;31:1530-
1539
Cell recruitment
Inflammation –
cytokine expression Proliferation
Neointima
Lumen Loss
![Page 9: The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery University of California, San Francisco Section Chief, Vascular Surgery San](https://reader034.fdocuments.net/reader034/viewer/2022051815/603b82aa73d24252df0dcff1/html5/thumbnails/9.jpg)
DANCE Demographics
N 73
Age 68.9 ± 10.5
Male 52.1%
Caucasian 78.1%
African American 20.5%
Diabetes 43.1%
Coronary artery disease 66.7%
Hypertension 93.1%
Hyperlipidemia 76.4%
BMI (kg/m2) 31.6 ± 18.1
Creatinine (mg/dL) 1.04 ± 0.35
hsCRP, baseline (mg/dL) 5.2 ± 5.4
9
![Page 10: The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery University of California, San Francisco Section Chief, Vascular Surgery San](https://reader034.fdocuments.net/reader034/viewer/2022051815/603b82aa73d24252df0dcff1/html5/thumbnails/10.jpg)
DANCE Vascular Disease and Lesion Characteristics
Rutherford 2 23.3%
Rutherford 3 61.6%
Rutherford 4 15.1%
Severe Calcification 26.6%
Popliteal Involvement 20.5%
TASC II Classification 36% A; 59% B; 6% C
Restenosis 8.2%
Lesion Length (cm) 8.8 ± 5.2
Diameter Stenosis Pre-Revascularization 69% ± 17%
Total Occlusions 15.4%
Grade B-D Dissection 25.0%
Stent Utilization 34.2%
Residual Stenosis Post-Revascularization 20% ± 7% 10
![Page 11: The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery University of California, San Francisco Section Chief, Vascular Surgery San](https://reader034.fdocuments.net/reader034/viewer/2022051815/603b82aa73d24252df0dcff1/html5/thumbnails/11.jpg)
DANCE Safety and Efficacy Endpoints
11
SAFETY
Device-related SAE 0-360 Days 0/83 (0%)
Drug-related SAE 0-360 Days 0/83 (0%)
Major Adverse Limb Events 0-360 Days Amputation Bypass Thrombolysis
0/83 (0%)
2/83 (2.4%) 0/83 (0%)
Death 0-30 Days 0/97 (0%)
Death 0-360 Days 5/88 (5.7%)
EFFICACY
TLR at 360 Days 8.3%
Patency at 360 Days 85.0%
TLR at 390 Days 8.8%
Patency at 390 Days 81.5%
![Page 12: The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery University of California, San Francisco Section Chief, Vascular Surgery San](https://reader034.fdocuments.net/reader034/viewer/2022051815/603b82aa73d24252df0dcff1/html5/thumbnails/12.jpg)
Putting DANCE into Perspective versus Published Drug Delivery
12
85% 78% 82%
52% 65%
53%
0%
20%
40%
60%
80%
100%
DANCE(Atherectomy +
Bullfrog/Dex)
DEFINITIVE-LE(Atherectomy)
In.Pact SFA(PTX DCB)
In.Pact SFA(PTA)
Levant 2(PTX DCB)
Levant 2(PTA)
12 Month Patency
Lesion Length 8.8 cm 7.5 cm 8.9 cm 8.8 cm 6.3 cm 6.3 cm
Ruth 4 % 15.1% 0% 5.0% 5.4% 7.9% 8.1%
TASCII A:B:C % 36:59:6 57:31:12 63:27:11 76:22:2 76:24:1
Popliteal % 20.5% 15.3% 6.8% 7.1% 9.8% 7.5%
Severe Ca2+ % 26.6% 8.1% 6.2% 10.4% 8.1%
![Page 13: The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery University of California, San Francisco Section Chief, Vascular Surgery San](https://reader034.fdocuments.net/reader034/viewer/2022051815/603b82aa73d24252df0dcff1/html5/thumbnails/13.jpg)
DANCE Clinical Endpoints
13
* Statistically significant (P<0.05) improvement versus baseline screening exam
0
1
2
3
4
Screening 4wk 6mo 12mo
Rutherford Classification
*
* *
0
10
20
30
40
50
60
70
80
90
100
Screening 4 wk 6 mo 12 mo
Walking Impairment Questionnaire Scores
* * *
![Page 14: The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery University of California, San Francisco Section Chief, Vascular Surgery San](https://reader034.fdocuments.net/reader034/viewer/2022051815/603b82aa73d24252df0dcff1/html5/thumbnails/14.jpg)
Novel DANCE Endpoints - Biomarkers
14
• Circulating levels rise in
response to local triggers (e.g.
inflammation)
• Primitive antibody
• Elevations tied to restenosis
[Schillinger et al. Radiology
2002; 225:21-26.]
C-Reactive Protein (CRP)
• Recruits inflammatory cells to the
site of injury
• Elevations tied to restenosis
[Cipollone F, et al. Arterioscler
Thromb Vasc Biol 2001;21:327-
334.]
Monocyte Chemoattractive
Protein-1 (MCP-1)
![Page 15: The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery University of California, San Francisco Section Chief, Vascular Surgery San](https://reader034.fdocuments.net/reader034/viewer/2022051815/603b82aa73d24252df0dcff1/html5/thumbnails/15.jpg)
Inflammatory Biomarker Reductions
-50%
-40%
-30%
-20%
-10%
0%
10%
20%
30%
% Change from Baseline to 24 hours
Normalized MCP-1 Change in Median from
Baseline to 24 Hours After Interventions
Non-Dex Comparator (PTA or Stenting of SFA;Heider, JVS 2006;43:969, N=32)
Dex Treatment (DANCE Atherectomy, N=39)15
0%
50%
100%
150%
200%
250%
300%
350%
400%
% Change from Baseline to 24 hours
Normalized CRP Change in Median from Baseline
to 24 Hours After Interventions
Non-Dex Control (DANCE-PartnerAtherectomy, N=7)
Dex Treatment (DANCE Atherectomy, N=42)
![Page 16: The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery University of California, San Francisco Section Chief, Vascular Surgery San](https://reader034.fdocuments.net/reader034/viewer/2022051815/603b82aa73d24252df0dcff1/html5/thumbnails/16.jpg)
Summary
• Bullfrog delivery of GR-agonist (dexamethasone) after atherectomy reduces production of pro-inflammatory cytokines and acute phase reactants versus atherectomy alone
• The first 73 eligible patients reaching their endpoint in the atherectomy group of DANCE have demonstrated strong patency results, with 85% remaining patent at 360 days and 81.5% remaining patent at 390 days
• The DANCE trial enrolled a challenging cohort with a high representation of Rutherford 4 (15%), severe calcification (27%), popliteal involvement (21%), and TASCII B lesions (59%)
• The early results of GR-agonist micro-infusion in peripheral arteries at the time of atherectomy appears promising, particularly given the inherent safety profile of currently approved steroids
16
![Page 17: The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery University of California, San Francisco Section Chief, Vascular Surgery San](https://reader034.fdocuments.net/reader034/viewer/2022051815/603b82aa73d24252df0dcff1/html5/thumbnails/17.jpg)
Conclusions
• The DANCE trial is a proof-of-principle study which supports a paradigm shift in anti-restenosis therapy away from intimal delivery platforms
• Adventitial delivery of powerful GR-agonist therapy results in the nuclear immunomodulation of the vascular injury response to reduce restenosis while permitting the unimpeded re-establishment of vascular endothelium
17
![Page 18: The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery University of California, San Francisco Section Chief, Vascular Surgery San](https://reader034.fdocuments.net/reader034/viewer/2022051815/603b82aa73d24252df0dcff1/html5/thumbnails/18.jpg)
Next Phase: LIMBO Trials
• Below-Knee
• 2 trials: Adventitial
Dexamethasone added to
PTA (Germany) or
atherectomy (U.S.)
• Anticipated start: Q1 2016
• LIMBO-PTA PI: Dierk
Scheinert, MD, University
Hospital Leipzig, Germany
• LIMBO-ATX coPIs: George
Adams, MD, UNC-Rex,
Raleigh, NC
Don Jacobs, MD, St. Louis
University, MO
60 controls
Baseline angiogram and biomarker blood draw
24-hour blood draw for biomarkers
Clinical, hemodynamic and angiographic follow-up at 6 months
1-month blood draw for biomarkers
LIMBO-PTA
120 ATX (U.S.) 120 PTA (Germany)
60 DEX 60 controls 60 DEX
LIMBO-ATX
![Page 19: The DANCE Trial · Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery University of California, San Francisco Section Chief, Vascular Surgery San](https://reader034.fdocuments.net/reader034/viewer/2022051815/603b82aa73d24252df0dcff1/html5/thumbnails/19.jpg)
The DANCE Trial
Christopher D. Owens, MD, MSc Associate Professor of Vascular and Endovascular Surgery
University of California, San Francisco Section Chief, Vascular Surgery San Francisco VA Medical Center
Associate Chief, Surgery San Francisco VA Medical Center Director, Vascular Integrated Physiology and Experimental
Therapeutics (VipeRx) Laboratory
19