OMNIA case results: Lumee Oxygen measurements representative for CLI wound healing prognosis M Werner 1 Feb 2018
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Lumee Oxygen Platform is designed to provide immediate feedback on the quality of revascularization along the entire course of the patient s recovery OMNIA is a study designed to understand the relationship between revascularization success, traditional measures of gross hemodynamic characterization and Lumee measurement of tissue perfusion
How does LUMEE work? Excitation light from surface reader reaches hydrogel in tissue. Fluorescence chemistry on hydrogel responds based on oxygen concentration The fluorescent signal from hydrogel is captured by the reader. Data sent to cloud.
OMNIA - Oxygen Monitoring Near Ischemic Areas A prospective, single-arm, open-label, multicenter study Four Lumee sensors injected with 3 in the foot, and 1 reference sensor in the arm Lumee measurements performed continuously during endovascular revascularization procedures Lumee measurements also performed during functional assessment tests performed before and after revascularization, and at follow ups Traditional clinical metrics sampled throughout visit schedule include: arterial duplex, toe and ankle brachial index, WIFI scores, wound characterization and photographs Consent, Enrollment Sensor Injection Revascularization 1-29 days Functional Assessment Pre-operative Discharge 1 month 3 months 6 months
OMNIA: enrollment and safety A total of 3 study sites are actively enrolling: Prof. M. Brodmann, Med University of Graz / Austria Drs. T. Bisdas, A. Schwindt, St. Franziskus Hospital Münster / Germany Dr. M. Werner, Hanusch Hospital Vienna, Austria 21 subjects have been enrolled through end of 2017 21/21 were Rutherford Class 5 upon enrollment 19/21 received endovascular treatment 2/21 had bypass surgery after endo attempt 50 adverse events have been reported 27 are SAEs, all unrelated to study device 23 are AEs, 1 possibly related to study device (swelling described as mild and resolved at follow-up) 6
LOI [-] What information do we extract from Lumee Intra-Surgically? Reperfusion Modulation Defined as difference in LOI between baseline and maximum after intervention Baseline Therapeutic interventions Maximum during/after interventions Larger values are associated with greater increases in tissue oxygen during the procedure Reperfusion Modulation (Unitless) Data can be averaged across all Lumees, or selected from a Lumee of interest
What information do we extract from Lumee Post-Surgically? Recovery Modulation Baseline Leg Lift Defined as maximal change in LOI over a 5 minute window after the end of leg lift. It is expressed as a percentage of the baseline LOI before provocation Designed to capture the ability of vasculature to autoregulate following a leg lift (e.g. hyperemia) Larger values (above 100%) may represent extended hyperemia associated with poor vascular function Recovery Modulation = (1.7/2.2) = 77%
Provocation-response data at 1 month may provide metric of microvascular function Response from subject that healed Response from subject that failed Hypothesis: ability of vessels to regulate blood flow after ischemic challenge may be an indicator of vascular health 9
Tissue oxygen index Case report OMNIA trial Sex M Age (yrs) 65 Diabetes Type 2 Foot Side Right Rutherford Class 5 Wound Right second toe Therapy 1. Treated popliteal during this time via 1 set of balloon inflate/deflate 2. Treated anterior tibial during this time via 5 sets of balloon inflate/deflate 3. Use DCB (Lutonix 2.0/80mm) at anterior tibial and DP, 1 set of balloon inflate/deflate (1) (2) (3)
Lumee is responsive to the interventions delivered during revascularization Treated popliteal during this time via 1 set of balloon inflate/deflate Treated anterior tibial during this time via 5 sets of balloon inflate/deflate Use DCB (Lutonix 2.0/80mm) at anterior tibial and DP, 1 set of balloon inflate/deflate 2 3 4 Catheter exchange during this time 4 3 2 11
Provocation response Case report OMNIA trial 200% Sex M Age (yrs) 65 Diabetes Type 2 Foot Side Right Rutherford Class 5 180% 160% 140% 120% 100% 80% 60% 40% 20% 0% Before PTA 3 Months 1 month
Provocation response Fallbeispiel OMNIA Studie Sex M Age (yrs) 65 Diabetes Type 2 Foot Side Right Rutherford Class 5 200% 150% 100% 50% 0% 1 month 6 months Before PTA 3 Months 6 Months
Tissue oxygen index Provocation response Wound Area cm^2 TBI [-] ABI [-] Subject: 03-001 Demographics Sex M Age (yrs) 65 Diabetes Type 2 Foot Side Right Rutherford Class 5 Wound Right second toe Therapy 1. Treated popliteal during this time via 1 set of balloon inflate/deflate 2. Treated anterior tibial during this time via 5 sets of balloon inflate/deflate 3. Use DCB (Lutonix 2.0/80mm) at anterior tibial and DP, 1 set of balloon inflate/deflate Lumee: Intra-operative reperfusion Average LOI increase was 20.5 [-] was very high (in 93 rd percentile out of 19 sampled subjects) Lumee: Functional Assessment Recovery modulation at 1-3 months of >100% of baseline is a feature consistent with non-responding patients Pre-Op Discharge 1 Month 3 Month 6 Month Wound 2 2 2 1 3 Gangrene 2 3 2 0 3 Ischemia 3 3 3 N/A 3 Infection 2 2 N/A N/A 2 WIFI Risk 4 4 4 1 4 Toe Pressure [mmhg] 40 65 120 100 54 ABI 0.89 1.17 1.13 1.41 0.8 TBI 0.197 0.346 0.618 0.641 0.39 Wound Images Pre-Tx 1 month 3 month 6 month No photo available (1) (2) (3) Pre Dis 1mo 3mo 6mo Pre Dis 1mo 3mo 6mo 40 20 0 Pre Dis 1mo 3mo 6mo 200% 150% 100% 50% 0% Pre Dis 1mo 3mo 6mo
Pre-procedure (day 1) Discharge (day2 ) Provocation response data 1- Month (day 23) 3-Month (day 96) 2 3 Extended hyperemia observed at 1- and 3- month follow ups 4 15
Tissue oxygen index Provocation response Wound Area cm^2 TBI [-] ABI [-] Subject: 03-002 Demographics Sex M Age (yrs) 79 Diabetes Type 2 Foot Side Left Rutherford Class 5 Pre-Op Discharge 1 Month 3 Month 6 Month Wound 1 1 0 0 0 Gangrene 1 0 0 0 0 Ischemia 3 1 0 0 0 Infection N/A N/A N/A N/A 0 WIFI Risk 3 1 1 1 1 Pre Dis 1mo 3mo 6mo Wound Left first toe Therapy 1. Treated SFA and popliteal a. via 4 sets of balloon inflate/deflate 2. Treated fibularis a. via 3 sets of balloon inflate/deflate and stent 3. Balloon 1X Lumee: Intra-operative reperfusion Average LOI increase of 15.6 [-] was high (in 73 rd percentile out of 19 sampled subjects) Lumee: Functional Assessment Maximal recovery modulation at 1-3 months of <100% is a feature consistent with healing patients Toe Pressure [mmhg] 32 135 88 62 62 ABI 0 0.39 0.91 0.611 0.71 TBI 0.177 0.758 0.489 0.344 0.41 (1) (2) (3) Pre Dis 1mo 3mo 6mo 0,02 0,01 0 Pre Dis 1mo 3mo 6mo 200% 150% 100% 50% 0% Pre Dis 1mo 3mo 6mo
Lumee sensors show slow response until last balloon treatment and catheter removal Treated SFA and popliteal a. via 4 sets of balloon inflate/deflate Treated fibularis a. via 3 sets of balloon inflate/deflate and stent 1 x 2 3 Unable to locate sensor 4 4 2 17
Pre-procedure (day 1) Discharge (day2 ) Provocation response data 1- Month (day 23) 3-Month (day 96) 2 3 No hyperemia observed at 1- and 3- month follow ups 4 18
OMNIA compares measures of reperfusion with wound healing Clinical observations Lumee Intrasurgical [LOI] Lumee 1-mo Functional Assessment [%] Site Subject Diabetes WIFI Risk @ 1 month @ 3 month @ 6 month Wound Area Toe Pressure Angiosome Channel 2 Channel 3 Channel 4 Channel 2 Channel 3 Channel 4 01 002 Type II 4 Improved Improved Improved N/A Bypass Bypass Bypass 26.7 50.5 57.0 01 003 Type II 1 No Change Worsening Worsening Maybe 5.9 6.2 2.7 190.7 39.1 01 004 Type II 1 Improved Improved Worsening No -3.6-0.4 3.1 126.9 111.8 151.6 01 007 Type II 4 Worsening Worsening Worsening Maybe -3.6-0.7 1.4 49.1 146.7 143.1 01 009 Type II 1 No Change Improved Improved Yes 5.2 24.8 3.7 33.2 01 010 Type II 2 No Change No Change No Change Maybe -13.5-9.3 0.9 9.8 34.9 190.1 01 012 Type II 1 Worsening Improved Improved Yes 52.5-0.1 2.1 0.0 174.4 38.5 01 013 Type II 2 Improved Improved N/A 30.6 36.2 84.1 01 015 Type II 1 Improved Improved Yes 35.4-15.1-8.6 62.5 65.7 113.3 WIFI Risk Clinical observations 02 001 None 4 Improved Improved Improved Yes 16.7 4.8-2.7 34.7 71.0 02 Risk 002 of amputation Wound healing transitions between follow Intra-op, reperfusion modulation Unconfirm 2 Maybe 13.8 1.6-6.4 02 assessed 003 Unconfirm by WIFI at 1 Worsening Worsening up visits assessed Improved from clinical observations Post-op, recovery modulation Maybe 5.1 12.8 9.6 67.1 23.0 0.0 02 enrollment 004 Type II 2 No Change Improved Evaluated Improved by Profusa using photos and No -0.8-5.7 19.5 44.9 95.4 22.7 02 005 Type II 1 N/A Characterizes initial wound burden wound size Lumee Results 03 001 Type II 4 No Change Improved Key Worsening Wound status Maybe 2.0 24.7 34.9 03 002 None 3 Improved Improved Improved Healing Yes 19.6 11.6 Positive Reperfusion20.0 03 003 Type I 3 No Change Improved No Change No -1.9-0.4-1.3 15.8 47.0 18.8 Elevated Hyperemia 03 004 Type II 2 Improved Improved Maybe 32.0 10.3 24.3 75.6 46.2 Worsening 03 005 None 3 Worsening Maybe 18.6 25.3 12.5 Key Lumee Response
Intra-op LOI [-] Intra-operative LOI change is correlated with TBI Analysis performed on subjects completing 3-month follow up with TBI reported (n=9) r=0.53 p<0.03 For each subject, change in TBI after revascularization is plotted on x-axis, and intra-op change in LOI is plotted on y-axis Marker size indicates risk of amputation assessed by WIFI scores at enrollment Marker color represents wound healing (green), no change (yellow), or worsening (red) through 3 month follow up TBI change post-op [-] Results show highly positive correlation between LOI and TBI
Summary and Future Plans Initial phase of study: (first 21 subjects enrolled) Goal: establish feasibility and generate hypotheses Preliminary findings: Intra-op LOI measurements of reperfusion reveal functional benefit of intervention Post-op LOI evaluation of microvascular function may be indicator of long term healing Next phase of study: (next 30 subjects enrolled) Goal: refine methods and test hypotheses Ongoing questions: Refine classification algorithms using both intraop and post-op measurements to predict wound healing
Acknowledgements Clinical Research Team Medical University Graz, Austria Marianne Brodmann M.D. St Franziskus-Hospital Munster, Germany Theo Bisdas, M.D. Arne Schwindt M.D. Hanusch Hospital Vienna, Austria OMNIA PIs Martin Werner M.D. Profusa San Francisco, USA Kerstin Rebrin, M.D., Ph.D. Kit Yee Au-Yeung, Ph.D. Wayne Menzie, Ph.D. Stephen Kanick, Ph.D. Medical Advisory Committee Peter Schneider, M.D. Miguel Montero-Baker M.D. Medhi Shishehbor, D.O, Ph.D. Michael Conte, M.D. 22