Clinical Results

The Occlusion Perfusion Catheter™ (OPC), a universal delivery system, is a multi-lumen balloon catheter designed to temporarily occlude a specific region from blood flow and then locally deliver physician-specified diagnostic and/or therapeutic agents into the peripheral and coronary vasculature. The OPC can be repositioned for multiple treatments within the same patient.
 
The use of an occlusion perfusion catheter to deliver paclitaxel to the arterial wall. Atigh MK, Turner E, Rittlemeyer B, Erwin M, Christians U, Yazdani SK, Cardiovasc Ther. 2017 Apr 26. doi: 10.1111/1755-5922.12269. View Paper
 
Abstract
 
AIM:  Non-stent drug delivery platforms have recently emerged as an alternative treatment of peripheral arterial disease. Perfusion catheters have the potential to directly deliver anti-proliferative agents to the medial arterial layer to prevent restenosis. The purpose of this study was to therefore determine the effectiveness of a perfusion catheter to deliver paclitaxel, a proven anti-proliferative agent, to combat restenosis.
 
METHODS:  A bench-top model was utilized to determine the varying parameters of a novel occlusion perfusion catheter to maximize paclitaxel delivery using pharmacokinetic evaluation and fluorescent microscopy. Parameters tested included concentration of paclitaxel, delivery pressure, duration of delivery, and the use of an excipient. In addition, bilateral rabbit iliac arteries were treated with the perfusion catheter and pharmacokinetic evaluation performed at 1 hour, 1 day and 3 days.
 
RESULTS:  Bench-top testing demonstrated uniform and circumferential penetration of paclitaxel within the treated arteries. The results of the ex vivo test identified two groups with and without an excipient with similar loading conditions (with excipient: 15.4±8.6 ng/mg vs. without excipient: 8.9±6.9 ng/mg, p = 0.77). The in vivo pharmacokinetic analysis of these two groups demonstrated the use of contrast agent increased arterial paclitaxel levels and maintained initial paclitaxel dosing up to 3 days (With excipient: 1 hr: 107±62 ng vs. 3 days: 40±23 ng, p = 0.824; No excipient: 1 hr: 247±120 ng vs. 3 days: 2.92±2.9 ng, p=0.009).
 
CONCLUSIONS:  These results demonstrate the feasibility to deliver paclitaxel directly to the medial layer of an artery via a perfusion catheter.
 
Delivery of paclitaxel to arterial segments via a perfusion catheter: an ex vivo and in vivo study. Atigh MK, Turner E, Rittlemeyer B, Erwin M, Christians U, Yazdani SK. 2 iC42 Clinical Research and Development, University of Colorado Denver, Aurora, CO. View Poster
 
Abstract
 
Purpose: Interventional treatment strategies aimed at patients with peripheral arterial disease (PAD) is currently limited due to restenosis. Stents, either bare or drug coated, fracture due to severe mechanical movement of peripheral arteries. The recently FDA approved drug coated balloons have poor drug retention and deposit their anti-proliferative drug on the luminal surface, potentially delaying vascular healing and re-endothelialization. Furthermore, treatment of below-the-knee lesions have not shown improvement versus plain old balloon angioplasty. The goal of this project was to thus demonstrate the feasibility of a perfusion catheter to deliver anti-proliferative drug into the arterial wall using ex vivo and in vivo models. Additionally, we wanted to determine the relationship between treatment chamber pressure and drug penetration.
 
Materials and Methods: Paclitaxel was delivered in an ex vivo circulatory system to harvested swine carotid arteries using a perfusion catheter. To visualize drug distribution following delivery, a fluorescently labeled paclitaxel was delivered via the perfusion catheter. To quantify paclitaxel dosage, pharmacokinetic analysis was performed at 1 hour, 1 day and 3 days. In vivo assessment of the perfusion catheter was performed in a rabbit ilio-femoral injury model. Histological analysis as well as pharmacokinetic analysis was performed to determine any adverse impact of the paclitaxel and to quantify drug kinetics. A total of 12 rabbits were utilized for this study. Assessment of drug penetration in relation to treatment chamber pressure was achieved via computer model with pressure-dependent geometric and material properties.
 
Results: Confocal analysis demonstrated the perfusion catheter was successful in delivering the fluorescent paclitaxel uniformly within the media and adventitial layer, circumferentially and longitudinally, at both 1 hour and 3-day post treatment.  Pharmacokinetic analysis of arterial tissue demonstrated paclitaxel delivered by the perfusion catheter maintained drug levels up to 3 days (5.11±8.37 ng/mg). The two-dimensional computer model demonstrated non-linear relationship between treatment chamber pressure, viscosity and drug penetration.
 
Conclusions:  In summary, the completed preclinical studies illustrate the capability of the perfusion catheter to deliver the anti-proliferative agent paclitaxel in a clinically relevant rabbit ilio-femoral injury model.  Confocal analysis demonstrated uniform distribution of the paclitaxel agent, circumferentially and longitudinally, within the media and adventitia.  The computational model demonstrates the significance of real-time pressure measurement of the treatment chamber. Taken together, the studies exhibit the potential of the perfusion catheter as a novel device to deliver anti-proliferative agents locally to the vascular wall.      
 
Clinical Studies  – COPPER A and COPPER B (BTK)
Prospective, non-randomized, first-in-human
 
Purpose:  The purpose of the COPPER-B study is to assess the feasibility, safety, and initial efficacy of paclitaxel administration using the OPC for the prevention of restenosis in infrapopliteal de novo and restenotic lesions and occlusions using a novel catheter, the OPC.
 
Primary Safety Endpoint: Freedom from major adverse events (MAEs) at one (1) month, three (3) months, and six (6) months, defined as thrombosis, major amputation in the target limb (amputation above the metatarsals), and target limb related death.
 
Primary Efficacy Endpoint:  Freedom from clinically driven target lesion revascularization (CD-TLR) at six (6) months.
 
Initial Results:  Initial results demonstrate the OPC is safe with promising signals of enhanced paclitaxel efficacy 
 
Treatments to Date:
  • IRB approved 
  • 12 U.S. sites
  • Treated 67 patients
  • 220/222 (99.1%) successful OPC placements with 68 catheters
  • 3.3 placements per OPC on average
  • No Major Adverse Events (MAEs)
  • No device-related AEs, UADEs or SAEs 
OPC Performance in Rabbit Model Study – Demonstrating Confocal Analysis1
  • Successful delivery of fluorescent paclitaxel
  • Uniformly within media and adventitial layer
  • Circumferentially and longitudinally
  • 7x increase in PK over predicate device
1Data on file – Advanced Catheter Therapies