The ClearWay™ RX Local Therapeutic Infusion Catheter

ClearWay (Atrium Medical, Hudson, NH) is a low-profile, rapid-exchange therapeutic infusion catheter and is indicated for localized perfusion of various diagnostic and therapeutic agents into the coronary and peripheral vasculature. The ClearWay therapeutic infusion catheter enables local drug delivery to reach approximately a 500-fold greater drug concentration versus systemic delivery. How does this catheter work? The ClearWay catheter is a microporous PTFE balloon, available in two different forms. One is a monorail .014”-compatible device primarily designed for use in the coronaries, although it can be used in the vasculature as well. The company also has another version, an .035”-compatible over-the-wire device. It comes in significantly larger diameters than a coronary balloon and is specifically designed for vascular therapeutic drug delivery purposes. This device is FDA approved for any catheter drug delivery. Essentially, a drug is injected through the balloon, which spontaneously inflates as the drug is injected. The drug is infused through the balloon, into the target area. Based on multiple publications and our clinical experience, glycoprotein (GP) IIb/IIIa inhibitors show the most promise, but nitroglycerin, sodium nitroprusside, tPA, retevase, and paclitaxel have all been utilized in different centers, based on the indication and the procedure.¹ How long does the drug actually stay at the site? This goes back to the mechanism of action of the catheter. As the balloon inflates while you are injecting the drug — based on the predetermined diameter of the balloon — you actually slow down the coronary flow. The localized concentration of the drug is significantly higher and it remains at the site for a great deal longer than if you just injected a drug through the guide catheter. Using a guide catheter, within two or three cardiac cycles, there is total and complete clearance of the drug, out of the coronary artery into the systemic circulation. In contrast, with the ClearWay catheter, because you are inflating a balloon and injecting a drug, there is some slowing of the coronary flow, resulting in significantly increased drug residence time in the area. Similarly, in the leg, the same thing happens. Because of the diffuse and multi-segment disease present in most of the cases in which we use this catheter, there is increased residence time of the drug. I don’t think we can measure how long these molecules reside in these vessels, but they are definitely there much longer than when injecting through a sheath or a catheter, where the flow is not slowed. How long does it take to set up and use? The ClearWay catheter is very simple. It requires a quick flush, and then is ready to use. You take the syringe of the drug, whatever the drug may be, connect it with the catheter, and advance it into the artery, based on whether you have chosen a monorail device or whether you have chosen an over-the-wire device. Place the catheter at the site of interest, and then just deliver the drug. Timing depends on the amount of drug you are delivering. For example, if you wanted to deliver 10ccs of abciximab, which is a very common dose that we use, it usually takes about 60-70 seconds. How do you decide on the size of the catheter? That is an excellent question. Our understanding of this device has evolved over time. Initially, we were utilizing large diameter catheters matched to the size of the vessel. The challenge with this strategy is that thrombus often obscures an underlying stenosis, making it difficult to track a larger balloon in a compromised vessel. What really should be done is to match the size of the device to the lumen of the vessel. For example, if you have a totally occluded coronary artery or 90% stenosed vessel, we would recommend a 1.0mm x 20mm catheter, as it will produce the desired contact between the thrombus and device. I usually use a 1.0mm or 1.5mm diameter ClearWay catheter. In the lower extremities, I most frequently use a 2.0mm x 50mm device in the femoropoliteal segment and shorter catheters in below-the-knee distribution. How does the catheter fit into current treatment? In an indication such as a thrombus-containing lesion in the coronaries, the use of intracoronary abciximab has been around for some time, but the majority of intracoronary abciximab use was through a guide catheter. Physicians were just injecting the drug through the guide catheter, and I have also seen drugs injected through an end-hole catheter in the coronaries. The ClearWay catheter is a new concept as far as the thrombus-containing coronary lesion is concerned. In contrast, thrombolytic therapy in lower-extremity thrombotic lesions has been popular. Ultimately, the ClearWay catheter is a new way of delivering tPA, which is potentially more effective than just injecting through a sheath or through an end-hole catheter due to greater contact of the lytic agent with thrombus while using this device. Experiments are underway to determine the utility of this device in peripheral arterial restenosis for anti-restenotic therapy delivery. The IRRITAX trial is the first trial to study this concept, led by Dr. Thomas Hennebry at Oklahoma University Medical Center. It will be presented at C32010 on June 21st in Baltimore (www.C3conference.net). Dr. Waksman and his group from Washington Cardiology Center have recently published their favorable experience with this device in no-reflow cases. What’s your history with the ClearWay catheter? We have done approximately 700 cases at our center with this catheter, utilizing it in many different circumstances, such as ST-elevation myocardial infarction (STEMI), non-STEMI, thrombus-containing lesions, vein grafts, no reflow or slow flow, complex femoral popliteal occlusions, cases of critical limb ischemia, and also thrombus-containing lower-extremity lesions. You just completed a series on critical limb ischemia patients. Can you describe your experience? Yes, we did a retrospective analysis. Our analysis contained 70-plus patients with complex, multi-vessel disease. All of these patients had critical limb ischemia, with non-healing ulcers, gangrene, rest pain, and very complex lower extremity arterial disease. We used a vascular ClearWay catheter to inject abciximab prior to an atherectomy procedure, which was the mainstay of therapy in the majority of these patients. What we have seen so far is that the likelihood of distal embolization was close to zero, in contrast to published distal embolization rates of anywhere from 7-10% in these types of cases. In addition, ClearWay catheter-treated patients had a significantly lower risk of re-occlusion of these vessels at 6-month follow up. Flow in the pedal vessels was significantly improved, and because the distal embolization risk is so small, especially with the use of abciximab, the likelihood of wound healing is going to be much greater, and the time to wound healing is going to be shorter. Due to better pedal arch flow, less distal embolization and less reocclusions, we did see a much shorter time to wound healing in these patients. Is there any role for this device with calcified plaque? We certainly have used intra-arterial abciximab with Clearway in long, complex calcified lesions requiring rotational/orbital atherectomy. If you recall, in prior investigations with rotational atherectomy in the calcified coronary arteries, abciximab is known to reduce no-reflow phenomenon. Similarly, in the complex lower extremity disease and complex coronary disease, we also see improvement in the flow and less risk of distal embolization with localized, high concentration of abciximab. It’s just a better way of delivering abciximab than giving it IV. How does the balloon impact the vessel wall? In vitro testing done by Dr. Renu Virmani has looked specifically at the potential for balloon-related injury to the vessel wall. The in vitro testing has shown that this balloon delivers the drug atraumatically, which limits vessel injury, unlike a regular percutaneous transluminal coronary angioplasty balloon, where you may have significant potential balloon injury that can then lead to other problems. What research has been done regarding the effect of antiplatelet or thrombolytic therapies delivered in a localized, concentrated fashion? There is some in vitro data looking at the concentration of a GP IIb/IIIa inhibitor and its effect on thrombus. Specifically, Moser and colleagues have shown that a very high concentration of a GP IIb/IIIa inhibitor, in excess of 100x the systemic concentration, almost acts like thrombolytic therapy. It breaks apart the bond within the thrombus and fibrin strands. With the current limitations of angiography, it is difficult to measure thrombus dissolution in patients, except by looking at clinical surrogate markers, such as improvement in flow, less risk of distal embolization, less chance of no-reflow, and improved myocardial blush grade. In the lower extremities, we also see less distal embolization and better pedal flow; so again, this is the way to clinically evaluate the drug performance. There have been two Italian studies, COCTAIL I and II. COCTAIL I was done by Dr. Francesco Prati, from Rome Heart Research. He actually utilized optical coherence tomography (OCT) in patients with non-STEMI to assess the amount of thrombus in the coronary artery, followed by ClearWay use and abciximab. The trial compared this to a guide catheter delivery of abciximab, and re-measured the thrombus core using OCT. What Dr. Prati showed in the COCTAIL I trial, presented at TCT 2009, is that the thrombus score change was significantly and statistically better with ClearWay-delivered abciximab compared to guide catheter administration (34% vs 4%, p=0.002). This trial provides clinical evidence, in vivo patient evidence, of the effect of these drugs in a localized fashion. In our personal experience doing multiple coronary and lower extremity cases, we have consistently seen improved flow and reduced case complications with intracoronary/arterial abciximab using the ClearWay catheter. In fact, at Harrisburg Hospital, use of this device is now almost the standard of care in patients who do present with a heavily thrombotic-burdened vessel. Whether it is a vein graft or a native coronary artery, in a STEMI or a non-STEMI, the use of intracoronary abxicimab delivered in a localized, concentrated fashion, has significantly reduced the thrombus burden by angiography, reduced the likelihood of no-reflow, and improved myocardial blush grade in our experience. Post PCI, are these patients treated as patients who have received a GP IIb/IIIa inhibitor? Yes, there is no difference in treatment. If you ask the majority of the physicians who do PCI in the U.S. and in foreign countries, the main concern in using GP IIb/IIIa inhibitors is access site bleeding. The problem of access site bleeding occurs when the dose of the heparin is not controlled. In our laboratory, when we use GP IIb/IIIa inhibitors, whether through a ClearWay catheter, IV or through a guide catheter — no matter what the route of administration — our heparin dose is very controlled. For a coronary case, and also in the majority of vascular cases, we use heparin at 60-70 U/kg. That keeps the ACT between 200-230, the ideal ACT in the setting of a GP IIb/IIIa inhibitor, and reduces the likelihood of bleeding. The CRYSTAL MI trial, now underway, is a randomized protocol of intracoronary abciximab with ClearWay versus IV abciximab. We have done the first 40 patients and, in fact, have had no bleeding in the intracoronary abciximab arm. The second clinical ‘trick’ we use is that we do not run an IV abciximab infusion post procedure, whether it is a coronary or vascular procedure. Our opinion is that the bolus dose is the most important part of GP IIb/IIIa administration. Once the patient is off the table, no GP IIb/IIIa inhibitor is required, because these patients almost always have received a loading dose of clopidogrel or prasugrel. By the time the effect of the abciximab has begun to wear off, their oral antiplatelet therapy has kicked in, meaning there is adequate platelet inhibition, and a prolonged infusion is not required. Keeping these two factors in mind, with the addition of good sheath management post procedure, has reduced our bleeding complications to almost zero. In fact, we haven’t had any fatal bleeds in our vascular or coronary experience with the use of intra-arterial abciximab. What do you think is the future of this device in coming years? Our understanding has evolved a great deal with this device and the utility of certain agents delivered in high concentration, especially GP IIb/IIIa inhibitors. Multi-center randomized trials such as INFUSE AMI will evaluate its clinical benefit in a greater number of patients. We are also learning from our experience that combining mechanical thrombectomy, such as aspiration, with a localized, high-concentration GP IIb/IIIa inhibitor, addresses difficult-to-treat, wall-adherent thrombus in difficult thrombus-containing lesions. It has been demonstrated in prior investigations that the use of drug-eluting stents on large thrombus burden may worsen the outcome. The ClearWay catheter will add to our armamentarium in dealing with this difficult subset and will reduce ultimate cost. The role in peripheral arterial interventions is being investigated at many centers. Many different drugs are now used, including GP IIb/IIas, lytic agents, anti-restenotic therapy and vasodilators, depending on the clinical indication. In addition, the device is easy to use, without the loss of wire, and repeated use in one procedure is possible. Moreover, in my practice, I have observed fewer complications and readmissions with the use of this technique, making it a cost-effective alternative. I do expect greater acceptance of this technique in routine clinical practice. ¹All drugs, with the exception of nitroglycerin and tPA, are not approved for intra-arterial delivery. Disclosure: Dr. Dave serves and receives honorarium as a consultant, speaker and trainer for Atrium Medical Corporation. Dr. Dave can be contacted at: rdintervention@ yahoo.com

NULL