Results from the First-in-Human Study of the Caterpillar™ Arterial Embolization System

Twenty patients were treated in the prospective, multicenter, single-arm study entitled, Clinical Use of the Caterpillar™ Arterial Embolization Device System for Arterial Embolization in the Peripheral Vasculature (CHRYSALIS). Investigators at five centers in New Zealand and Australia enrolled patients between September 2019 and September 2020 under a protocol approved by their institutional ethics committees. Patients provided written informed consent prior to participation in the study, and procedures were conducted in accordance with the Declaration of Helsinki, good clinical practices, and applicable healthcare laws in both countries. Data were collected by the investigators using standardized web-based clinical report forms. An independent medical monitor reviewed all complications for adverse event (AE) trends. The study was sponsored by C.R. Bard/Becton, Dickinson and Company and was registered on clinicaltrials.gov [NCT04090320] prior to patient enrollment.

Patients were treated with the Caterpillar™ or Caterpillar™ Micro Arterial Embolization Device (Becton, Dickinson and Company, Tempe, AZ, USA), self-expanding vascular occlusion devices intended as permanent implants for peripheral arterial embolization. The devices, described briefly in two previous publications and depicted in Fig. 1, are composed of a cobalt-chromium stem, opposing nickel-titanium (i.e., nitinol) fibers, a polyurethane and polyethylene occlusion membrane, and platinum-iridium radiopaque marker bands [8, 9]. When deployed, the nitinol fibers form an opposing concave, hour-glass shape designed to provide stability inside the artery and encourage thrombosis while the occlusion membrane lining the inside of the proximal fibers is designed to block blood flow and support rapid occlusion. Caterpillar devices are packaged sterile and intended for single use, and the system includes the implant, loader, dispenser hoop, torque tool, and detachable delivery wire. There are two Caterpillar device sizes (038 and 056) available for arteries with a target diameter of 3 to 7 mm and a landing zone of 26 to 37 mm and one Caterpillar Micro device (027) designed for arteries with a target diameter of 1.5 to 4 mm and a landing zone of ≥ 16 mm (Table 1). The device sizes of 027, 038, and 056 refer to the inner diameter compatibility of the delivery catheter in inches (i.e., 0.027″, 0.038″, and 0.056″).

Patient inclusion and exclusion criteria are detailed in Table 2. Eligible patients had a peripheral arterial embolization site or multiple sites that could be treated with an appropriately sized study device. Angiography was required to demonstrate that the embolization site was in an artery that could accommodate the device diameters and lengths. Patients were excluded if the embolization site was in a vein; in a head, neck, heart, or coronary artery; crossed highly locomotive joints or muscle beds (e.g., elbow, hip, knee, shoulder, thoracic inlet/outlet); or was in a high-flow vessel with a significant risk of migration (e.g., pulmonary arteriovenous malformations). Patients receiving anticoagulation or antiplatelet therapy that in the opinion of the investigator would clinically interfere with study outcomes were also excluded (e.g., direct thrombin inhibitors, factor Xa inhibitors, and vitamin K antagonists).

The primary outcome measure was technical success defined as peri-procedural occlusion of the embolization site confirmed by the investigator using angiography. The primary safety measure was 30-day freedom from device-related serious adverse events (SAEs) defined as adverse events caused by the embolization device that led to death or serious deterioration in health (e.g., prolonged hospitalization, permanent impairment, or life-threatening injury or illness). Secondary measures included time to occlusion reported as the percentage of embolization sites occluded during the first ten minutes after deployment (angiographic visualization by the investigator at one-minute intervals); freedom from clinically-relevant recanalization through 30 days defined as freedom from blood flow through the treatment site that required reintervention; freedom from clinically-relevant migration of the embolization device requiring reintervention through 30 days, and freedom from device- or procedure-related adverse events (AEs) through 30 days. In addition, investigators answered three questions based on their use of the device during the procedure: (1) Was the device easily tracked and delivered to the target embolization site? (2) Was fluoroscopic visibility of the device acceptable? (3) Was the device accurately deployed at the target site? All answers were qualitative based on the investigator’s opinion and answered “yes” or “no”.

Patients were enrolled in the study after providing written informed consent and receiving a comprehensive physical examination, preoperative laboratory tests, and angiographic assessment of eligibility. Once an appropriately-sized device was chosen based on vessel anatomy and dimensions, the device loader was advanced through a Tuohy–Borst adapter until seated against the delivery catheter hub. The Caterpillar device was advanced from the loader through the delivery catheter to the catheter tip using the attached delivery wire. Patients were considered treated when the embolization device exited the system loader and entered the delivery catheter. The delivery catheter was positioned just distal to the embolization site, the device was held stationary using the delivery wire, the delivery catheter was retracted to deploy the device, and the delivery wire was turned counterclockwise using the supplied torque tool to separate it from the deployed device. The Caterpillar device could be recaptured and repositioned after deployment of the distal positioning zone; if, however, device position was incorrect after the detachment zone was deployed, both the device and delivery catheter had to be recaptured by the guiding sheath, removed together, and discarded. The Caterpillar Micro device could not be recaptured in the microcatheter and repositioned once the distal fiber segment was deployed.

A single device per embolization site was recommended in the protocol; however, additional devices could be deployed to achieve occlusion if required. The protocol recommended that unless a delay impacted patient safety, the investigator should wait at least five minutes before deploying another embolization device or agent so that the original study treatment could be evaluated. Medications and adjunctive medical therapy before, during, and after the study procedure were administered per the investigator’s standard of care and documented through completion of the study. Adjunctive embolization devices or agents were allowed to treat the target site if deemed clinically necessary and were documented accordingly. An in-office or telephone follow-up visit was performed at 30 (−7/ + 21) days, and all available medical records and embolization site images were reviewed and documented.

CHRYSALIS was designed as an exploratory study. The sample size was based on the potential adequacy of data to meet the study objectives, not statistical considerations. The analysis population consisted of all patients treated with the study device. There were no statistically-tested hypotheses. Data collected were observational and were summarized using descriptive statistics including frequency counts and percentages for categorical variables and means and standard deviations for continuous variables.

Twenty-nine patients were consented and enrolled at five sites while 20 patients were treated at four of the sites; nine patients failed to meet the eligibility criteria for inclusion in the trial (Fig. 2). Baseline patient demographics and medical histories are summarized in Table 3. Patients were on average 73.4 ± 8.5 years old, and 85% were male. Risk factors included hypertension (90%), past or present smoking (85%), and dyslipidemia (70%) while co-morbidities included aortic disease (60%), peripheral arterial disease (60%), and coronary artery disease (45%). Embolization site characteristics and procedural details are summarized in Table 4. Twenty-four peripheral arterial embolization sites were treated across seven arterial locations with the most common areas of treatment in accessory renal arteries, internal iliac arteries, iliac artery branches (Fig. 3), and inferior mesenteric arteries (Fig. 4). The mean treated artery diameter was 4.5 ± 1.2 mm with an average landing-zone length of 44.5 ± 12.7 mm. Sixteen patients (80%) had one site treated while four patients (20%) had two sites treated.

Primary and secondary outcomes are summarized in Table 5. Nineteen patients (95%) completed the study (i.e., one patient died during a subsequent EVAR procedure). The primary outcome measure, technical success or successful occlusion of the target embolization site confirmed by angiography during the procedure, was 100% (24/24 sites). All but two embolization sites (91.7%) were occluded with one device; an accessory renal artery was treated with two Caterpillar 038 devices and an internal iliac artery had a Caterpillar 056 device and 038 device deployed to achieve full occlusion. The primary safety outcome, the proportion of patients free from device-related SAEs through 30 days, was 94.7% (18/19 patients).

The mean device deployment time, defined as the time from device introduction into the delivery catheter until detachment, was 1.8 ± 1.0 min. The mean overall procedure duration was 11.7 ± 8.6 min, and the mean fluoroscopy exposure time was 241.0 ± 290.7 s. No arteries required adjunctive embolization with other devices or embolic agents, no sites required re-embolization, and no devices migrated from the target site requiring a reintervention through 30 days. Time to occlusion was tracked angiographically by the investigator at one-minute intervals during the embolization procedure; 62.5% of the 24 treated sites occluded within 3 min, 70.8% occluded within 5 min, and 91.6% occluded within 10 min of device deployment. Two sites took more than ten minutes to occlude, but full occlusion was achieved before the end of the embolization procedure. A total of 84.2% (95% CI: 60.4%, 96.6%) of patients were free from device- or procedure-related AEs at 30 days. Three procedure-related AEs were reported. One patient experienced right buttock pain approximately two weeks after subsequent EVAR, deemed by the investigator as related to the embolization procedure. Two patients experienced gastrointestinal disorders deemed possibly related to the procedure by the investigator; one was an SAE requiring additional hospitalization (possibly device- or procedure-related) and the second patient was seen by a vascular registrar and treated with paracetamol (acetaminophen). The severity of the three events was reported as mild, and the symptoms resolved without further intervention. Finally, 100% of investigators answered “yes” to the questions of whether the device was easily tracked and delivered to the target embolization site and was deployed accurately. The third question of whether the device was fluoroscopically visible during the procedure was answered “yes” by 96.4% of investigators. One investigator reported that the radiopaque markers on a Caterpillar 027 Micro device were difficult to visualize under fluoroscopy; the device, however, tracked easily and was delivered accurately to the embolization site without a reported AE.