Innovation: Clot Detection Mechanism Makes for Intelligent Aspiration

Newest Generation of Indigo® Aspiration System Primed to Treat Pulmonary Embolism: JACC-CI Publishes EXTRACT-PE Data

 

The latest round of excitement for Penumbra, Inc.’s Indigo® Aspiration System — first sparked in early 2020 with the announcement of a new pulmonary embolism (PE) indication — continues to generate interest due to the new PE indication for Lightning™12 and the recent publication of EXTRACT-PE data in the Journal of the American College of Cardiology: Cardiovascular Interventions.

EXTRACT-PE, the first prospective trial of the Indigo System, successfully met its primary endpoints, demonstrating the safety and efficacy of the Indigo System for aspiration mechanical thrombectomy in patients with acute pulmonary embolism. Results showed improvement in right ventricular (RV) function. Additionally, the study data showed low rates of mortality and major bleeding, no cardiac injury, and median procedure times of 37 minutes. The paper, Indigo Aspiration System for the Treatment of Pulmonary Embolism: Results of the EXTRACT-PE Trial,1 was published online in January 2021. Trial results were initially presented at the Vascular InterVentional Advances (VIVA) Annual Meeting in 2019.

 

Pulmonary Embolism

Researchers have noted that many patients who have died from COVID-19 — the deadly disease caused by SARS-CoV-2 — had formed blood clots throughout their bodies, including in their smallest blood vessels. This unusual clotting, one of many life-threatening effects of the disease, has caused multiple health complications, from organ damage to heart attack, stroke, and pulmonary embolism.2 An increasing concern in COVID-19 patients, PE occurs when blood clots get caught in the arteries of the lungs. Blood clots in the lungs can block the lungs from absorbing oxygen, causing strain on the heart and other organs. According to the American Heart Association, PE affects roughly 340,000 Americans per year.

The formation of a blood clot in an artery or vein is called thrombosis, an often-preventable cause of conditions such as deep vein thrombosis (DVT) and acute ischemic stroke, amongst others. DVT is a blood clot that partially or completely blocks blood flow through a vein deep in the body, particularly the lower leg, thigh, or pelvis. DVT puts people at higher risk of PE because a piece of clot can break free from its original location, travel through the bloodstream, and block blood flow to the lungs.4

 

The EXTRACT-PE Trial

The EXTRACT-PE Trial was a prospective, single-arm, multicenter trial under an Investigational Device Exemption (IDE) from the U.S. Food and Drug Administration (FDA) that evaluated the safety and efficacy of the Indigo Aspiration System (CAT8) in the treatment of acute pulmonary embolism. The study enrolled 119 participants across 22 U.S. study centers.

The primary efficacy endpoint was met with a mean reduction in (RV)/left ventricular (LV) ratio of 0.43, corresponding to a 27.3% reduction, at 48 hours after intervention. The primary safety endpoint was reached with a low major adverse event composite rate of 1.7% within 48 hours. The major adverse event composite included device-related death, major bleeding, and device-related serious adverse events as adjudicated by the clinical events committee. Additional data reported included median time of Indigo System usage (37 minutes) and median ICU stay (one day). No intraprocedural thrombolytic drugs were used in 98.3% of patients. The authors stated, “The median Indigo device introduction to removal time was 37.0 min, which is the fastest published time in prospective mechanical thrombectomy studies for acute PE.”

 

Central Illustration Primary Efficacy and Safety Endpoint Results of the EXTRACT-PE Trial

Central Illustration

CI = confidence interval; LV = left ventricle; N/A = not applicable; RV = right ventricle.
Indigo Aspiration System for Treatment of Pulmonary Embolism, DOI: (10.1016/j.jcin.2020.09.053)

 

In his editorial, titled Mechanical Thrombectomy in Pulmonary Embolism: Ready for Prime Time?5 and published in the same journal issue, Kush R Desai, MD, writes that one notable difference between the EXTRACT-PE and FLARE trials “was the device-specific treatment time, which was faster in the EXTRACT trial (median 37 min) than in the FLARE trial (approximate mean 57 min). He writes that EXTRACT-PE trial results “are an important addition to the growing body of evidence on endovascular mechanical thrombectomy for the treatment of PE in select patients.”

Victor F. Tapson, MD, pulmonary critical care specialist at Cedars-Sinai Medical Center in Los Angeles and EXTRACT-PE Steering Committee member, noted the data’s clinical value upon initial presentation. “From a pulmonologist’s perspective, the results of the EXTRACT-PE trial are another important dataset that help broaden the mechanical treatment options for patients with pulmonary embolism.” He went on to say that “The safety profile of the Indigo System and the low rate of bleeding events, combined with the significant reduction in RV/LV ratio seen in the EXTRACT-PE trial, can positively impact the emerging field of acute pulmonary embolism intervention.”

 

About the Indigo Aspiration System

Penumbra’s Indigo Aspiration System, launched in 2014, can be used to remove emboli and thrombi from vessels of the peripheral arterial and venous systems, and for treatment of pulmonary embolism. A minimally-invasive device, Indigo helps to enables the restoration of blood flow in such cases as acute limb ischemia and venous thrombus. The Indigo System utilizes the Penumbra ENGINE® aspiration source capable of delivering nearly pure, continuous vacuum (-29 inHg or 98.2 kPa)b to Penumbra catheters, enabling thrombus removal in vessels of various sizes. The Indigo System can be used as a first-line approach or rescue therapy for arterial and venous thrombotic events.

Lightning Intelligent Aspiration

The Indigo System with Lightning is an intelligent aspiration system powered by Penumbra ENGINE and was recently introduced in July 2020. Lightning Aspiration Tubing has dual pressure sensors for real-time blood flow monitoring. The built-in microprocessor features a proprietary thrombus removal algorithm that automatically controls a valve in the tubing to provide continuous or intermittent aspiration. This unique mechanism of action helps optimize thrombus removal procedures by differentiating between thrombus and blood. The system is designed to aspirate continuously when in thrombus and intermittently in patent flow. With Lightning, the physician only needs to place the catheter at the clot and turn on aspiration to begin thrombus extraction. When the Indigo aspiration catheter is in patent flow, Lightning is designed to automatically register a change in pressure and minimizes flow with intermittent aspiration.

Throughout each case, Lightning provides procedural feedback via audiovisual cues. Lightning’s thrombus removal algorithm is designed to initiate automatic valve clicking when it senses patent flow. With automatic valve control, Lightning may help reduce blood loss and allow the physician to focus on optimizing thrombus removal procedures.

 

Clot Detection

Newest Generation of Indigo Aspiration System

Indigo System Lightning 12

Launched in July 2020, the Indigo System Lightning 12 is the company’s newest generation aspiration system for peripheral thrombectomy. Lightning 12 combines the Indigo System CAT12 Aspiration Catheter with Lightning Intelligent Aspiration, enabling physicians to focus on optimizing thrombus removal using the system’s unique clot detection mechanism. CAT12 is a large-lumen aspiration catheter that incorporates novel lasercut hypotube-based catheter engineering to provide advanced deliverability and torqueability within the body. This combination of intelligent aspiration and large-lumen catheter engineering makes Lightning 12 Penumbra’s most advanced clot removal technology for the treatment of pulmonary embolism.

Innovation: Clot Detection Mechanism Makes for Intelligent Aspiration

FDA clearance of the PE treatment indication for Lightning 12 and Separator™12 was announced in November 2020.

Innovation: Clot Detection Mechanism Makes for Intelligent Aspiration

In addition to Lightning 12, the Indigo System also includes Lightning 8, which combines the Indigo System CAT 8 Aspiration Catheter with Lightning Intelligent Aspiration for the removal of fresh, soft emboli and thrombi from the peripheral arterial and venous systems, and for the treatment of pulmonary embolism. Lightning 12 and Lightning 8 expand the already broad offering of CAT8, CATD, CAT6, CAT5, and CAT3 and are paired with Penumbra ENGINE, the company’s proprietary continuous, mechanical vacuum aspiration pump.

Innovation: Clot Detection Mechanism Makes for Intelligent Aspiration

Footnotes

a. Trial device used was Indigo Aspiration System and catheter was limited to the Indigo System CAT™8 used in conjunction with the SEP8 on a per case basis. Lightning 12 was not available at time of trial.

b. Tests performed and data on file at Penumbra, Inc. Bench test results may not be indicative of clinical performance.

Sources

1. Sista AK, Horowitz JM, Tapson VF, et al. on behalf of EXTRACT-PE Investigators. Indigo Aspiration System for Treatment of Pulmonary Embolism: Results of the EXTRACT-PE Trial. J Am Coll Cardiol Cardiovasc Interv. Jan 13, 2021. Epublished doi: 10.1016/j.jcin.2020.09.053

2. NIH ACTIV initiative launches adaptive clinical trials of blood clotting treatments for COVID19. National Heart, Lung, and Blood Institute website. September 10, 2020. Accessed: February 4, 2021. https://www.nhlbi.nih.gov/news/2020/nih-activ-initiative-launchesadaptive-clinical-trials-blood-clotting-treatments-covid-19.

3. Benjamin, E.J. et al. on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2019 update: a report from the American Heart Association. Circulation. 2019;139:e56—e528.

4. Centers for Disease Control and Prevention. What is Venous Thromboembolism? https://www.cdc.gov/ncbddd/dvt/facts.html. Last reviewed: February 7, 2020. Accessed: January 26, 2021.

5. Desai KR. Mechanical Thrombectomy in Pulmonary Embolism [editorial] J Am Coll Cardiol Cardiovasc Interv. [Internet]. 2021 Jan 13. Epublished doi: 10.1016/j.jcin.2020.11.002. Available from https://www.jacc.org/doi/10.1016/j.jcin.2020.11.002

 

Photographs and video recording taken by and on file at Penumbra, Inc.

The clinical results presented herein are for informational purposes only, and may not be predictive for all patients. Individual results may vary depending on patient-specific attributes and other factors.

Copyright ©2021 Penumbra, Inc. All rights reserved. The Penumbra P logos, Indigo, CAT, Lightning, Penumbra ENGINE, MAX, and Separator are registered trademarks or trademarks of Penumbra, Inc. in the USA and other countries. All other trademarks are the property of their respective owners. 20260, Rev. A 02/21 USA

Risk Information

Caution: Federal (USA) law restricts these devices to sale by or on the order of a physician. Prior to use, please refer to the Instructions for Use for complete product indications, contraindications, warnings, precautions, potential adverse events, and detailed instructions for use. Please contact your local Penumbra representative for more information.

 

INDIGO Aspiration System – Indication for Use

INDIGO Aspiration Catheters and Separators:
As part of the INDIGO Aspiration System, the INDIGO Aspiration Catheters and Separators are indicated for the removal of fresh, soft emboli and thrombi from vessels of the peripheral arterial and venous systems, and for the treatment of pulmonary embolism.

INDIGO Aspiration Tubing:
As part of the INDIGO Aspiration System, the INDIGO Sterile Aspiration Tubing is indicated to connect the INDIGO Aspiration Catheters to the Penumbra Aspiration Pump.

Penumbra Aspiration Pump:
The Penumbra Aspiration Pump is indicated as a vacuum source for Penumbra Aspiration Systems.

Contraindications
Not for use in the coronaries or the neurovasculature.

Warnings
• The INDIGO Aspiration System should only be used by physicians who have received appropriate training in interventional techniques. • Do not advance, retract or use any component of the INDIGO System against resistance without careful assessment of the cause using fluoroscopy. If the cause cannot be determined, withdraw the device or system as a unit. Unrestrained torquing or forced insertion of the catheter or SEPARATOR against resistance may result in damage to the device or vessel. • Do not use the INDIGO Aspiration System with a pump other than the Penumbra Aspiration Pump. • Placing guidewire too distal in the pulmonary vasculature or excessive manipulation of aspiration/guiding catheter in the smaller, peripheral, and segmental pulmonary artery branches can result in vessel perforation.

Precautions
• The device is intended for single use only. Do not resterilize or reuse. • Do not use kinked or damaged devices. Do not use open or damaged packages. Return all damaged devices and packaging to the manufacturer/distributor. • Use prior to the “Use By” date. • Use the INDIGO Aspiration System in conjunction with fluoroscopic visualization. • Maintain a constant infusion of appropriate flush solution. • When performing aspiration, ensure that the INDIGO Aspiration Tubing is open for only the minimum time needed to remove thrombus. Excessive aspiration or failure to close the INDIGO Aspiration Tubing when aspiration is complete is not recommended. • Hemoglobin and hematocrit levels should be monitored in patients with >700 mL blood loss from the clot aspiration procedure. • The INDIGO SEPARATOR is not intended for use as a guidewire. If repositioning of the INDIGO Aspiration Catheter is necessary during the revascularization procedure, such repositioning should be performed over an appropriate guidewire using standard catheter and guidewire techniques. • Do not use automated high-pressure contrast injection equipment with the INDIGO Aspiration Catheter because it may damage the device.

Potential Adverse Events
Possible complications include, but are not limited to, the following: allergic reaction and anaphylaxis from contrast media; acute occlusion; air embolism; arrhythmia; arteriovenous fistula; cardiac injury; cardio-respiratory arrest; death; device malfunction; distal embolization; emboli; excessive blood loss; false aneurysm formation; hematoma or hemorrhage at access site; inability to completely remove thrombus; infection; hemorrhage; ischemia; kidney damage from contrast media; neurological deficits including stroke; vessel spasm, thrombosis, dissection, or perforation; intimal disruption; myocardial infarction; emergent surgery; fibrillation; hypotension; hemoptysis; respiratory failure; thromboembolic events.

 

INDIGO Aspiration System with LIGHTNING Aspiration Tubing – Indication for Use

INDIGO Aspiration Catheters and Separators:
As part of the INDIGO Aspiration System, the INDIGO Aspiration Catheters and Separators are indicated for the removal of fresh, soft emboli and thrombi from vessels of the peripheral arterial and venous systems, and for the treatment of pulmonary embolism.

INDIGO Aspiration Tubing:
As part of the INDIGO Aspiration System, the INDIGO Sterile Aspiration Tubing is indicated to connect the INDIGO Aspiration Catheters to the Penumbra Aspiration Pump.

Penumbra Aspiration Pump:
The Penumbra Aspiration Pump is indicated as a vacuum source for Penumbra Aspiration Systems.

Contraindications
There are no known contraindications.

Warnings
• Do not use the INDIGO Aspiration System with a pump other than a Penumbra Aspiration Pump. • Use of LIGHTNING Aspiration Tubing adjacent to other equipment should be avoided because it could result in improper operation. If such use is necessary, LIGHTNING Aspiration Tubing and the other equipment should be observed to verify that they are functioning properly. • Portable RF communications equipment (including peripherals such as antenna cables and external antennas) should be used no closer than 12 inches (30 cm) to any part of LIGHTNING Aspiration Tubing. Otherwise, this could result in degradation of the performance of this equipment.

Precautions
• The device is intended for single use only. Do not resterilize or reuse. • Do not use kinked or damaged devices. Do not use open or damaged packages. Return all damaged devices and packaging to the manufacturer/distributor. • Use prior to the “Use By” date. • When performing aspiration, ensure that the INDIGO Aspiration Tubing is open for only the minimum time needed to remove the thrombus. Excessive aspiration or failure to close the INDIGO Aspiration Tubing when aspiration is complete is not recommended. • Do not use in the presence of a flammable anesthetic mixture with air or nitrous oxide. • Do not use in oxygen rich environment.

Potential Adverse Events
Possible complications include, but are not limited to, the following: allergic reaction and anaphylaxis from contrast media; acute occlusion; air embolism; arrhythmia/fibrillation; arteriovenous fistula; death; device malfunction; distal embolization; emergent surgery; false aneurysm formation; hematoma, hemorrhage, or blood loss at access site; hematoma, hemorrhage, or blood loss; hypotension; inability to completely remove thrombus or control blood flow; infection; ischemia; kidney damage from contrast media; myocardial infarction; neurological deficits including stroke; respiratory failure; thromboembolic events; vascular complications (including vessel spasm, thrombosis, intimal disruption, dissection, or perforation).

 

LIGHTNING Aspiration Tubing – Indication for Use

INDIGO Aspiration Tubing
As part of the INDIGO Aspiration System, the INDIGO Sterile Aspiration Tubing is indicated to connect the INDIGO Aspiration Catheters to the Penumbra Aspiration Pump.

Contraindications
There are no known contraindications.

Warnings
• Do not use the INDIGO Aspiration System with a pump other than a Penumbra Aspiration Pump. • Use of LIGHTNING Aspiration Tubing adjacent to other equipment should be avoided because it could result in improper operation. If such use is necessary, LIGHTNING Aspiration Tubing and the other equipment should be observed to verify that they are functioning properly. • Portable RF communications equipment (including peripherals such as antenna cables and external antennas) should be used no closer than 12 inches (30 cm) to any part of LIGHTNING Aspiration Tubing. Otherwise, this could result in degradation of the performance of this equipment.

Precautions
• The device is intended for single use only. Do not resterilize or reuse. • Do not use kinked or damaged devices. Do not use open or damaged packages. Return all damaged devices and packaging to the manufacturer/distributor. • Use prior to the “Use By” date. • When performing aspiration, ensure that the INDIGO Aspiration Tubing is open for only the minimum time needed to remove the thrombus. Excessive aspiration or failure to close the INDIGO Aspiration Tubing when aspiration is complete is not recommended. • Do not use in the presence of a flammable anesthetic mixture with air or nitrous oxide. • Do not use in oxygen rich environment.

Potential Adverse Events
Possible complications include, but are not limited to, the following: allergic reaction and anaphylaxis from contrast media; acute occlusion; air embolism; arrhythmia/fibrillation; arteriovenous fistula; death; device malfunction; distal embolization; emergent surgery; false aneurysm formation; hematoma, hemorrhage, or blood loss at access site; hematoma, hemorrhage, or blood loss; hypotension; inability to completely remove thrombus or control blood flow; infection; ischemia; kidney damage from contrast media; myocardial infarction; neurological deficits including stroke; respiratory failure; thromboembolic events; vascular complications (including vessel spasm, thrombosis, intimal disruption, dissection, or perforation).

 

PENUMBRA ENGINE — Indication for Use
The PENUMBRA ENGINE is indicated as a vacuum source for Penumbra Aspiration Systems.

Contraindications
There are no contraindications.

Warnings/Precautions
•The canister is intended for single use only. Do not reuse. Reuse may result in canister cracking or vacuum filter blockages, which may result in the inability to aspirate.

•Do not block bottom air vents. Unit may overheat and shut off or fail to restart if run for extended periods of time without airflow.

•To avoid the risk of electrical shock, this equipment must only be connected to a supply mains with protective earth.

•Do not position the PENUMBRA ENGINE so that it is difficult to remove the power cord. The means of mains disconnect is to remove the power cord.

•Only use replacement fuse with correct rating (see Table 1 for fuse rating).

•Remove and service the PENUMBRA ENGINE if liquids or solids have been drawn into the PENUMBRA ENGINE.

•Do not use in the presence of a flammable anesthetic mixture with air or nitrous oxide.

•Do not use in an oxygen rich environment.

•To prevent fire or shock hazard, use a replacement power cord of equal rating.

•Do not re-infuse blood or fluid from the canister back into the patient.

•Do not use petroleum based compounds, acids, caustics, or chlorinated solvents to clean or lubricate any parts. It will reduce the service life of the PENUMBRA ENGINE. Use only water-based solvents for cleaning.

•Use of this equipment adjacent to or stacked with other equipment should be avoided because it could result in improper operation. If such use is necessary, this equipment and the other equipment should be observed to verify that they are operating normally.

•Portable RF communications equipment (including peripherals such as antenna cables and external antennas) should be used no closer than 12 inches (30cm) to any part of the PENUMBRA ENGINE. Otherwise, this could result in degradation of the performance of this equipment.

•Common emitters (such as RFID emitters, security systems, diathermy equipment, and portable transmitters) should not be used in close proximity to the PENUMBRA ENGINE as they can interfere with and result in degradation of the performance of the equipment.

•Equipment is not safe for MR use.

•No modification of this equipment is allowed.

 

Penumbra Pump MAX – Indication for Use
The Penumbra Pump MAX is indicated as a vacuum source for the Penumbra Aspiration Systems.

Contraindications
There are no contraindications.

Warnings/Precautions
• The canister/tubing is intended for single use only. Do not reuse. Reuse may result in canister
cracking or tubing blockages, which may result in the inability to aspirate. • Do not block bottom
or back air vents. Unit may overheat and shut off or fail to restart if run for extended periods of
time without airflow. • To avoid risk of electric shock, this equipment must only be connected to
a supply mains with protective earth. • Do not position the pump so that it is difficult to operate
the power cord disconnection device. • Remove and service the pump if liquids or solids have
been drawn into the vacuum pump. • Do not use in the presence of a flammable anaesthetic
mixture with air or nitrous oxide. • Do not use in oxygen rich environment. • To prevent fire or
shock hazard, use replacement fuses of equal size and rating. • To prevent fire or shock hazard,
use a replacement power cord of equal rating. • Do not re-infuse blood or fluid from the canister
back into patient. • Do not use petroleum base compounds, acids, caustics, or chlorinated
solvents to clean or lubricate any parts. It will reduce the service life of the pump. Use only
water-base solvents for cleaning. • Federal (USA) law restricts this device to sale by or on the
order of a physician. • No modification of this equipment is allowed.