September 3, 2020 - Abbott announced today the LIFE-BTK clinical trial to evaluate the safety and efficacy of the company's new Esprit BTK everolimus-eluting absorbable stent system. This is the first investigational device waiver (IDE) trial in the United States designed to evaluate a fully bioabsorbable stent for the treatment of patients with advanced peripheral arterial disease (PAD) with below-the-knee arterial occlusion or critical limb ischemia (CLI). New York-Presbyterian/Columbia University Irving Medical Center vascular surgeon Danielle Bajakian, MD, enrolled the first patient.

"Too many people suffer from peripheral arterial disease, and this new drug-eluting absorbable stent offers meaningful improvements in how to treat this disease," said Nick West, MD, vice president for medical affairs, and Chief Medical Officer of Abbott's Vascular Business. "Patients treated with balloon angioplasty often require repeat surgery on the treated artery, so drug-eluting absorbable stents are ideal for providing mechanical support to the vessel, reducing the chance of restenosis, which then fades over time ."

In people with CLI, blocked blood vessels reduce blood flow to the lower extremities, which can lead to severe pain, difficult-to-heal wounds, and in some cases, amputation. Globally, more than 200 million people suffer from PAD, disproportionately affecting areas with insufficient medical capacity. To make matters worse, up to 40% of CLI patients currently undergo amputation, and eliminating disparities in healthcare could prevent many amputations.

Currently, the standard of care for CLI is balloon angioplasty, which relies on a catheter to deliver a small balloon to the site of the blockage, opening the vessel and restoring blood flow. However, balloon angioplasty alone has poor short- and long-term results for occlusion, and in many cases the vessel becomes re-occluded, requiring additional treatment.

There are currently no drug-eluting stents (DES), drug-coated balloons (DCB), or bare-metal stents (BMS) approved for use below the knee (BTK) in the United States. Because treatment options for BTK are limited, new treatment options are needed. The U.S. Food and Drug Administration (FDA) granted Esprit BTK Breakthrough Device Designation, which simplifies the timeline for review and premarket approval.

Unlike traditional metal stents, Abbott's Esprit BTK System is not a permanent implant; it provides effective support for the artery immediately after balloon angioplasty, preventing the vessel from collapsing and reclosing. Once implanted, stents can deliver drugs that promote healing and keep arteries open for months. Over time, the stent will naturally absorb into the body like absorbable sutures, eventually leaving only a healed artery. Abbott is a pioneer in bioresorbable stents. A meta-analysis of long-term clinical data from randomized trials suggests that bioresorbable stents may be an acceptable alternative to metallic DES for many patients with coronary artery disease.

Ramon Varcoe, PhD, MBBS MS FRACS, University of New South Wales, Sydney, Australia, and one of the trial's principal investigators, said: "After five years of feasibility studies, the results of the evaluation show that absorbable stents have great potential to become the treatment of choice for patients with CLI. This technology offers the best of both worlds. The stent provides a robust stent structure and delivers anti-proliferative drugs that then disappear and are not a hindrance to future interventions, procedures or imaging."

Once enrollment is complete, the LIFE-BTK trial will evaluate the Esprit BTK absorbable stent in 225 patients at centers around the world. The study is the first of its kind and an evolution of previous studies of absorbable technology in the treatment of diseased blood vessels and arterial blockages.

LIFE-BTK test related information

The LIFE-BTK trial is the first fully dissolvable stent IDE trial in the United States to evaluate critical limb ischemia in patients with advanced peripheral arterial disease (PAD). So far, the trial has been launched in Australia, Japan, New Zealand, Singapore and the United States.

The LIFE-BTK trial is a prospective randomized controlled clinical trial comparing Esprit BTK and percutaneous transluminal angioplasty (PTA) in the treatment of CLI. The purpose of this study was to evaluate the safety and efficacy in patients with CLI.

The trial will be led by principal investigators including Brian DeRubertis, MD (UCLA Vascular Surgeon, UCLA), Sahil Parikh, MD (Interventional Cardiologist, New York-Presbyterian/Columbia University Irving Medical Center, Abbott Vascular Medicine) Advisory Board Member) and Ramon Varcoe MBBS MS FRACS PhD (University of New South Wales, Sydney, Australia).

Interest in bioresorbable stents has revived three years after coronary resorbable stent technology was withdrawn from the market

5-6 years ago, with the development of coronary stents, the enthusiasm for bioabsorbable stent technology was growing. In 2015, the FDA approved the market of absorbable stents, namely Abbott's bioabsorbable vascular stent (BVS). However, data from the ABSORBIII trial led directly to the withdrawal of the first commercially available bioresorbable stent on September 14, 2017. This has raised questions about the future of the technology.

The sales of this absorbable stent are not good, but according to the test data of several absorbable stents, its performance is good compared with the mainstream Xience everolimus-eluting metal stent. However, a slight discrepancy in the data would negate any long-term benefit the stent might provide. Experts involved in the trial said the use of absorbable stents is very low, estimated at less than 5% in the United States. This has led other device makers, such as Boston Scientific, to shelve their own BVS studies. In 2018, Abbott said it would continue the BVS study and hope to launch a prospective trial of an improved absorbable stent for commercial applications, which is what Esprit BTK is currently doing.

About Esprit BTK Bioabsorbable Stent System

The Esprit BTK system consists of a thin 99-micron stent system made of levorotatory polylactic acid (PLLA), a semi-crystalline bioabsorbable polymer that resists vasoconstriction and provides a platform for drug delivery. The scaffolds were uniformly coated with racemic polylactic acid (PDLLA) and the cytostatic drug everolimus. PDLLA is an amorphous bioabsorbable polymer coating for controlled release of drugs. Everolimus is a drug that inhibits cell proliferation, which reduces the growth of endothelial tissue in the affected area and avoids blockage of blood vessels.

About critical limb ischemia

Critical limb ischemia is a severe form of PAD characterized by chronic pain, even at rest, as well as ulceration and gangrene (tissue necrosis) caused by chronic insufficiency of blood supply to the lower extremities. The most common endovascular treatment for the arteries below the knee is balloon angioplasty, which uses a catheter-guided balloon to dilate the vessel at stenoses and occlusions. Vascular bypass surgery is also possible for some patients. If left untreated, the disease can eventually lead to amputation.

  references:

1. Fowkes et al. Comparison of global estimates of peripheral arterial disease prevalence and risk factors in 2000 and 2010: a systematic review and analysis. The Lancet 2013;382:1329-40

2. https://www.amptee-coalition.org/resources/limb-loss-statistics/

3. Stone et al. Time-varying outcomes of absorbable bioresorbable vascular stents at 5-year follow-up: a systematic integrative analysis and pooled individual patient data study JAMA Cardiol 2019 Dec 1;4(12):1261-1269. doi: 10.1001/jamacardio.2019.4101.

  Expert Reviews

Xiong Jiang, Chief Physician, Associate Professor and Master Supervisor of Cardiovascular Surgery in the First Medical Center of PLA General Hospital. The research direction is to construct a clinical diagnosis and treatment system for aortic dissection based on hemodynamics. As the first person in charge, he has won 1 key research and development project of the Ministry of Science and Technology, 2 National Natural Science Foundation of China, 2 provincial and ministerial level funds, etc. A total of 26 SCI papers have been published, with a total impact factor of 78 points, the highest impact factor of a single paper is 8.5 points (Top of the first district of the Chinese Academy of Sciences), and the highest citation rate of a single paper is 71 times.

For the development of treatment technology for inferior popliteal artery occlusion, the earliest use of percutaneous transluminal angioplasty (PTA) was to use a bare balloon to expand the lesion site and open the occlusion site. The clinical effect of this technology was 6 months. The patency rates at 12 months and 36 months were 65.0%, 58.1%, and 48.6%, respectively. The introduction of bare metal stent implantation (BMS), although BMS will reduce the acute rebound and dissection of the lesion, the clinical results show that BMS and PTA have no obvious advantages in vascular patency rate. In recent years, there have been many clinical results showing that drug-eluting stent implantation (DES) has obvious advantages over BMS and PTA in terms of vascular patency rate, this is because the anti-proliferative drugs on the stent play a role, and its one-year patency. The rate is about 78%-85%, and it is suitable for lesions with a length of 17mm-31mm. More and more clinical trials show that DES is the optimal choice for the treatment of peripheral short lesions and atherosclerotic lesions. Bioabsorbable stent (BRS) first appeared in the inferior knee artery in 2004, represented by Biotronik's Magmaris stent. The 3-month clinical patency rate was as high as 90%, but the 6-month patency rate was only 31.8%. Due to differences between humans and animals, magnesium alloy stents degrade faster than expected, leading to stent collapse and restenosis. Abbott launched a clinical trial called "ABSORB BTK" in 2011, using a polylactic acid stent, but the trial was terminated after too few patients were enrolled (mainly because the stent was too short to make enrollment difficult). Two subsequent clinical trials (NOC02793349 and NOC02043795) were subsequently initiated in 2013 and 2016, respectively, by allowing overlapping stents, with 24 and 33 patients each, with 1-year patency rates of 87% and 96%. %. It is proved that the application of the absorbable polylactic acid stent in the subknee artery is feasible, and it also brings hope to the application of the bioabsorbable stent in the treatment of the subknee artery disease.

The LIFE-BTK clinical trial restarted by Abbott this time uses a semi-crystalline bioabsorbable polymer poly-L-lactide (PLLA) as the matrix, and the drug contained in it is everolimus. The advantages of this absorbable stent include: PDLLA is an amorphous bioabsorbable polymer coating for controlled drug release; PDLLA is naturally absorbed into the body like dissolving sutures; The problem of increased long-term mortality in the paclitaxel class.

The domestic Yuanxin Technology (Shenzhen) Co., Ltd. is currently conducting clinical trials of subpopliteal absorbable iron-based stents in Beijing 301 Hospital. The matrix used is pure iron (Fe) infiltrated with 0.05% N, and the drug contained is sirolimus. manage. The advantages of this absorbable stent include: the unique nitriding process enables this absorbable stent to maintain sufficient supporting force while the stent wall thickness can be reduced to 60μm, the stent has a variety of specifications, the longest can be up to 118mm, specifically for the subpopliteal Diffuse disease development; the stent is loaded with polylactic acid (PLLA) to control drug release, and the degradation cycle of the entire stent is 16-24 months. It is worth mentioning that the iron-based absorbable stent has been clinically followed for up to 2 years in the coronary artery outside the monsoon. The results preliminarily prove the safety and effectiveness of the iron-based absorbable stent. completely degraded in the vein.