Балонные катетеры с лекарственным покрытием

[pokrovka]

Уважаемые господа, используете ли вы этот "девайс" в своей практике? Если да то в каких случаях? какие именно предпочитаете?? Как относитесь к "Диору"? Существуют ли официальные рекомендации по их использованию? Каков опыт?

[Abugov]

Наступаете на больное. Как только доберусь до полноценной клавиатуры (сейчас - мобильный девайся) разражусь соображениями. Ждем мнений от остальных.

[angio]

Наши больница вступила в исследование Valentine, используем крайне мало и не слишком охотно - ISR only. Отдаленных результатов пока нет. Есть одна пациентка с повторным рестенозом 90%Д через 3 месяца, в итоге поставили DES в BMS.

Предлагаю в этой же теме обсудить биоинжинерные стенты с ускоренной эндотелизацией.

[DVS]

Опыт ограничился 5 баллонами, использованных при рестенозах BMS, и то "интереса ради". Дело было 3-4 месяца назад, пока что ни один из пациентов опробовавших на себе сию чудную технологию не вернулся, но это не показатель =)))

[FRSM]

Drug-Eluting Balloon Catheters
EmailWritten by padraic526 on Mar-18-09 12:10am
From: mediligence.com
[Through the course of researching and analyzing the global coronary stent market for an upcoming report, we have compiled data on the ancillary market of drug-eluting balloons, which we synopsize below.]

Drug-Eluting Balloons

A handful of companies are developing drug-coated balloon catheters as an alternative to balloon angioplasty and stenting and for those who would not benefit from PCI, such as those in whom antiplatelet therapy is neither recommended nor desired. Companies developing drug-coated balloon catheters include: EuroCor/Opto Circuits, Lutonix, Possis Medical, B. Braun Melsungen, Aachen Resonance, Genesis Technologies, and DSM Biomedical (in partnership with Caliber Therapeutics).

Drug-coated balloons were first investigated in the 1990s, but were not pursued at that time due to difficulties in transferring the drug from the balloon into the tissue quickly enough. In 2006, Lixiao Wang (formerly at EV3 and SciMed, now chief technology officer at early stage company Lutonix, Inc.) developed an additive that allows the tissue to quickly absorb the drug.

The concept behind the technology is based on the assumption that delivering a rapid release of drugs into the arterial tissue is more effective than the gradual release of drugs, as seen with drug-eluting stents. Another side benefit of the technology would be significant cost-savings. Angioplasty balloons currently used typically cost roughly $400 each.

Lutonix Inc. was founded in 2007 to develop and commercialize drug-coated angioplasty technology for treating coronary and peripheral artery stenosis caused by atherosclerosis. The company received a $20 million Series B financing in October 2008 and hopes to start human trials in 2009 and U.S. trials in 2010. Lutonix officials hope to see an FDA approval granted by 2014.

A similar additive technology was developed by German scientists, a technology that is now owned by Bayer. When Bayer AG (and its Medrad affiliate) acquired Possis Medical in March 2008, the company gained not only the Possis diagnostic imaging business, but also gained the company’s paclitaxel-coated angioplasty balloon catheter. The device is mostly being held under wraps, but early evaluations have shown the drug-coated balloon catheter to have encouraging results in peripheral applications. Findings published in the New England Journal of Medicine in November 2006 suggested that the technology could duplicate, if not outperform, drug-coated stents in preventing restenosis. The scientists reported lower incidences of adverse events and recurrent in-stent restenosis related to the drug-coated balloons.

Researchers led by Dr. Gunnar Tepe of Eberhard-Karks University in Tubingen, Germany, coated standard angioplasty balloons with paclitaxel and tested it in 48 patients, as well as in another 52 patients who were injected with a high-dose of paclitaxel mixed with contrast medium. Another 54 patients did not receive paclitaxel in any form.

At six months post-op, 37% of the non-paclitaxel patients and 29% of the paclitaxel/contrast medium patients required additional surgery, compared to 4% of patients who were treated with the drug-coated balloon. At two years post-op, 15% treated with the coated balloon required additional surgery compared to 40% of those who received the paclitaxel/contrast medium and 52% of those who did not receive paclitaxel.

B. Braun Melsungen’s SeQuent Please drug-eluting balloon catheter features a matrix coating that is fully bioabsorbable and polymer-free. The device is being evaluated in the ongoing PEPCAD trials in Germany. In PEPCAD I (the first study to investigate the use of drug-eluting balloons in native lesions), the SeQuent Please patients (n=120) showed a 5.5% binary restenosis rate and 6.1% MACE after six months. The researchers noted that previously published rates for DES in small vessel disease were 31.2% restenosis and 18.9% MACE. In the ongoing PEPCAD II trial, SeQuent Please is being compared to another manufacturer’s DES in 131 patients.

B. Braun’s SeQuent Please coated balloon is based on the PaccoCath technology developed by Bavaria Medizin Technologie GmbH. PaccoCath benefits from a unique matrix of paclitaxel and a hydrophilic spacer on the surface of the balloon, creating a large contact surface area between the lipophilic drug and the vessel wall as well as high bioavailability of paclitaxel at the target site for rapid drug absorption by the vessel wall. This allows uniform and complete application of the drug after the first balloon inflation.

German company EuroCor, a subsidiary of Opto Circuits (India), has developed the DIOR (Dilation of Restenosis) paclitaxel-eluting balloon catheter. DIOR is designed for treatment of coronary in-stent restenosis, bifurcated coronary artery lesions, small diameter coronary arteries and coronary stenting in de novo lesions using bare metal stents. The company notes that the greatest benefits are achieved with three months of antiplatelet therapy. In addition, previously stented patients treated with DIOR remain accessible to reintervention if needed without restricting the chance of a successful repeated treatment. EuroCor claims that the drug delivered by DIOR is more evenly distributed to the vessel surface if compared with the drug distribution by stent struts. DIOR is treated like a typical PTCA catheter, is inflated to the lesion site up to 60 seconds for full drug release, and may be inflated several times. A first inflation of 20 seconds leads to 35% drug release; a second inflation of 20 seconds releases another 35% of paclitaxel. The DIOR device has received a CE Mark and was launched in February 2007.

DSM Biomedical and Caliber Therapeutics formed a partnership in September 2008 to develop a drug-delivery balloon catheter to treat atherosclerosis. DSM is contributing to the partnership its polymer-based drug delivery technology while Caliber Therapeutics is contributing its balloon catheter technology. In March 2009, DSM Biomedical obtained a worldwide, exclusive license from MediVas for a polymer-based drug and biologics delivery system for use in developing products for ophthalmic, cardiovascular, musculoskeletal and general pain relief applications.

Aachen Resonance GmbH makes the Elutax paclitaxel-eluting balloon for coronary arteries (de novo, small vessels, in-stent restenosis) and small vessels below the knee. The structural coating of Elutax is such that the drug is encased on the surface of the balloon and 20% of the total drug is released from the balloon after each inflation. In January 2009, Aachen Resonance announced that Biotronik would distribute Elutax in Switzerland, Belgium, the Netherlands, Luxembourg, England, Ireland, and italy.

Genesis Technologies, LLC, is developing its DESA (Drug-Eluting Scoring Angioplasty) technology that simultaneously creates microfractures in the stenosis and allows drugs to be delivered. DESA has a stent-like structure wrapped around an angioplasty balloon that simultaneously creates microfractures in the stenosis and allows drugs to be delivered. The devices uses an older tubular (nitinol) mesh braid that should allow costs for the device to be kept below that of competitive cutting balloons. According to Genesis, the drug coating on the balloon and/or mesh braid will cover more area than with stents and the drug on the braid will be depositied into microfractures or crevasses adjacent to the vessel wall. Once approved, Genesis plans to market DESA to all vascular interventionalists (cardiologists, interventional radiologists, and nephrologists). DESA has yet to enter human trials.

[FRSM]

В настояшее время позиция UK специалиcтов отражена:

From its inception, DEB technology sparked widespread interest from both interventional cardiologists and interventional radiologists seeking improvements in procedural success and a reduction in lesion restenosis rates. Although the most promising applications for the technology appear to be niche, especially for coronary applications, it is highly feasible that utilisation could easily spread with DEB technologies becoming a mainstream tool in the interventionalist’s repertoire, particularly for the treatment of PAD.
Indeed, its potential is highlighted by the number of companies known to be competing in this area, ranging from leading global players to small, highly specialised companies. Currently, only a handful of companies have gained market approval for their products but, with the level of pre-clinical and clinical activity reported here, many more can be expected to enter the market in the near future.
Although the technology appears to hold such promise, there is still a strong need for further clinical evidence of each product’s capability, efficacy, and safety. The criteria for gaining market acceptance must be clear as the DEB holds much promise for the treatment of life-threatening vascular disease. It is imperative to allow this technology the potential for adoption by having safe and efficacious products developed within a fairly regulated environment.

Company
Trial activity
Decelopment/launch staus
Aachen Resonance GmbH
(distributed by Biotronik AG in UK,
Switzerland, Benelux, Italy and Ireland).
Trial data submitted based on DEBIUT trial
EU launch with CE approval
B. Braun Melsungen AG
PEPCAD I and PEPCAD II trials completed assessing treatment of coronary de novo lesions and in-stent restenosis. Further trials underway
Initial launch in Malaysia.
CE application filed
Bayer AG (MEDRAD, Inc.)
Pre-clinical. Plans for clinical testing outside of the US for coronary applications
Late stage development
Caliber Therapeutics, Inc.
Clinical trial initiated to assess efficacy in peripheral applications
Early stage development
Cook Group, Inc.
Clinical trials initiated to assess efficacy in coronary applications
Late stage development
Eurocor AG
Pre-clinical testing undertaken. Clinical trial planned in 2010 to assess efficacy in peripheral applications (2nd generation device)
EU launch with CE approval
Invatec s.r.l.
Efficacy tested in porcine model. Clinical trial activity planned for both coronary and peripheral applications
EU launch with CE approval
Lutonix, Inc.
Pre-clinical testing undertaken
Early stage development

[oldangio]

Скажите? разрешение на применение таких баллонов в России имеется или наши больные будут вместо свинок как подопытные за свои деньги.

[Abugov]

В момент контакта с большой клавиатуой, творческий порыв был на нуле, попробую с маленькой.
Как известно, основными причинами рестеноза при БКА являются: организация пристеночного тромба, эластическое спадение просвета, пролиферация интимы. Первая причина исключается антикоагулянтами и антиагрегантами, вторая - стентом, третья - лекарственным покрытием. Так что, использование DEB в de novo поражениях вглядит сомнительным, т.к. Не исключается основной механизм рестенозирования - рекойл.
Лекарственное вещество, доставляемое баллоном, высвобождается "быстрым" способом. В то время как мы знаем из ранних исследований DES именно медленное высвобождение обеспечивает реальную действенность покрытых стентов. Так что, я не очень понимаю, каким образом DEB будут работать и при instent стенозах.
Имеющиеся литературные сведения, в данный момент весьма противоречивы.
Лично я, по крайней мере в настоящее время, эти баллоны не использую

[Maltsev]

Согласен с Сергеем Александровичем относительно механизма рестеноза после банальной PTCA. Но, все же, относительно рестенозов внутри стентов кое-какой эвиденс имеется: исследования PACCOCATH ISR I/II и PEPCAD. И с теоретической точки зрения, непродолжительная экспозиция к паклитакселу вроде как должна быть компенсирована трехкратным увеличением удельной дозы.

[Изображения доступны только зарегистрированным пользователям]

[Maltsev]

Хотя, конечно, DES при имплантации в рестеноз внутри BMS несколько более эффективны, по сравнению с DEB.

Но, как я понимаю, никто не хочет заменить DEB'ами DES'ы. DEB'ы должны использоваться там, где эффективность применения DES может не перевесить связвнные с этим сложности и риски.

Одним словом, should be investigated.

[Maltsev]

PEPCAD-2 ISR drug-coated balloon study now published
June 2, 2009 | Michael O'Riordan

Frankfurt, Germany - Treatment of in-stent restenosis using a balloon coated from end to end with paclitaxel is at least as efficacious as the Taxus (Boston Scientific) paclitaxel-eluting stent, according to the results of a new study [1].

"Compared with the drug-eluting stent, the drug-coated balloon induced significantly less late lumen loss and improved event-free survival," write lead investigator Dr Martin Unverdorben (University of Frankfurt, Frankfurt am Main, Germany) and colleagues in the June 1, 2009 issue of Circulation. "The benefit was observed although clopidogrel administration was shortened to three months."

The study, known as the Paclitaxel-Eluting PTCA-Balloon Catheter in Coronary Artery Disease-2 In-Stent Restenosis (PEPCAD-2 ISR) trial, was previously presented at the American College of Cardiology 2008 Scientific Sessions/i2 Summit-SCAI Annual Meeting and reported by heartwire at that time.

Briefly, 131 patients were randomized to treatment with Taxus or the SeQuent-Please balloon catheter. After six months, the drug-coated balloon cut late lumen loss in half compared with the traditional paclitaxel-coated stent. In the intention-to-treat (ITT) analysis, however, the binary restenosis rate wasn't significantly lower with the investigational balloon catheter. Rates of major adverse cardiac events were significantly lower with the drug-coated balloon, a difference driven primarily by reduced rates of target lesion revascularization.

"If future results confirm it," Unverdorben told heartwire last year, "this balloon has clear advantages over stenting. It's potentially cheaper and is associated with a shorter [duration of] clopidogrel therapy, which would increase safety."

--------
Небольшая ремарка: Как известно, сиролимус-элюирующие стенты показали более высокую эффективность в профилактике рецидивного рестеноза по сравнению с паклитаксел-элюирующими.

[Consul]

Полностью согласен с доктором Мальцевым. безусловно такие баллоны займут свою нишу, хотя бы даже для пациентов с рестенозом BMS, которым нежелателен длительный прием двойной антиагрегантной терапии.

[Maltsev]

Справедливости ради необходимо отметить, что приведенные мною исследования включали небольшое количество пациентов (108 в PACCOCATH I/II и 131 в PEPCAD-2 ISR) и их доказательная сила не очень велика.

[Abugov]

Сообщение от Consul

Полностью согласен с доктором Мальцевым. безусловно такие баллоны займут свою нишу, хотя бы даже для пациентов с рестенозом BMS, которым нежелателен длительный прием двойной антиагрегантной терапии.

Возможно, хотя слово "безусловно" я бы употреблял с осторожностью.

[Gorgadze]

Здравствуйте!
Однозначного мнения по поводу баллонов с лекарственным покрытием у меня пока нет, как всегда есть свои плюсы и минусы...
Выше уже говорили об результатах исследований PEPCAD I и II, результаты PICCOLETO в свою очередь многих разочаровали.
В настоящее время я работаю (стажируюсь) в Hospital Clinico San Carlos, в Мадриде, это государственное учреждение, что означает хорошее финансирование и широкий спектр всего чего только пожелает Hemodinamist (так называются интервенционные кардиологи), я это к тому, что у нас есть DEB, но на сегодняшний день мы их используем в основном только для больных которые входят в исследование RIBS IV-V (это исследование по изучению тактики лечения рестенозов, которую ведёт Dr.Fernando Alfonso).
И ещё, если позволите, на EuroPCR 2010, знаменитая профессор Virmani на вопрос о DEB давала однозначно негативный ответ, исходя из крайней токсичности Paclitaxel (что конечно распространяется и на DES, но это отдельный разговор)...
Я согласно с выше высказанным мнением, и думаю что DEB найдут свою нишу, например в лечении больных которым противопоказана длительная двойная антиагрегантная терапия, или же в случаях с артериями мелкого калибра... но я также думаю что это уже будут DEB следующего поколения...