Drug-coated balloon simulation and optimization system for the improved treatment of peripheral artery disease

Project Information

DECODE

Grant agreement ID: 956470

DOI

10.3030/956470

Project closed

EC signature date 20 August 2020

Start date 1 January 2021

End date 30 June 2025

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 3 612 339,82

EU contribution

€ 3 612 339,82

Coordinated by

PANEPISTIMIO IOANNINON
Greece

Periodic Reporting for period 2 - DECODE (Drug-coated balloon simulation and optimization system for the improved treatment of peripheral artery disease)

Reporting period: 2023-01-01 to 2025-06-30

Summary of the context and overall objectives of the project

DECODE has focused on the training of young scientists on the use of drug-eluting devices to combat the burden of peripheral artery disease (PAD). PAD affects 202 million patients worldwide and may cause disabling intermittent claudication and critical limb ischemia (CLI). The global prevalence of PAD has been increased especially in low-income and middle-income countries, exceeding 20% in persons >70 years old. The majority of patients with CLI have distal arterial disease located mainly below the knee. The endovascular treatment landscape encompasses a broad range of interventions, with each option having advantages and disadvantages. Bare metal stents (BMS) usually yield better outcomes compared to plain balloon angioplasty alone as they stabilize any dissection and prevent rapid elastic recoil. However, they increase local inflammation, leading to neointimal hyperplasia formation and in-stent restenosis. Also, they are associated with increased fracture rate, especially in the femoropopliteal segment.
Drug-coated balloons (DCB) and drug eluting stents (DES) have been developed to address the aforementioned disadvantages. The advantage of using paclitaxel-coated balloons is the ability to deliver the necessary drug to the affected areas without a permanent vascular prosthesis. Regarding femoropopliteal lesions, DCBs have been found to be superior than plain balloons as far as clinical improvement, target lesion revascularization and restenosis are concerned. Compared to DES, results are promising showing equal efficiency with lower cost even for long femoropopliteal lesions although data are still limited.
The overall objectives of DECODE were to provide:
-Excellent scientific training on the biomechanical properties of DCBs, integrating clinical knowledge with technological skills on materials science, engineering and numerical modelling to generate innovative insights triggering the improved understanding and treatment of PAD.
-Excellent complementary skills in personal and career development, as well as ongoing support and business training required to extend beyond scientific research.
-Exposure to both academic and non-academic environments, required to build bridges between researchers and companies, between theory and practice, which is challenging for young researchers and necessary for businesses.
-An advising network to ensure that Early Stage Reasearchers (ESRs) will become well-rounded scientists, as well as well-rounded persons. This multidisciplinary training programme has been implemented by leading universities, clinical centers and non-academic partners from Europe and US.
Overall, no delays and deviations have appeared and the objectives have been successfully addressed within RP1 and RP2.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

-All the deliverables of RP1 and RP2 have been submitted on time.
-All the training activities have been performed, as described in the DoA (Table 1.2 b) and the secondments have been performed.
-Different versions of the ESRs' personal career development plans have been developed and integrated in the deliverables of WP2 (D2.1 D2.2 D2.3).
-More than 60 Journal and Conference papers have been published.
-Concerning the in-vitro study in WP3, the findings have significant clinical implications, as they inform the development of safer, more effective DCB technologies by highlighting critical failure points and guiding the design of delivery methods that minimize off-target drug loss and improve therapeutic precision. The DECODE animal study: i) established an injury protocol that presents a clinically relevant porcine model for DCB application and collected imaging data for vessel reconstruction and coating transfer,ii) with this model it could be shown that tracking is the main driver of premature drug-loss with Paclitaxel-coated balloons, iii) showed, that (low pressure) frictional contact between DCB coating and arterial wall can efficiently drive coating transfer to targeted and non-targeted tissue.
-WP4 presented computational models at different scales:
i) Micro/nano scale computational models were developed to: i) reproduce and interpret the experimental outcomes observed in laboratory tests and obtain useful data, ii) design the experimental setups and protocols for novel in vitro/ex vivo tests performed at mesoscale on DCBs, iii) to predict some in vivo behavior of interest for DCBs design.
ii) Macro/meso scale computational models were developed to reproduce the complex mechanical and fluidic interactions between the DCB and the arterial environment, shedding light on the factors influencing effective drug delivery and the device’s clinical performance.
-In WP5, the main outcome was the development, deployment, and evaluation of the DECODE Cloud Platform, which is a modular, open-source, cloud-native system designed for the non-invasive diagnosis and treatment planning of PAD.
-The website and social media were updated at a regular basis.
-The final version of the exploitation plan and IP issues have been prepared (D1.6). Six Key Exploitable Results have been defined.
-The ethical issues were addressed (WP6 submitted deliverables).

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Until the end of the project, the consortium managed to achieve the following:

- New vessel segmentation algorithm for PAD with accuracy higher than state of the art.
- New algorithm for calcification detection.
- New method of holographic measurements with automatic path planing in the vessels.
- New algorithm for centreline generation with realtime implmentation that takes into account the bifurcation problem.
- Optimized/New drug eluting coatings for angioplasty balloons.
- Improved drug transfer to vessel wall and drug delivery to intended cells.
- Combination of clinical knowledge combined with research expertise to test and refine DCB deployment for PAD.
- Analysis of drug transfer and downstream embolisation in human size vascular system (swine).
- Computational models for simulating various aspects of DCBs: i) simulation of the DCB angioplasty, ii) simulation of the interaction between the drug-coating and balloon membrane upon deformation, iii) simulation of the drug-coating transfer to the arterial wall during the surgical procedure.
- Novel experimental set-ups: i) to characterize the mechanical stability of the drug-coating on the polymer substrates, ii) to characterize the interaction between the drug-coating and the arterial wall and, iii) to have an ex-vivo system mimicking the in vivo environment and effectively test DCBs.
- New platform able to enhance clinical decision making incorporating various computational tools.

The potential impacts are:

- Industrial development of new devices or improvement of the existing ones.
- Improved clinical strategy and patient outcome with new devices and software.
- The use of computational models could have an economic impact as they can support the production of optimized drug-coated devices, thus potentially allowing saving drug and associated high costs.
- Reduction of chance for a secondary intervention, which is more frequently occurring in non-effective drug treatments.
- Optimisation of DCB technology and deployment technique (with impact from an interventionists point of view).
- Understanding the extent of downstream embolisation risk and establishment of research procedures to analyse downstream embolisation.
- Creation of robust and reliable experimental set up and analysis pipeline to study drug eluted devices for PAD.

DECODE Cloud Platform Home Interface - Access to Peripheral Artery Disease Analysis Tools.