Pilot Study of the α Prototype NIMBLE System: Feasibility, Safety, and Initial Performance in Non-Invasive Detection of Coronary In-Stent Restenosis

The NIMBLE-I study is a prospective, single-center, single-arm pilot clinical trial designed to assess the feasibility, safety, usability, and preliminary diagnostic performance of the NIMBLE prototype system. This study represents a significant step forward in the development of non-invasive tools for the detection of complications associated with coronary stents. It is sponsored by NIMBLE Diagnostics and takes place at the Hospital Germans Trias i Pujol in Badalona, Spain, under the leadership of Dr. Oriol Rodríguez Leor, an expert in interventional cardiology.

The rationale behind this study lies in the persistent clinical challenge of in-stent restenosis (ISR)-the re-narrowing of a coronary artery segment within a previously implanted stent. ISR continues to affect 5-10% of all percutaneous coronary intervention (PCI) cases despite advances in stent design and pharmacological therapy. Typically, ISR is diagnosed through invasive procedures such as coronary angiography or intravascular imaging (e.g., IVUS or OCT), which involve patient risk, high cost, and hospital-based infrastructure. The NIMBLE system, which employs microwave interferometry (MWI), offers a novel, non-invasive, and non-ionizing approach aimed at detecting tissue-level changes and structural anomalies suggestive of ISR. The system functions through external thoracic placement of signal transducers, which detect signal interactions with implanted metallic stents.

The primary objective of the NIMBLE-I trial is to demonstrate the technical feasibility and safety of using the NIMBLE prototype in real clinical settings. A secondary objective is to explore the potential of the device in identifying patients with significant ISR by comparing its diagnostic outputs with those of conventional invasive coronary angiography, the current standrd of care. Also, the study will alow to identify potential areas for improvement of the device.

The study plans to include up to 120 patients, of whom 30 will undergo an OCT examination to evaluate the ability of the α prototype to measure ISR. All participants must be adults with a previously implanted coronary stent and present with clinical symptoms suggestive of stent-related complications, such as chest pain or ischemic changes on an ECG. Only patients already scheduled to undergo a diagnostic coronary angiogram as part of their routine care will be eligible. Key exclusion criteria include pregnancy, the presence of implanted electronic medical devices that could interfere with microwave signals (such as pacemakers or defibrillators), or any anatomical constraints that would make transducer placement ineffective.

The clinical procedure begins with the acquisition of written informed consent. Prior to undergoing coronary angiography, each patient is evaluated with the NIMBLE device. The transducers are positioned externally on the patient's chest, over the region of the implanted stent. The measurement session is brief and completely non-invasive, with no interference in the patient's scheduled care. The system captures signal patterns and calculates a parameter which reflects potential stent obstruction. Once the NIMBLE scan is complete, the patient proceeds to undergo standard invasive angiography. Importantly, the interventional team conducting the angiography is blinded to the NIMBLE results to maintain the objectivity of comparative data.

The study's primary endpoint is the successful acquisition of data using the NIMBLE system and without the occurrence of any adverse event. The secondary endpoints include the comparison of RIS values with angiographic findings, the determination of diagnostic performance metrics such as sensitivity and specificity, and the collection of usability data from clinicians interacting with the device. The evaluation will include both descriptive and comparative statistics, and an interim analysis may be conducted following the initial patient roll-in phase.

The NIMBLE-I study follows all relevant ethical and regulatory standards, including the principles of the Declaration of Helsinki, ISO 14155 for clinical investigation of medical devices, and the EU Medical Device Regulation (MDR 2017/745). All procedures have been reviewed and approved by the local ethics committee and competent health authority. Patient confidentiality and data protection are ensured in accordance with Good Clinical Practice (GCP) guidelines.

The anticipated outcome of this study is the validation of the NIMBLE prototype as a safe and technically reliable tool that can be integrated into the clinical workflow for evaluating coronary stents. A successful pilot study will not only support the technical claims of the system but also provide essential data for the design of a larger pivotal clinical trial. Ultimately, the NIMBLE system could transform the monitoring paradigm of coronary stents by allowing non-invasive, outpatient follow-up, potentially reducing healthcare costs and procedural risks while improving patient comfort and diagnostic accuracy.