Gunzburg

This non-interventional study aims to provide information on real-world effectiveness, safety and tolerability, management of adverse events, QoL and patient compliance of patients with HR+/HER2- early breast cancer at high risk of recurrence treated with ribociclib in combination with an aromatase inhibitor (AI) ± luteinizing hormone-releasing hormone (LHRH) with curative intent according to the current effective local summary of product characteristics. In order to put the results of patients treated with ribociclib into perspective, socio-economic data, data on QoL and patient compliance will also be collected from patients treated with abemaciclib + endocrine therapy (ET) ± LHRH as described in the current effective local summary of product characteristics. To understand reasons for treatment decision, and to analyze the clinical adoption of ribociclib + AI ± LHRH after EU approval over time, baseline data will be collected from cohorts of ribociclib + AI ± LHRH, abemaciclib + ET ± LHRH, and additionally from patients treated with ET monotherapy ± LHRH and analyzed cross-sectionally. The study is planned to be rolled out into a broad set of German and Austrian breast centers and gynecological practices to describe clinical routine in a representative subset of the local healthcare eco-system. It will gather insights into the potential benefits and risks associated with ribociclib + AI ± LHRH in the adjuvant treatment of HR+/HER2- eBC patients at high risk of recurrence. This knowledge will inform about clinical decision-making and contribute to improved patient outcomes in routine practice.

Ultrasound images will be obtained at different timepoints during the operation. First timepoint being after craniotomy (no fluids involved). Second timepoint being when some tumour is left in the bottom of the deeper part of the resection cavity (approximately 80% of tumour removed), and third timepoint being when the surgeon deems resection of the tumour to be completed. At the second and third timepoint ultrasound acquisition will be performed twice at each timepoint. Once with routinely used irrigation fluids (physiologic saline 0.9% / ringer's / lactated ringers' solution) and once with SonoClear® as part of the SonoClear® System There are two performance related primary endpoints, based on core lab assessments: 1. To assess ultrasound images obtained with SonoClear® as part of the SonoClear® System are less influenced by image artefacts compared to images obtained with standard of care irrigation fluid, by measuring the contrast-to-noise ratio (CNR). The CNR is a measure of the relative noise in the image. 2. To assess ultrasound images obtained with SonoClear® as part of the SonoClear® System compared to images obtained with standard of care irrigation fluids, by using a qualitative assessment, called the Surgeons Image Rating (SIR) scale. A Panel of Experts will assess the quality of the obtained images by answering 3 questions for each image. For SIR a 1-10 numeric rating scale, is used to measure the quality of the image according to three questions to be answered at the three different timepoints during the operation. This SIR is designed to explore whether SonoClear® as part of the SonoClear® System having shown to provide better quantitative image quality in the CNR analysis, allows surgeons to detect this improved image quality. Eventually this improved image quality should result in better decision-making during surgery about margins of excision and residual tumour resection. The primary safety event is defined as any core lab determined major Magnetic Resonance Imaging (MRI) finding when post-operative MRI is compared to pre-operative MRI that was found by the Data Monitoring Committee (DMC) to be serious and probably or definitely related to the study device OR any DMC determined serious adverse event that is probably or definitely related to the study device that occurs within 30 days of the procedure. The primary safety hypothesis declared in ACF-03 study is to prove the primary safety event rate is less than 10%. Success is demonstrated by observing 0 of these events out of 37 subjects exposed to SonoClear® ACF, i.e. the event rate is 0% with an upper two-sided 95% confidence limit less than 10%. With an event rate of less than 10% for major neurotoxicity events that are serious and probably or definitely related to the device, the benefit of a clearer image for the neurosurgeon balances the potentially increased risk. This study expands the number of patients to evaluate the safety outcome. The primary safety event rate will be evaluated also in a total group of 60 patients, 45 using SonoClear® ACF and 15 using the SonoClear® System.

Patients with established continuous ICM monitoring from the prospective, randomized, multicenter study Find-AF 2 (NCT04371055) are recruited for this trial. Find-AF 2 is being carried out at Leipzig University Hospital since 2020 with the help of about 50 study centers throughout Germany. The AppleWatch Series 10, a device from the current market leader, was chosen because extensive data from clinical trials is already available and data regarding the market leader has particular societal relevance. The AF detection algorithm is based on photoplethysmography (analysis of the pulse current curve) and semicontinuous monitoring. If a rhythm irregularity is detected during hourly measurements, the measurement interval is shortened. If this finding is confirmed in several consecutive measurements, the user is notified. In this pilot study, patients are trained to record a 30-second ECG with the AppleWatch in the event of notification. This is done by placing the other hand on the crown of the watch. The report will then be transmitted. The AppleWatch must be paired with another Apple device (e.g. iPhone) to use the ECG app and must be charged daily (battery life 18 hours). Our patients are provided with an iPhone for study use and are trained in using the AppleWatch. The AppleWatch is not certified as medical device, but the ECG data collected by the AppleWatch will be used for research purposes only and not for therapeutical or diagnostical purposes. The second wearable will be the PulseOn device. The battery lasts over two weeks. No additional device is needed for writing an ECG. AF screening is also performed photoplethysmographically. In the case of detection of an arrhythmic pulse curve, this is communicated by vibration. By laying the other hand on the device, a 1-channel ECG is performed for registration. Regular data transfer is done at the patient's home via a gateway device to the PulseOn server. The Core lab will monitor the data transmission. Although PulseOn is a certified medical device, the ECG data collected by the PulseOn device will be used for research purposes only and not for therapeutical or diagnostical purposes. The ICM is the gold standard for recording relevant arrhythmias.