Zolder, Belgium

Planning Operative Strategy Using a Digital Renal Artery Clamping Tool

BACKGROUND: For patients diagnosed with localized kidney cancer, two main options exist to surgically remove the kidney tumor. During radical nephrectomy (RN), the entire kidney is removed. During partial nephrectomy (PN), only the tumor is resected, safeguarding the function of the remaining healthy kidney tissue. This last procedure is preferred, but not always technically feasible. To resect only the tumor, a balance has to be found in the clamping approach: clamping the blood supply to the kidney assures bloodless tumor resection, yet compromises the postoperative renal function due to the temporary ischemia. Tumor resection without clamping on the other hand, might lead to substantial blood loss. That is why "selective clamping" (SC) is proposed. In this approach, only those selective arteries are clamped that perfuse the zone including the tumor. The main drawback of this strategy is that it is often not clear which arteries should be clamped based on standard preoperative imaging, while misjudgment can lead to a high-risk surgery with excessive bleeding or prolonged ischemia time. Therefore, RN is currently recommended when PN is considered not feasible. Better prediction of individual kidney perfusion will allow to perform more frequently a PN and thus save healthier kidney tissue. Additionally, it is difficult for patients to assess their own individual oncological situation based on 2D CT images. With this project, the investigators want to offer the surgeon an easy-to-use virtual planning tool that facilitates the decision-making process regarding the feasibility of PN and the corresponding optimal clamping strategy. This tool uses virtual 3D models based on CT scans, to visualize precise information on the different anatomical structures and perfusion zones. This may also improve patients' understanding of their own individual situation. The proposed new tool (DIPLANN-tool) for predicting kidney perfusion zones on a segmented 3D model during robot-assisted partial nephrectomy (RAPN) for localized renal cancer demonstrated high accuracy when planning selective clamping (SC) for RAPN. However, the tool's clinical added value still needs to be confirmed. Therefore, a randomized controlled trial using a study and control group is the preferred study design. DESIGN: A confirmatory, multicentric, unblinded, randomized, controlled, pivotal trial using parallel group assignment and stratified randomization. Experimental group: the use of the DIPLANN model + conventional CT imaging for preoperative planning and perioperative guidance. Control group: the use of only conventional CT imaging for preoperative planning and perioperative guidance (= current standard of care). METHODOLOGY: Sample size calculation: 235 patients. Patients will be randomized according to a 1:1 allocation ratio to either the experimental group (the DIPLANN-tool in combination with conventional CT imaging) or the control group (conventional CT imaging alone), using permuted block randomization with blocks of varying size. Randomization will be stratified on the following variables: - Whether SC is deemed possible according to the DIPLANN-tool in combination with conventional CT imaging or on conventional CT imaging alone, as assessed by an independent surgeon (between inclusion and randomization) who will not be not involved in the RAPN surgical procedure (yes vs no). - Hospital where surgery is performed. - PADUA classification (low (<8) and intermediate (8-9) vs high-risk (>9)). In case of multiple masses, the mass with the highest individual PADUA classification will be used. PRIMARY OBJECTIVE: To assess if the DIPLANN-tool in combination with conventional CT imaging is superior to conventional CT imaging alone, with respect to planning and performing as planned a SC strategy during RAPN, in patients diagnosed with localized kidney cancer who are planned to undergo renal cancer surgery and in whom SC is deemed possible either according to the DIPLANN-tool in combination with conventional CT imaging or according to conventional CT imaging only, as assessed between inclusion and randomization by an independent surgeon. SECONDARY OBJECTIVES: - To assess if the DIPLANN-tool in combination with conventional CT imaging is superior to conventional CT imaging alone, with respect to planning and performing as planned a SC strategy during RAPN, in patients diagnosed with localized kidney cancer who are planned to undergo renal cancer surgery. - To compare the DIPLANN-tool in combination with conventional CT imaging to conventional CT imaging alone with respect to: patients' health, patients' insight, and surgeons' benefits. ENDPOINTS: The primary endpoint is planning and performing as planned a SC strategy. Secondary endpoints include patients' health, patients' insight and surgeons' benefits. Extended listing of all outcome measures: see below.

The TRICURE EU Pivotal Study

The study is a multi-center, prospective single arm study designed to evaluate the safety and performance of the TRiCares Topaz Tricuspid Valve Replacement System.

AI-Powered ECG Detecting Culprit Vessel Blood Flow Abnormality in ACS

The Application of Positive End-Expiratory Pressure in Out-of-Hospital Cardiac Arrest: The Lazarus-PEEP Trial.

Introduction: Sudden cardiac arrest is a significant cause of mortality, with an estimated annual incidence of 84 cases per 100,000 individuals in Europe. Effective cardiopulmonary resuscitation (CPR), including proper ventilation, is crucial for survival. However, the interplay between ventilation and circulation during CPR is complex and not fully understood. While ventilation is necessary for oxygenation, excessive hyperventilation and high intrathoracic pressures can be detrimental. Positive End-Expiratory Pressure (PEEP) may improve oxygenation and ventilation by maintaining alveolar patency and improving oxygenation. Previous observational studies have suggested that PEEP might enhance the rate of Return of Spontaneous Circulation (ROSC) and improve short-term outcomes. However, no prospective randomised clinical trials have been conducted to confirm these findings. The Lazarus-PEEP trial aims to address this gap by evaluating the efficacy and safety of PEEP during CPR for out-of-hospital cardiac arrest (OHCA) patients. Methodology: The study will be conducted at Ghent University Hospital and three non-university hospitals in Belgium, enrolling adult patients who experience non-traumatic OHCA and are intubated and ventilated during resuscitation efforts by an advanced life support (MUG) team. Participants will be randomised to receive either PEEP at 5 cm H2O or no PEEP (0 cm H2O) during CPR. Custom-built sensors will measure tracheal airflow and pressure, while additional data on CPR quality and patient outcomes will be collected. The trial's primary outcome measure is the rate of ROSC, with secondary outcomes including survival to hospital admission and discharge, as well as neurological outcomes at discharge. Outcome: The study will evaluate the effectiveness of PEEP in improving ROSC rates, short-term survival, and neurological outcomes. Safety profiles will also be examined, focusing on adverse effects such as barotrauma and increased intrathoracic pressures. Comprehensive data collection will provide insights into the physiological impact of PEEP during CPR and its feasibility in a pre-hospital setting. Conclusion: The Lazarus-PEEP trial aims to gather strong evidence on the potential advantages and risks of utilizing PEEP during CPR for OHCA patients. The results will inform evidence-based guidelines and enhance resuscitation practices, potentially leading to improved patient outcomes. The findings will be disseminated through influential journals, major scientific conferences, and public data-sharing platforms to ensure widespread accessibility and impact.

A Phase III Renal Outcomes and Cardiovascular Mortality Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin in Participants With Chronic Kidney Disease and High Blood Pressure

The purpose of this study is to investigate the efficacy, safety, and tolerability of baxdrostat in combination with dapagliflozin, compared with placebo and dapagliflozin, in reducing the risk of the composite of > 50% decline in eGFR, kidney failure, or CV death, in individuals with CKD and HTN. This study consists of a 4-week dapagliflozin Run-in Period for participants untreated with SGLT2i at screening, and a double-blinded period where participants will receive either baxdrostat/dapagliflozin or placebo/dapagliflozin. Site visits will take place at 2-, 4-, 8-, 16-, 34, and 52-weeks following randomisation. Thereafter visits will occur approximately every 4 months. The study closure procedures will be initiated when the predetermined number of primary endpoint events is predicted to have occurred ie, the PACD. All randomised participants including any participants who have prematurely discontinued study intervention will be scheduled for a SCV within a few weeks of the PACD. This period can be extended by the Sponsor. In case of premature discontinuation of blinded study intervention, participants will continue in the study and receive dapagliflozin 10 mg, unless the participant meets dapagliflozin specific discontinuation criteria. If study intervention is temporarily or permanently discontinued, the participant should remain in the study, and it is important that the scheduled study visits (including the PTDV for participants with permanent discontinuation of study intervention) and data collection continue according to the study protocol until the SCV.

Prospective, Multicenter, Single-Arm Observational Study to Confirm the Safety and Clinical Performance of the Oscar Peripheral Multifunctional Catheter for the Dilatation of Lesions in the Femoral, Popliteal and Infrapopliteal Arteries (BIO-OSCAR First)

This is a prospective, multicenter, all-comers observational study. Primary endpoint was procedural success (defined as a combination of successful primary target lesion crossing, residual stenosis of ≤30% following vessel preparation and before definite treatment) and absence of procedural complications (defined as target vessel perforation or rupture, acute occlusion, and distal embolization).

Real-life Evaluation of the Efficacy of Biologicals in Chronic Rhinosinusitis With Nasal Polyposis (CRSwNP)

Chronic rhinosinusitis with nasal polyps (CRSwNP) has a prevalence of 5-10% in adults. It is often associated with other comorbidities, such as asthma (30-70% of CRSwNP patients) and aspirin exacerbated respiratory disease (AERD) (16% of CRSwNP patients) leading to a significant reduced quality of life (QoL). CRSwNP is diagnosed in patients with nasal polyps who have 2 or more of the following symptoms for more than 12 weeks: - Nasal blockage or nasal congestion - Runny nose or postnasal drip - Impaired sense of smell - Facial pain/pressure. Nasal rinses, intranasal or systemic corticosteroids, long-term antibiotics, and sinus surgery are the current standard of care. However, many patients fail to achieve complete therapeutic benefit and relapse after time, even after surgery. Moreover, oral corticosteroids are associated with significant side effects, and repeated sino-nasal surgery becomes progressively more complex with higher risk of complications. Patients with CRSwNP and most patients with asthma share a common type 2 inflammatory response, characterised by elevated levels of interleukin (IL)-4, IL-5, IL-13, eosinophils, T helper 2 (Th2)cells, and type 2 innate lymphoid cells. In addition, locally produced immunoglobulin E (IgE) is able to activate mast cells and induce local inflammation in CRSwNP. Biologicals are a specific kind of treatment with recombinant DNA-derived humanized monoclonal antibody that selectively binds specific targets in the inflammatory cascade which contributes to the pathophysiology of CRSwNP. Different biologicals have already been reimbursement for the treatment of Asthma for years, slowly these biologicals start to get their approval and reimbursement for CRSwNP. In Belgium (omalizumab (Xolair®), mepolizumab (Nucala®) and dupilumab (Dupixent ®) are reimbursed for patients with CRSwNP. Their efficacy has been demonstrated through large double-blind placebo-controlled clinical studies. However, until now only very limited reports on real-world data regarding this therapy have been published. This real-world data is important because it enables us to go beyond data gathered throughout a traditional randomised controlled trial (RCT). Traditional RCTs gather data from a controlled sample population with limited comorbidities and concomitant medications, who are likely to be compliant with the study requirements, whereas in real life patients might have poorer performance status and compliance and consist of a higher proportion of elderly patients. Therefore, this real-world data study aims to investigate how clinical outcomes of biologic therapy in real-world application (real-world efficacy) corresponds to outcomes in clinical trials (efficacy) and to look into factors that might explain an efficacy gap.

Separation Surgery Followed by Stereotactic Ablative Body Radiotherapy (SABR) Versus SABR Alone for Spinal Metastases

In this study, patients with malignant epidural spinal cord compression (MESCC), Bilsky grade 1c, 2 and 3 who are ambulatory with or without aid (rollator, cane, one persons help) will be treated by separation surgery followed by SABR (5x 8.0 Gy postoperative) (control arm) or SABR alone (5x 8.0 Gy) (study arm). The primary objective of the study is investigating the effect of SABR compared to separation surgery followed by SABR in ambulatory patients with MESCC on retaining ambulatory function. The primary endpoint of the study is ambulatory function 3 months post treatment defined as: being able to walk 10m without aid; being able to walk 10m with aid (cane, rollator, one persons help, ...); not being able to walk. Secondary outcomes are local control, progression free survival, early and late adverse effects, quality of life, effect on pain and need for reintervention. For each participant, the study starts once written informed consent is provided and is composed by 4 study phases: a screening phase, randomisation, a treatment phase and a follow-up phase. The screening phase will allow for assessment of subject eligibility before randomisation and treatment. Demographic data, disease and spinal metastases characteristics and previous anticancer therapies will be recorded. Once all screening procedures are completed, eligibility will be determined according to the inclusion/exclusion criteria. Randomisation will be performed in a 1:1 ratio to the control arm (separation surgery followed by SABR) and the study arm (SABR) using an electronic randomisation tool in the eCRF. Treatment will be aimed to start as soon as possible, but certainly within 21 days after randomisation (surgery or upfront SABR). Surgical planning is done by the treating neurosurgeon in the participating center where the patient was included. Image-guided fractionated SABR using a SIB technique to the high-dose PTV will be delivered in 5 fractions of 8 Gy to a total of 40 Gy and to the conventional-dose PTV delivered simultaneously in 5 fractions of 4 Gy to a total of 20 Gy. At 6 weeks (+/-1 week) after the last RT session following information will be obtained (preferentially by digital consult): 1. Ambulatory status defined as: being able to walk 10m without aid, being able to walk 10m with aid (cane, rollator, one persons help, ...), not being able to walk 2. WHO performance status 3. Acute and late toxicity assessment: as measured with CTCAE version 5.0 4. Need for re-intervention, date and type of reintervention (surgery or radiotherapy), reason (wound infection, neurologic decline, loss of ability to walk or other) 5. Pain response: VAS pain score 6. Survival data (survival status, date of death, primary cause of death) At 3 and 6 months (+/-3 weeks) after the last RT session following information will be obtained by physical or digital consult: 1. Ambulatory status defined as: being able to walk 10m without aid, being able to walk 10m with aid (cane, rollator, one persons help, ...), not being able to walk 2. WHO performance status 3. Concomitant medications and systemic anticancer therapies 4. QoL according to the EORTC QLQ-C15 & BM22 questionnaires 5. Acute and late toxicity assessment: as measured with CTCAE version 5.0 7. Need for re-intervention, date and type of reintervention (surgery or radiotherapy), reason (wound infection, neurologic decline, loss of ability to walk or other) 6. Pain response: VAS pain score 7. Physical examination: body weight 8. Local control 9. Survival data (survival status, date of death, primary cause of death) At 12 and 24 months (+/-3 weeks) after the last RT session following information will be obtained (preferentially by digital consult): 1. Ambulatory status defined as: being able to walk 10m without aid, being able to walk 10m with aid (cane, rollator, one persons help, ...), not being able to walk 2. Need for re-intervention, type of reintervention 3. Survival data (survival status, date of death, primary cause of death) 4. Local control (only if information is available in medical record as per standard of care)

Salvage Stereotactic Body Radiotherapy of the Prostate Bed for Biochemical Recurrence After Radical Prostatectomy.

This is a multicentric randomized seamless phase II/III study comparing SBRT to conventional RT or moderately hypofractionated RT on the prostate bed. All subjects will be randomly assigned in a 1:1 ratio: 1. Experimental arm: Radiotherapy treatment in 5 fractions. 2. Control arm: Radiotherapy treatment within a normofractionated or mildly hypofractionated schedule. For the control arm, each participating center can choose between a normofractionated schedule (32 to 35 treatment sessions) and a moderately hypofractionated schedule (20 sessions).

TRIcvalve BiCAVal Valve System for Severe Tricuspid Regurgitation (TRICAV-I)

This is a prospective multicenter clinical investigation designed to evaluate the safety and effectiveness of the TricValve® Transcatheter Bicaval Valve System for improving outcomes in symptomatic subjects with severe TR deemed by the local Heart Team to be at high risk for tricuspid valve surgery. Patients who meet all of the study inclusion criteria, will be treated with the TricValve System. After the intervention, patients will be followed up closely for 12 months. Long term safety and efficacy data will be collected annually up to 5 years.