Title Promoter Affiliations Abstract "The effect of extended heart failure Audit and Feedback on cardiovascular hospitalizations in general practice: a randomized controlled trial" "Bert Vaes" "Academic Center for General Practice" "Heart failure (HF) is a prevalent disease affecting 1-3% of the general population and up to 20% of patients aged 80 and older. HF has a large impact on morbidity, mortality and quality of life. On top of the clinical and epidemiological impact, it also has an important economic impact, largely because of frequent (re)hospitalizations. Optimizing the early and adequate identification of HF in general practice, leads to an earlier start of treatment and reduces the risk of hospitalization. However, identifying patients with HF in general practice is challenging since symptoms and signs are non-specific, particularly in elderly patients. Additionally, under-diagnosis and under-registration, as well as over-diagnosis was observed. Based on a systematic review on methods to identify HF patients in general practice an extended clinical Audit was developed and implemented in the GPs’ electronic health record (EHR) to optimize the early and adequate identification of HF. We studied the feasibility of the extended Audit and found a 62% increase in identified HF patients. Therefore, we want to study the effect of heart failure Audit and feedback on cardiovascular hospitalizations in general practice through a randomized controlled trial (RCT)." "Using a humanoid robot to provide pain neuroscience education to children with chronic pain: a randomized controlled trial." "Kelly Ickmans" "Physiotherapy, Human Physiology and Anatomy" "Chronic pain is common in children and significantly interferes with their daily functioning. Pain neuroscience education (PNE) has proven to be an effective way of improving chronic pain in adults and preliminary proof-of-concept-findings in pediatric chronic pain are highly promising. Furthermore, previous research has shown that children are eager, receptive and even‘pre- programmed’ to engage with robots. Accordingly, using a robot for providing PNE may facilitate effective transmission of information and hence, increase child’s usage of coping strategies they are taught. The main objective is to examine whether robot-assisted parent engaged PNE (RA-PNE4Kids) is effective in improving pain-related functional disability and pain intensity in children with chronic pain compared to PNE provided by a therapist only and engaged by a parent (PNE4Kids). A multicenter randomized controlled trial (RCT) with 6-month follow-up among children with chronic pain will be performed. Eighty children between 6 and 12 years old who are suffering from chronic pain will be randomized to the experimental (RA-PNE4Kids) or control intervention (PNE4Kids). The primary outcome measure includes child’s functional disability; secondary outcomes include child’s pain intensity, parent’s catastrophic thinking about their child’s pain and child’s and parent’s pain- related fear." "Home-based PHysical rehabilitatiOn after livEr traNsplantation and Impact of eXercise intensity: a Randomized Controlled Trial [PHOENIX-RCT]" "Diethard Monbaliu" "Abdominal Transplantation, Department of Rehabilitation Sciences" "Cardiovascular and metabolic morbidity and mortality following liver transplantation are a major problem. The etiology is primarily rooted in lifelong immunosuppressive therapy, a sedentary lifestyle, and poor physical fitness. We hypothesize that personalized home-based exercise training for 6 months, succeeded by a preference-tailored physical activity intervention in de novo liver transplant recipients is safe, cost-efficient, and effective in sustainably improving physical fitness (VO2peak as primary outcome) and cardiovascular health. 148 liver transplant recipients will be randomly allocated to usual care (n=74) versus an exercise and physical activity intervention (n=74). The first training phase is performed at moderate intensity and supervised by the local physiotherapist. The second training phase is remotely mediated and performed at either moderate (n=37) or a combination of moderate and high intensity (n=37). Follow-up period is 2 years in duration. Study findings will be easily implementable in daily practice." "Preventing Relapse After Successful ECT for Depression– A randomized controlled trial on lithium as add-on to personalized maintenance ECT." "Didier Schrijvers" "Collaborative Antwerp Psychiatric Research Institute (CAPRI)" "Although electroconvulsive therapy (ECT) is an effective treatment for depression, preventing relapse after successful ECT remains a major challenge. In the PRASED-study, a large multicentre RCT, we evaluate the effectiveness of three strategies to reduce relapse: an algorithm-based symptom-driven form of maintenance-ECT (M-ECT), with antidepressants, with or without lithium. In the four treatment centers, patients that are referred for ECT for depression will be screened for eligibility. In phase 1 300 patients are treated with an acute course of brief pulse ECT, combined with open label nortriptyline or venlafaxine. Patients that achieve remission, are considered eligible for phase 2 of the study. In this continuation phase, open label antidepressants are continued and algorithm-based, symptom-driven M-ECT is started for the next six months. Patients will be randomized to receive either lithium or not. After six months, patients enter phase 3, a naturalistic follow-up of mood at 3 and 6 months after completion of phase 2. The combination of antidepressants, personalized M-ECT and lithium has been studied in an elderly population and proved to be very effective, but the efficacy in a severely depressed population of all ages has never been assessed. This project holds great promise for reducing relapse rates after successful ECT, thereby being of potential impact for a vulnerable group of patients with an often recurring and debilitating major depressive disorder. Apart from a significant positive medical impact, reducing relapse rates eventually also has a socio-economic impact by reducing health care costs." "Preventing Relapse After Successful ECT for Depression - A randomized controlled trial on lithium as add-on to personalized maintenance ECT." "Pascal Sienaert" Neuropsychiatry "The current project is designed to study some promising relapse prevention strategies in a well-designed but challenging RCT." "Which exercises to prescribe in patients with subacromial pain? A multi-center randomized controlled trial." "Filip Struyf" "Movement Antwerp (MOVANT)" "Shoulder pain is the third most common musculoskeletal disorder, with estimated lifetime prevalence around 10%. The prevalence for daily non-specific shoulder pain in the working population is around 12%, and up to 23% of the workforce seeking professional help with a shoulder related disorder have been sick-listed for at least one week. People with shoulder pain are often disabled to the point where they cannot live a normal life, suffering from sickness absence and poor quality of life. Clinically, subacromial pain is the most common form of complaint and causes a great loss of shoulder function, which accounts for 33% of all shoulder-related healthcare contacts. Previous studies have clearly shown that exercises are the preferred first choice of treatment for patients with subacromial pain. However, there are some studies supporting the benefits of using targeted strength training in patients with subacromial pain, but it is not clear what the best type of exercise combined with the patient response a health care provider should prescribe: should the patient feel pain during the performance of an exercise, or should pain be avoided? The present project aims to answer the following research questions: Which type of intervention (pain acceptance/pain avoidance) is superior to self-reported improved patient reported shoulder pain, function and quality of life? And which type of intervention (pain acceptance/pain avoidance) is superior to improved changes in the tendon structure, measured by Ultrasound? An RCT study will be conducted as a randomized, controlled, blinded multi-center trial in both public and private practice settings in Denmark, Belgium, Spain and The Netherlands with inclusion of patients from National Health Service musculoskeletal orthopedic outpatient departments and/or general practitioners. Both intervention groups will receive eccentric, concentric and isometric exercises of the same load, frequency, progression etc. However, the difference between both intervention groups will be based on the specific movement, which is either pain aggravation or not. The project is organized in cooperation between University of Antwerp (Belgium), University of Malaga (Spain), University College Rotterdam (The Netherlands) and University of Southern Denmark (Denmark). With this, the current project will have the assistance of the national and European shoulder networks in order to be sure of sufficient shoulder pain patients with different cultural backgrounds. This project will contribute to clarify the best treatment option in the management of subacromial pain. Clinicians and care providers will be benefited of this increase in the body of knowledge, in order to steer subacromial pain treatment and to improve clinical decision-making, and reducing the chronification of SPS. With this, the present project also attempt to reduce the massive economic burden of subacromial shoulder pain on society." "ITI Research Grant Application 2021-1612: Alveolar ridge preservation with immediate or delayed implant placement: a multicenter randomized controlled trial" "Jan Cosyn" "Department of Oral Health Sciences" "Alveolar ridge preservation (ARP) can be combined with immediate implant placement (IIP) or delayed implant placement (DIP). Both approach have specific advantages and disadvantages, yet RCTs have not been published on the need for soft tissue augmentation.The hypothesis is that ARP + IIP reduces the need for soft tissue augmentation since the peri-implant mucosa can be immediately supported with a provisional crown. In contrast, ARP + DIP allows the tissues to collapse. The primary objective of this multicenter RCT is to compare ARP+IIP with ARP+DIP with respect to the need for soft tissue augmentation 6 months after ARP." "CHaT - Changing Tactics? Changing treatment technique in case of early nonresponse during ECT for major depression: a randomized trial." "Pascal Sienaert" Neuropsychiatry "Major depressive disorder (MDD) affects one in six adults in their lifetime and imposes a considerable burden of disease on the patient. Despite the widespread use of antidepressant medication, after several treatment steps, at least a third of patients will fail to achieve remission. For patients with so-called difficult-to-treat depression, not responding to several augmentation or combination attempts, electroconvulsive therapy (ECT) has the best empirical evidence, yielding high response and remission rates. ECT is also used when a rapid antidepressant response is required, such as in patients who are either severely depressed, highly suicidal, or both. If a patient responds to ECT, the majority of the improvement is witnessed early in the treatment course. If early improvement is deemed insufficient, historically it is common practice to switch from a right unilateral (RUL) to a bitemporal (BT) electrode placement. However, no randomized controlled trial (RCT) data are available to support this ubiquitous clinical practice. Therefore, an RCT was designed to address which treatment strategy (continue RUL ECT or switch to BT) speeds up recovery and has the least impact on memory function. In this double-blind randomized trial we will include data of 196 patients, who fail to show early response (i.e. after four treatment sessions). They will be recruited at the four participating centres and will be randomly assigned to one of the two study arms. As primary objectives, we aim to address the antidepressant efficacy and the cognitive impact of switching electrode placement from RUL to BT (arm a) compared to continuing with RUL (arm b), in case of non-response after four RUL ECT sessions." "ProBio: an outcome-adaptive, multi-arm, open-label, multiple assignment randomized biomarker-driven trial in patients with metastatic castration-resistant prostate cancer" "Piet Ost" "Department of Human Structure and Repair" "Androgen deprivation therapy (ADT) is the Standard systemic therapy for men with advanced prostate cancer. Although initially beneficial, inevitably all patients will progress to the lethal castration-resistant state of the disease. Metastatic castration-resistant prostate cancer (mCRPC) affects approximately 1.500-2.000 men in Belgium every year. Cytotoxic chemotherapy and newer endocrine agents are available, but they are expensive and lack predictive treatment biomarkers. Additionally, there are currently no clear guidelines on treatment choice or treatment sequencing, which leads to a trial-and-error approach in the treatment of men with mCRPC. This will result in an unsustainable situation for prostate cancer care, accompanied with a major cost burden on health care. mCRPC is a heterogeneous disease, where different metastases may have a different molecular build-up, resulting in two types of resistance when treating this disease: intrinsic or acquired. Whereas intrinsic (or primary) resistance is already present before the start of therapy, acquired resistance develops eventually in all patients due to the selection pressure from the administered therapy. Both resistance mechanisms emphasise the need for treatment personalisation, which is the goal of the current project. Our previous Swedish-Belgian collaborative studies, supported by Kom Op Tegen Kanker, have demonstrated how liquid biopsies, such as circulating tumour cells and plasma-derived cell-free DNA (cfDNA) can be an excellent surrogate to interrogate these resistance mechanisms in a non-invasive way. We and others have explored the clinical validity of molecularly-guided therapy selection in mCRPC and have identified biomarker signatures that might help us guide treatment choice. However, the clinical utility of these signatures has not been demonstrated, and requires validation in the context of a randomised controlled trial (RCT). The proposed project application aims towards the initiation of the Prostate Biomarker (ProBio) trial, which is a Swedish- Belgian collaborative effort with several novel approaches. It is adaptive, multi-arm, open-label, multiple assignment, and a biomarker driven phase 3 RCT in patients with mCRPC. Here, we will analyse cfDNA as a real-time liquid biopsy using a prostate-specific biomarker panel, designed and validated to detect 1) mutations in 78 genes, 2) genomic structural rearrangements (GSRs) in 11 prostate cancer-associated genes, 3) genome-wide copy number alterations, 4) 63 microsatellites to infer microsatellite instability (MSI), 4) tumour mutational burden and 5) estimate the circulating tumour DNA (ctDNA) fraction. Using pre-defined biomarker signatures, focused on genomic alterations in AR and TP53, DNArepair deficiency and TMPRSS2-ERG fusions, we will select which new line of systemic therapy will be initiated, and comparing these patients to the standard-of-care. The statistical design of ProBio is novel, since the randomisation probabilities for a given experimental systemic therapy are subjective to change as the trial evolves and learns from prior experience. Secondly, ProBio implements a re-randomization of non-responding patients, providing essential insights in optimal treatment sequencing. The hypothesis is that treatment decisions based on molecular profiling of cfDNA will significantly prolong the progression-free survival (PFS), resulting in increased response rates, which in turn would translate into improved overall survival (OS). Additionally, secondary endpoints encompass Quality of life (QoL), heath economy and adverse event profile comparison between different trials arms. This project could result in the first validation of the clinical utility of the liquid biopsy in the standard-of-care in mCRPC." "The effectiveness of a blended care program for the discontinuation of benzodiazepines use for sleeping problems in primary care: a clustered randomized trial." "Sibyl Anthierens" "Katholieke Universiteit Leuven, Primary and interdisciplinary care Antwerp (ELIZA)" "Introduction Problematic benzodiazepine use is a global health issue. Although the adverse side effects of longterm use of benzodiazepines are well known, it remains difficult to implement interventions for discontinuation in primary care. Considering the success of blended care for the treatment of sleeping disorders and the support of substance use disorders, evidence suggests that a blended care approach, combining face-to-face consultations with the general practitioner with web-based self-learning by the patient, is beneficial for the discontinuation of chronic benzodiazepine use for primary insomnia in general practice. Therefore, the aim of this study is to evaluate the effectiveness of such an approach for the discontinuation of benzodiazepine and zdrugs ((z-)BZD) use in the long term and evaluate the implementation process. Methods and analysis This study is a multicenter, pragmatic, cluster randomized controlled trial with 1200 patients, included by 120 general practitioners. Allocation to usual or blended care happens at the level of the general practice in a 1:1 ratio using a block randomization system stratified per language. The study population consists of adult primary care patients who have been using (z-)BZD for primary insomnia on a daily basis for at least six months. Primary outcome measure is the proportion of patients that discontinued (z-)BZD at 12 months assessed by toxicological screening for (z-)BZD in urine. Secondary outcomes include discontinuation of (z-)BZD at 6 months, quality of life, and the number of defined daily doses of (z-)BZD prescribed. Data will be collected using a study-specific online platform and analyzed using the intention-to-treat approach. The process of implementing blended care will be evaluated in a nested study."