Carretera De Canyet S/n, Badalona, Spain

DIGITAL-KNEE Study: Adequately Diagnosing Total Knee Arthroplasty Loosening by Evaluating the AtMoves Knee System in a Routine Clinical Setting

InDividual, Targeted ThrombosIS Prophylaxis Versus the Standard 'one Size Fits All' Approach in Patients Undergoing Total HIp or Total KNee ReplaCemenT

Background Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are associated with an overall symptomatic venous thromboembolism (VTE) risk of about 1.3% despite the use of prophylactic anticoagulants in all patients. While not preventing all VTEs, the uniform application of anticoagulant prophylaxis is at the same time associated with a major bleeding risk of at least 0.5%. Considering that a large proportion of all patients actually have a low VTE risk, this group is unnecessarily exposed to the burden and risks of thrombosis prophylaxis. On the contrary, some patients with a high VTE risk experience a VTE despite the use of the same prophylactic anticoagulants. These VTE cases could have possibly been prevented by intensified prophylaxis. Objectives Overall objective: To study whether the application of a targeted anticoagulation strategy leads to less thrombotic and bleeding complications in this large patient group. Primary objective DISTINCT study arm 1 : To determine whether in-hospital thrombosis prophylaxis only is as effective compared with the standard thrombosis prophylaxis approach to prevent symptomatic VTE after total knee and hip arthroplasty in patients with a low VTE risk. Primary objective DISTINCT study arm 2: To determine the incidence of symptomatic VTE after total knee and hip arthroplasty in patients with an intermediate VTE risk. Primary objective DISTINCT study arm 3: To determine whether intensified thrombosis prophylaxis is more effective and equally safe compared with standard thrombosis prophylaxis to prevent symptomatic VTE in patients with a high VTE risk by comparing symptomatic VTE and bleeding complications. Methods The investigators hypothesize that: 1. In patients with a low VTE risk the thromboprophylaxis can be safely shortened to in-hospital duration only, without increasing the VTE risk (in comparison with the standard duration). In addition, this will lead to less bleeds. 2. In patients with a high VTE risk (individual predicted risk >1.5%), a therapeutic dose of thrombosis prophylaxis for 6 weeks is more effective to prevent symptomatic VTE, in comparison with the standard thromboprophylaxis. In addition, the investigators expect that the benefits of this approach (less symptomatic VTEs) outweigh the induced bleeds. In the trial participants are allocated to one of three study arms based on the postoperative venous thromboembolism (VTE) risk predicted with the TRiP(plasty) score. (Nemeth, 2024) - DISTINCT 1 (low VTE risk, <1.0%) will be a randomized study arm. - DISTINCT 2 (intermediate VTE risk, 1.0%-1.5%) will be an observational study arm. - DISTINCT 3 (high VTE risk, >1.5%) will be a randomized study arm. Participants will receive a questionnaire before surgery and 2 weeks, 6 weeks and 3 months after surgery. To assess the outcome measures. Furthermore an additional questionnaire is send 1 year after surgery if the participant experienced a VTE, major bleed or prosthesis infection. This questionnaire is focused on quality of life and joint function. Participants without such an event can be invited to complete this questionnaire as well. No extra hospital visits are needed and the surgery does not change. Sample size calculations In DISTINCT study arm 1, the expected 3-month cumulative incidence of symptomatic VTE in the control arm is 0.75%. No risk reduction or increase is anticipated, so the expected risk in the short-duration prophylaxis group is also 0.75%. With a non-inferiority limit set at 1%, a sample size of 3,130 patients is needed to achieve a power of 90%, leading to an aim to include 1,739 patients in each group, totaling 3,478 patients after accounting for a maximum dropout rate of 10%. For DISTINCT study arm 2, in the intermediate-risk group, the expected cumulative incidence of VTE within 3 months is 1.3%. With a sample size of 2,500, a 95% confidence interval width of 0.9% - 1.7% is expected, ensuring a probability of less than 15% that the upper bound of a two-sided 95% confidence interval will exceed the 2% margin. In DISTINCT study arm 3, a 3-month cumulative incidence of symptomatic VTE of 2.5% is expected in the control group. With an anticipated relative risk reduction of 50% in the intervention group, a sample size of 3,694 patients is necessary to achieve 80% power. Considering an interim analysis and a slightly stricter statistical significance level at the final analysis, a total of 3,748 patients is required, with 2,050 patients in each arm after accounting for a maximum dropout rate of approximately 9%, totalling 4,100 patients. Ethics: The study has been approved by the Medical Ethics Committee Leiden Den Haag Delft. All participants will provide informed consent.

Study in Patients With Knee Osteoarthritis Treated by Embolization Using NBGM200

Clinical Validation of BoneMRI in the Spine

Rationale: BoneMRI is a quantitative 3D MRI technique that has been developed recently by MRIGuidance BV©, which is based on a multiple gradient-echo sequence and a machine learning processing pipeline. The BoneMRI technology is capable of generating CT-like, quantitative radiodensity bone MRI images to visualize cortical and trabecular bone, allowing to assess bone structure and morphology, in addition to regular clinical MRI images. The use of BoneMRI has been investigated and clinically validated in multiple musculoskeletal studies involving the cervical spine, hip and sacro-iliac joint. In order to clinically use BoneMRI in the entire spine, the BoneMRI technology needs to be validated in that area as well, focussing on geometrical and voxelwise accuracy of the radiodensity contrast to assure accurate visualization of the osseous structures. As robustness against expected data variability between hospitals is crucial for successful machine learning algorithms, multiple MR field strengths and scanner types from different manufacturers will be included in this study. If successful, BoneMRI will facilitate a better, easier and cheaper workflow by enabling diagnosis, treatment planning and surgical navigation using a single radiological examination, without the potential hazards of ionizing radiation. Primary objective: The primary objective of this study is to investigate the performance of BoneMRI in terms of geometrical accurate visualization of the spinal osseous structures by radiodensity reconstruction when exposed to clinically relevant data variability. Study design: This study is a prospective multi-center clinical validation study, following a comparative design. Study population: Subjects referred to the radiology department for an MRI and CT scan of the spine having symptoms related to a spine disorder with suspected underlying involvement of osseous structures, will be asked to participate in this study. Duration of the study: Expectation is that it will take approximately 36-48 months to include 50 patients per center. Main study parameters/endpoints: Geometric accuracy in terms of visualization of the 3D osseous morphology of the spinal column. Nature and extent of the burden and risk associated with participation, benefit and group relatedness: The patient does not benefit from participating in this study and will receive routine care, which includes undergoing an MRI and CT scan. For research purposes an additional MRI sequence will be obtained for each patient. The CT scan is part of routine clinical care, so patients do not receive additional ionizing radiation compared to standard care. The subjects will in no way be exposed to BoneMRI as BoneMRI will not be installed at the investigation site and will not be part of the clinical workflow, nor the BoneMRI reconstructions will be part of the patient's file or decision making process of the healthcare professional. Therefore, there are no additional risks for the patients when participating in this study. This study may contribute to lower radiation doses in future patients when concluded that BoneMRI accurately visualizes the 3D morphology of the spinal osseous structures. This would render an additional conventional CT scan redundant.

A Real-World Study to Gain Clinical Insights Into Faricimab (FaReal Study)

A Study Investigating the Efficacy and Safety of Intravitreal (IVT) Injections of ANX007 in Participants With Geographic Atrophy (GA)

ARTEMIS - A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People With a Heart Attack

Rifampicin Combination Therapy Versus Monotherapy for Staphylococcal Prosthetic Joint Infection

This is a pragmatic, multicenter, randomized controlled open label trial with a non-inferiority design, comparing the efficacy of rifampicin-based combination antimicrobial therapy versus antimicrobial monotherapy with clindamycin during the oral treatment phase of prosthetic joint infection caused by Staphylococcus spp. The total duration of follow-up will be 15 months from the initial DAIR. All adult patients, aged 18 years or older, diagnosed and hospitalized with hip- or knee PJI caused by Staphylococcus spp and treated by the DAIR strategy (see Interventions), are eligible for inclusion. The diagnosis of PJI is defined according to the EBJIS 2021 criteria. Exclusion criteria are a contra-indication for rifampicin (due to a resistant strain, a proven allergic reaction, difficult drug-drug-interactions or other contra-indications as listed in the SmPC's of the antibiotics), a contra-indication for levofloxacin and clindamycin and cotrimoxazole and tetracyclines (due to a resistant strain, a proven allergic reaction, difficult drug-drug-interactions or other contra-indications as listed in the SmPC's of the antibiotics), (iii)complicated S. aureus bacteremia or concurrent endocarditis requiring long-term iv antibiotic treatment > 3 weeks , (iv) an infection for which there are no suitable antibiotic choices to permit randomization between the two arms of the trial (for instance, where organisms are only sensitive to intravenous antibiotics), (v) treatment failure before the start of oral therapy, (vi) more than two separate surgical debridements , (vii)an unsatisfactory response to initial treatment leading to continuation of intravenous therapy beyond day 21, (viii) patients with an expected life expectancy <12 months, (ix) patients with a tumor prosthesis , (x) patients receiving chemotherapy for active malignancy in the next 12 months, (xi) patients who are scheduled in advance for chronic suppressive antibiotic therapy after the initial 12 weeks of antibiotic treatment, (xii) The patient is unlikely to comply with trial requirements following randomization in the opinion of the investigator, (xiii) Pregnancy or breastfeeding, (xiv) Patients who are not able to read or communicate in Dutch or English will be excluded from participating in this study. The main trial endpoint is treatment success 15 months after DAIR (=1 year after finishing antibiotic treatment). Treatment success will be defined as absence of all of the following: (I) Infection related re-surgery of the initially affected prosthetic joint (II) New antibiotic treatment for suspected or proven infection of the index joint. (III) Ongoing use of antibiotics for the index joint at the end of follow-up. (IV) Death Secondary outcomes are (a) Quality of life, measured with the 5-level EQ-5D version (EQ-5D-5L) questionnaires. The EQ-5D-5L is a standardized and validated measure of health status developed by the EuroQol Group to provide a comprehensive generic measure of health for clinical and economic appraisal. This 'quality of life' questionnaire will be scored at the time of randomization, at week 6 after the initial surgical debridement and after 3 months. (b) Adverse events. The number of SAEs during antimicrobial treatment and follow up ii. The number of switches to a different oral regimen, iii. The number of antibiotic associated AEs (classified by the modified Hartwig and Siegel scale). (c) The number of patients developing Clostridioides difficile infection during treatment. (d) The occurrence of rifampicin resistance in bacteria in patients with a microbiologically confirmed failure of treatment.

FeAsiBility of a Treatment Free Interval in Newly Diagnosed MM Patients Treated With Daratumumab-lenalidomide-dexamethasone (HOVON174MM)

A Study to Investigate the Effect of Lepodisiran on the Reduction of Major Adverse Cardiovascular Events in Adults With Elevated Lipoprotein(a) - ACCLAIM-Lp(a)