Clinical trials

Radiotherapy cures many cancers but can cause late radiation-induced tissue injury (LRTI), leading to long-term symptoms from the bladder and bowel and reduced health-related quality of life (HRQoL). Hyperbaric oxygen therapy (HBOT) is an established treatment that reduces chronic inflammation and promotes tissue repair. Randomized studies have demonstrated improvements in symptoms and quality of life, but only a small proportion of affected patients receive HBOT. This study aims to longitudinally describe a cohort of patients with LRTI treated with HBOT at Karolinska University Hospital and to analyze associations between treatment, timing, and patient characteristics. The goal is to improve understanding of which patients benefit most from HBOT and when treatment should be initiated.

ACE-AF is a multicenter randomized study in people aged 78 years and older with symptomatic atrial fibrillation (AF). AF is a common heart rhythm disorder in older adults and can cause reduced quality of life and lead to serious complications such as stroke and heart failure. The study compares two established treatment strategies: 1. Catheter ablation (an invasive procedure aimed at reducing AF by electrically isolating triggers in the heart, primarily through pulmonary vein isolation), and 2. Optimized medical therapy without AF ablation (medications for rate and/or rhythm control; AV node ablation with pacemaker may be used if clinically indicated according to routine care). Participants are randomized 1:1 to one of these strategies. All participants will receive an implantable loop recorder (a small heart rhythm monitor placed under the skin) to continuously track heart rhythm and measure AF burden over time. The study has two co-primary outcomes assessed over 24 months: 1. a composite of major clinical events (all-cause mortality, stroke, major bleeding, cardiac arrest, or hospitalization due to heart failure), and 2. patient-reported health-related quality of life (HRQoL), measured by the SF-36 "General Health" domain. ACE-AF will provide evidence to guide treatment decisions for very elderly patients with symptomatic AF and help identify which patients benefit most from an ablation-based strategy compared with optimized medical therapy.

The goal of this clinical trial is to evaluate the safety and tolerability of increasing doses of \[177Lu\]Lu-AKIR001, both in relation to tolerable activity of lutetium-177 and the absorbed protein mass dose of AKIR-001 in patients with irresectable or metastatic CD44v6-expressing solid malignancies for whom no reasonable systemic treatment options are be available. The main question it aims to answer is: • What is the toxicity profile of the study drug \[177Lu\]Lu-AKIR001 according to the rate of Dose Limiting Toxicities and (Severe) Adverse Events? Participants will receive one \[177Lu\]Lu-AKIR001 infusion followed by a 6-week safety follow-up period, which can be extended up to 12 weeks. Possible additional infusions of the trial drug, up to a maximum number of four, can be given when clinical benefit is noted and toxicity is deemed acceptable.

This is a phase 4 non-interventional single center trial. We aim to prospectively include patients scheduled to undergo CAR-T therapy at ME CAST, Karolinska University Hospital Huddinge, to study ICANS. Because ICANS develops rapidly, inclusion during this potentially life-threatening phase would not be feasible; patients must therefore be enrolled before they start treatment. We aim to include patients who are clinically at high risk of developing ICANS. The risk of ICANS is assessed based on diagnosis, tumor burden, CAR-T product, and inflammatory status prior to treatment initiation. We plan to compare patients who develop ICANS grade 2-4 with patients who develop no ICANS or at most grade 1. Patients will undergo Positron Emission Tomography (PET) with two different tracers: (1) PBR28 for TSPO, which provides a measure of brain inflammation-this ligand binds to microglial cells-and (2) 11C-UCB-J for SV2A, which provides a measure of synaptic density in the brain. The results will be compared with magnetic resonance imaging. We will collect blood, bone marrow and cerebrospinal fluid (CSF) samples from this patient cohort. Samples will be taken from all patients before, during, and after CAR-T treatment. Participation in the study also includes computer-based cognitive testing, neuropsychological evaluation and genetic testing to determine whether the patient has receptors allowing binding of the TSPO radioligand used during PET imaging.

Patients undergoing allogenic stem cell transplantation are regularly followed up in the outpatient clinic at Karolinska University Hospital. Here, patients are offered participation the fatigue study measuring both fatigue and cognitive impairment systematically by international standard. Meanwhile liquor samples and advanced PET imaging techniques are available for these patients as part of a research project allowing extensive immunological and radio-morphological studies.

The Robocop trial is an international multi-centre, single blinded, randomized controlled superiority trial conducted in centres experienced in robotic-assisted liver surgery. Eligible patients for radical cholecystectomy will be randomized in a 1:1 ratio to undergo robotic-assisted or open resection within an enhanced recovery setting. The primary endpoint is time to functional recovery. Secondary endpoints include length of hospital stay, resection margin, number of retrieved lymph nodes, postoperative complications, quality of life, abdominal wall complaints and direct and indirect costs.

Background: Severe acute kidney injury (AKI) among critically ill patients is sometimes treated with renal replacement therapy (RRT), and in Sweden continuous RRT (CRRT) is the dominant modality used in this population. * The optimal timing of renal replacement therapy (RRT) initiation in critically ill patients with acute kidney injury (AKI) is unknown * No consensus to guide clinical practice on this issue * Lack of consistency regarding outcome measurements; should we look at morbidity or mortality? * Wide variability in the timing of RRT initiation in the intensive care unit (ICU) population Hypothesis: This is an important knowledge gap in the support of critically ill patients with AKI and we hypothesize that early initiation of RRT is beneficial. Methods: The present study aims to test this hypothesis by using a large scale high resolution intensive care database, the Clinisoft repository. In this database, we have information on \>60 000 patients from three different hospitals and five ICUs, during the years 2005 up until today. The repository will be crossmatched, using the unique Swedish national ID number, with hospital records; to gather information on preexisting illnesses, chronic medication and post-ICU outcomes. It is likely that over 5%, more than 3000 patients, have been treated with RRT. We will categorize these patients into "early" and "late" groups using both biomarker data and clinical data. Importantly, early and late RRT can be categorized using biomarkers, like urea and creatinine; using degree of fluid accumulation, by level of pH in blood and just by using hours-days after ICU admission. All possible definitions of early/late RRT initiation can be tested in this study. Outcomes: Our primary outcome is 90 day mortality. Secondary outcomes include: mortality at 30, 60, 180 and 365 days. Two- and three year mortality. Morbidity, measured as end-stage renal disease (ESRD) for 90-day survivors. ICU length of stay, hospital length of stay.

The goal of this clinical trial is to compare trastuzumab deruxtecan (T-DXd) to standard preoperative treatment in patients with non-metastatic HER2-positive breast cancer. The main questions it aims to answer are: * is T-DXd more effective than standard preoperative treatment? * are there markers in the tumor or blood of patients with HER2-positive breast cancer that can help us predict response to treatment? Participants will be divided into two groups, where one group will be treated with three courses of T-DXd and the other group will be treated with three courses standard of care treatment. Thereafter, further treatment will be decided by the tumor's molecular subtype.

The aim of this study is to investigate when critically ill patients transition from a non-suppressible catabolism to a normal response to feeding. Endogenous production of glucose, fat and protein will be studied on a minimum of two occasions in mechanically ventilated ICU patients, in a fasted state and during parenteral nutrition. Substrate kinetics are estimated by a tracer dilution method using infusions of isotopically labeled glucose, glycerol and phenylalanine. Blood sampling for metabolomics analysis will be performed to elucidate potential biomarkers indicating an anabolic response to nutrition.

ICU patients are recruited after at least 5 days treatment with continuous renal replacement therapy. Blood samples are drawn at time of recruitment and then every 3-5 days until ceseation of renal replacement therapy. Samples will be analyzed for concentrations of trace elements, vitamins and amino acids. 10 adult ICU patients treated for two weeks without renal replacement therapy will be sampled at one time point to serve as controls.

Lactate kinetics will be studied in hospitalized septic patients using a bolus injection of stable isotopically labeled lactate.

The goal of this prospective observational cohort study is to compare health related quality of life in patients with abdominal aortic aneurysms treated by either standard or complex EVAR (endovascular aneurysm repair) devices. The main questions it aims to answer are: * Compare differences between the physical scores from the preoperative to the postoperative settings between patients treated with standard EVAR vs non-standard endovascular aortic repair (F-/BEVAR) * To compare long-term physical scores postoperatively between patients treated with standard EVAR vs non-standard endovascular aortic repair (F-/BEVAR) at one year. * To explore at which time points (if ever) patients treated with standard-EVAR and nonstandard endovascular aortic repair (F-/BEVAR) have restored or normalized physical scores measured by SF-12, measured at 30 days, 6 months, 1 and 3 years. Participants will be asked to fill out forms pre- and postoperatively with regards to health related quality of life. The different groups for comparison will be either standard EVAR for infrarenal aortic aneurysms or complex EVAR (fenestrated or branched) for paravisceral aortic aneurysms (PVAAA).

The goal of this clinical trial is to compare four different methods of reducing heart rate before cardiac imaging. The diagnostic imaging technique used in this study is called Computed Tomography (CT) of the coronary vessels (CCTA). Globally, approximately one-third of patients experience heart-related conditions. Because the heart is a moving organ, imaging presents challenges. A higher heart rate requires increased scanning power, which results in more images and, in some cases, higher radiation exposure that may be harmful. To address this issue, beta-blocker medication is administered before the examination to lower the heart rate. This medication can be given orally, intravenously, or both. While this approach is effective, the most optimal method remains uncertain. The objectives of this study are: * To determine whether oral administration of beta-blockers is as effective as intravenous administration in maintaining a stable heart rate during CT imaging. * To assess whether listening to music during the procedure improves patient comfort and overall experience. Participants will: * Be randomly assigned to one of four groups: * One group will receive beta-blocker medication orally. * Another group will receive beta-blocker medication intravenously. * One group will listen to music during the procedure. Participants will report their sensations and experiences before, during, and after the examination. The study investigators will compare the effectiveness of oral and intravenous beta-blockers, as well as the impact of music, in terms of: * Heart rate stability and reduction. * Participant-reported comfort and overall experience.

NEEDS is a pragmatic open-label, randomised, controlled, phase III, multicenter trial with non-inferiority design with regard to the first co-primary endpoint overall survival and superiority for the experimental intervention definitive chemoradiotherapy. A second co-primary endpoint is global health related quality of life (HRQOL) one year after randomisation. A third co-primary endpoint is eating restictions one year after randomisation. The aim is to compare outcomes after neoadjuvant chemoradiotherapy with subsequent esophagectomy to definitive chemoradiotherapy with surveillance and salvage esophagectomy as needed in patients with resectable locally advanced squamous cell carcinoma (SCC) of the esophagus, with the aim to provide generalisable guidance for future clinical practice.

To evaluate tumor response, survival and adverse effects after precision radiotherapy (SBRT) in melanoma patients with ongoing PD-1 inhibitor treatment that have tumor progression.

ICU patients treated with continuous renal replacement therapy is recruited prior to start of treatment. Blood samples are drawn and then dialysis start without amino acid supplementation. After a few hours samples are drawn from blood and dialysate. Then patients are given amino acid supplementation (33.5g/24hrs) for 20-24 hours. New samples are drawn and amino acid supplementation is increased to 67g/24hrs and new samples are drawn after additional 24 hours. Then CRRT will continue with the full amino acid supplementation (standars of care).

This study aims at determining whether diaphragm ultrasound examining diaphragm thickening fraction, excursion and density before and after surgery can predict respiratory complications in the postoperative period. Patients scheduled for major elective abdominal, pelvic or vascular surgery will be included in the study and diaphragm ultrasound is performed before surgery and after surgery in the postoperative ward. Physiological parameters, laboratory parameters, data on surgery and anesthesia and comorbidities will be registered. Complications such as pneumonia, desaturation, need for intubation and other respiratory events up to 30 days will be registered and later correlated with the diaphragm measurements.

Acute Achilles tendon rupture (ATR) is an injury that is commonly associated with complications, such as blood clotting, muscle loss and tendon lengthening, all of which affect the long-term outcome and return to sports. These complication are related to the treatment of ATR with lower leg immobilization in a boot. The investigators aim to demonstrate that an intervention with calf neuromuscular electrical stimulation (C-NMES) during leg immobilization after ATR can 1) reduce blood clots, 2) lower the degree of muscle loss, 3) decrease tendon lengthening and 4) improve long-term outcome.

A biobank within the Swedish national heart failure quality registry SwedeHF.

Ablative treatments are believed to have a lower rate of complications, shorter hospital stays, and fewer interventions with benign PAD compared to partial nephrectomies in small kidney cancer lesions. The purpose of the study is to compare complications, the frequency of residual tumors, impact on kidney function, differences in quality of life, and health economic factors in a randomised study. We will also compare the oncological outcomes, including survival and recurrence of kidney cancer.

The goal of this study is to investigate the hemostatic balance in children with acute lymphoblastic leukaemia (ALL) treated according to the ALLTogether1 protocol with focus on the early treatment period including concomitant use of steroids and asparaginase. The investigators aim to determine if complement proteins or microparticles can be used as clinically relevant predictive or diagnostic biomarkers for thrombosis and if global hemostatic assays can predict bleeding or thrombosis. Characterization of proteins connected to hemostasis before and during ALL treatment may provide pathophysiological insights regarding ALL- and treatment related coagulopathy. The ultimate goal of the study is to minimize the morbidity and mortality related to thrombosis and bleeding complications in children with ALL. Several pediatric oncology centers in Sweden will be participating in this study, which will enroll approximately 100 pediatric patients.

The goal of this interventional study is to evaluate if pre-emptive intervention using Azacitidine and / or donor lymphocytes or tapering of immune suppression in measurable residual disease (MRD) positive subjects can prevent clinical relapse. Participants will undergo MRD surveillance and be subjected to intervention in case of MRD positivity. Results will be compared with NMDSG14B, part one, in which MRD was analyzed in included patients without recieving intervention.

The goal of this clinical trial is to learn evaluate the safety and efficacy of the addition of radiation therapy to all tumour lesions, to first line medical treatment with alectinib in non-small cell lung cancer harbouring ALK-rearrangements. The main aims of the trial are to evaluate: * if the treatment combination is safe * if the treatment combination can inhibit progression Participants who have responded to 1st line alectinib will be treated with consolidation radiation therapy to all remaining tumour lesions while continuing on alectinib until disease progression, unacceptable toxicity or another discontinuation criterion is met.

The study will compare two forms of advice regarding physical activity for patients hospitalized with cirrhosis that are preparing for leaving the hospital. One arm consists of current standard of care: simple oral advice on exercise. One arm instead gives patients a structured but simple paper template on physical activity.

The aim is to assess the efficacy and specific safety in an observational study of patients with Chronic hepatitis D (CHD) with prospective follow-up, with antiviral treatment of 2 mg Bulevirtide (BLV) +/- PEG-IFNα-2a and +/- NA given as part of the patient's routine medical care. Also, explorative endpoints of biomarkers in peripheral blood, saliva, fecal sample and/or intrahepatic markers/signatures, and quality of life outcomes will be assessed.