Clinical trials

The goal of this clinical trial is to learn if the surgical method with total joint arthroplasty, (TOUCH joint prosthesis), is as good as or better than the traditional surgical method, trapezectomy, to treat thumb base joint osteoarthritis. The main questions it aims to answer are: Does surgery with total joint arthroplasty provide better power grip and pinch grip strength compared to traditional surgery? What is the long-term risk of complications for both methods? Which method is more cost-effective for the healthcare system? Researchers will compare total joint arthroplasty (TOUCH) to trapezectomy (a procedure where a bone in the thumb base is removed) to see which method provides the best results for the patient. Participants will: Be randomized to undergo either an operation with total joint arthroplasty or a trapezectomy. Undergo an initial evaluation and a health economic cost analysis after one year. Attend follow-up checkups at 2, 5, and 10 years post-surgery to evaluate long-term function and the durability of the prosthesis.

The EMBER protocol is a health care method that is designed to increase resilience, in order to improve well-being and overall health in women who have experienced violence by a partner. This study explores whether the EMBER intervention works in this way. Eight participants will take part in the EMBER program and complete questionnaires every week during the intervention. The researchers will compare the timeline for the intervention to how resilience levels change. They will also check whether changes in resilience are linked to changes in health and well-being.

The EMBER-protocol is an intervention used at the NCK clinic at Uppsala University Hospital with the purpose of helping women utilize their resilience and strengths in order to recover after intimate partner violence. This study is conducted in order to explore how health and resilience changes during the course of the EMBER-intervention. The participants are asked to complete questionnaires before, during and after the intervention.

The goal of this observational study is to understand the genetic and molecular risk factors for developing critical illness in adult intensive care unit (ICU) patients in Sweden. The main questions it aims to answer are: Which genetic variants are associated with increased risk of critical illness from conditions such as infections, sepsis, and organ failure? Can circulating proteins and metabolites mediate the effect of genetic risk factors on the severity of illness? Participants will: Provide blood samples at ICU admission and again 3-6 months after discharge Consent to genetic analysis and data linkage with national health registries Have their ICU treatment and outcomes followed using registry and clinical data This study aims to build a national infrastructure for rapid sample collection and analysis that can also support research in future pandemics.

This project aims to conduct an international, prospective, multicentre, observational study to determine the incidence of Postoperative Acute Kidney Injury (PO-AKI) in hospitalized children after noncardiac surgery. Urinary biomarkers are intended to be evaluated as predictors of PO-AKI in the same subjects. The study employs modern standardized classifications for AKI to comprehensively address the issue of PO-AKI in children. Describing the incidence and identifying risk factors for PO-AKI will play a crucial role in developing preventive strategies aimed at reducing associated mortality and morbidity. Furthermore, investigating the relationship between urinary biomarkers of renal injury and PO-AKI will provide valuable insights into assessing postoperative renal function in paediatric patients, especially when repeated blood sampling is not feasible.

PROSAP-A is a perioperative randomized, controlled trial with a 12-month follow-up period after total knee arthroplasty (TKA) or total hip arthroplasty (THA), aiming to investigate both acute and long-term postoperative effects of preoperative sleep-promotion. Participants with clinically significant insomnia symptoms will be randomized to a brief, hybrid version of cognitive behavioral therapy for insomnia (CBT-I) or sleep education therapy, administered over a 4-week period, prior to surgery. The primary objective is to evaluate effects of preoperative sleep-promotion on acute postoperative pain control. Secondary objectives include evaluation of postoperative sleep, recovery, mental health, cognitive function and alterations in blood biomarkers.

This observational study aims to evaluate skin conductance monitoring as a continuous method for pain assessment in postoperative neonates. Pain assessment in newborns is challenging due to their inability to communicate, and current methods rely on intermittent observational scales such as the Neonatal Pain, Agitation and Sedation Scale (N-PASS) in combination with physiological parameters. Skin conductance reflects sympathetic nervous system activity and provides a continuous, objective measure of stress and pain. This study will investigate the correlation between skin conductance measurements and standard clinical pain assessment tools (N-PASS and vital parameters), as well as explore the potential analgesic effect of skin-to-skin care. The study is conducted in a neonatal intensive care unit (NICU) setting where all monitoring and treatments are part of routine clinical care.

At Uppsala University Hospital, there is an outpatient clinic for women subjected to intimate partner violence. In order to explore how patients experience the biopsychosocial resilience-based intervention in use at the clinic and how well the intervention fits the needs of the patients, 30 patients from different stages of their contact at the clinic and with diverse life situations and background are enrolled. The researchers will carry out individual in-person interviews, each lasting approximately 60 minutes, based on a semi-structured set of questions. The questions concern the participant´s life situation, resilience and self-perceived needs, how well the intervention has met those needs and how it was perceived by the participant. The interviews are audio-recorded and transcribed verbatim for thematic analysis.

Shame is a normal emotion that people sometimes have. Experiencing a lot of shame has however been found to have a link to ill mental and somatic health. Therefore it is of interest to have a brief way of measuring shame. External and Internal shame scale (EISS) is a questionnaire with 8 items that is available in several languages, but not yet in Swedish. The researchers have translated it to Swedish and will investigate how well the Swedish version works for measuring shame. 300 participants are enrolled via social media and asked to complete the EISS as well as two other scales for comparison. Participants are also asked about their age and gender. In addition 50 participants will be recruited from an outpatient clinic in order to check how the scale works in clinical settings. The researchers will use the answers to statistically calculate the scientific properties of the EISS.

The HiHat trial is a Phase 2 study aimed at evaluating the safety and feasibility of sequential treatment with rituximab and cladribine in patients with relapsing-remitting multiple sclerosis (RRMS). The study follows a prospective, open-label, single-arm design, with 60 RRMS patients receiving both treatments in a controlled regimen: two cycles of rituximab (1,000 mg each, biweekly) followed by two cycles of cladribine (30 mg per cycle for three days per cycle) spaced one month apart. Participants are monitored over 24 months through clinical assessments, MRI, and biomarker analyses. The primary objective is to evaluate whether the rate of serious adverse events (SAE) is acceptably low. Secondary objectives include assessing impacts on MRI lesion count, relapse rates, disability progression, quality of life, and safety.

1. Rational Every year, around 5,000 people in Sweden are diagnosed with malignant skin melanoma. In the early stages of malignant skin melanoma, the chance of cure with surgery is very good. At a later stage, when the melanoma has become thick and/or has spread, the risk of recurrence is greater despite radical surgery. Therefore, in these cases (even in cases of recurrence after radical surgery), additional treatment with immunotherapy is often given, as it has been shown to reduce the risk of recurrence. Immunotherapy is given for one year based on previous research studies, but it has not been investigated whether a shorter treatment period has the same effect. The hypothesis is that six months of treatment is equally effective, which would have several advantages. The main advantage of a shorter treatment period is that the risk of severe side effects is reduced. A shorter treatment period also means fewer hospital visits for patients. In addition, significant drug costs and other healthcare resources could be saved. 2. Aim/objective The aim of the study is to investigate whether 6 months of treatment with immunotherapy, in addition to radical surgery, for malignant skin melanoma at high risk of recurrence, is as effective in preventing recurrence as 12 months of treatment. Secondary objectives: To investigate overall survival after 6 versus 12 months of treatment with immunotherapy. To investigate the health economic effects of a shorter treatment. 3. Primary endpoints The two primary endpoints of the study are relapse-free survival (RFS) and distant metastatic-free survival (DMFS) and they will be analyzed for the first time in the interim analysis conducted after 2/3 of the estimated number of patients have been included in the study. 4. Secondary outcome measures Overall survival will be analyzed for the first time in the interim analysis. Health economic calculations are planned only at the final stage of the study. 5. Study design This is a randomised phase 3 study, with the aim of showing that treatment in the experimental arm (6 months of immunotherapy) is not inferior to the treatment in the standard arm (12 months of immunotherapy). Patients will be followed up to five years. The visits in the study follow clinical routine. 6. Study population Patients aged ≥18 years undergoing radical surgery for stage IIb-c, III or IV cutaneous malignant melanoma, with a WHO general condition score of 0-1 and deemed tolerable to immunotherapy. 7. Study treatment The study treatment consists of immunotherapy according to clinical routine, currently nivolumab or pembrolizumab given intravenously for either 6 months (experimental treatment) or 12 months (standard treatment). For patients receiving neoadjuvant treatment (additional treatment before surgery), the neoadjuvant treatment time is added to the adjuvant treatment time (additional treatment after surgery) to give a total treatment time of 6 or 12 months. Treatment is followed up according to routine, with imaging (CT or PET-CT) at baseline and after 6 months and at an additional time beyond clinical routine, after 36 months, as well as medical examination at baseline, 6, 12, 18, 24 and 36 months. In case of any signs of relapse, additional examinations are performed as needed. If relapse is detected, the patient is discussed at a local multidisciplinary conference to select the best available treatment for each patient. All study patients are followed for survival status for up to five years. 8. Risk-benefit and ethical issues If this study shows that a shorter treatment period is as effective as the current one-year treatment, it would greatly benefit patients by reducing the risk of side effects and reducing the number of hospital visits. It would also save healthcare resources, which could then be used in other areas. The Swedish Melanoma Patient Association (Melanompatientföreningen) has been consulted and is positive about the study, however they expect that patients may be reluctant to participate for fear of receiving inferior treatment. However, none of the pivotal studies conducted to date have shown that adjuvant systemic treatment of patients with malignant melanoma significantly prolongs overall survival, but its routine use is based on prolonged relapse-free survival. In addition, a recent cohort study indicated no survival benefit after the introduction of immunotherapy. To ensure that the experimental arm is not clearly inferior to the standard arm, an interim analysis will be conducted in this study (see above). It is worth mentioning that similar studies to Grand SLAM have been conducted in breast and colon cancer where additional treatment after surgery has been introduced as it not only reduces the risk of recurrence but also prolongs overall survival. These studies have shown that shorter treatment is equally effective.

This prospective multicenter observational cohort study evaluates robotic-assisted pedicle screw placement compared with non-robotic-assisted techniques in spinal surgery. Primary objectives include screw placement accuracy, operative learning curve, and reoperation rate within 2 years.

The goal of this clinical trial is to learn whether improving caregivers' mental health and parenting practices can enhance child wellbeing among Congolese refugee families living in the Nyarugusu Refugee Camp, Tanzania. The WEMA trial ("Wellbeing through combined Evidence-based tools for Mental health and Attuned parenting") is a three-arm, family-level cluster-randomized, controlled superiority trial involving 324 families (approximately 648 children aged 7-10 years and their two primary caregivers). Participants and intervention facilitators will know which program a family receives, but outcome assessors (enumerators) will not know group assignment. The main questions it aims to answer are: * Does Self-Help Plus (SH+), a World Health Organization (WHO) group stress-management program, improve children's emotional and behavioral functioning at 12 months post-intervention, compared with usual care? * Does adding Interaction Competencies with Children for Parents (ICC-P), a participatory parenting program, after SH+ further improve children's emotional and behavioral functioning at 12 months post-intervention, compared with SH+ alone? Researchers will compare (1) Usual Care, (2) SH+, and (3) SH+ followed by ICC-P to see whether SH+ improves outcomes versus usual care, and whether SH+ followed by ICC-P provides additional benefits beyond SH+ alone. Participants will: * Be assigned by chance by family clusters to one of three groups: Usual Care, SH+, or SH+ followed by ICC-P. * Receive either (a) information about available psychosocial and mental health services (Usual Care), (b) SH+ (five group sessions delivered by trained non-specialists), or (c) SH+ followed by ICC-P (a four-day participatory parenting training to strengthen positive parenting and reduce harsh discipline). * Complete study assessments at baseline, 3 months, and 12 months post-intervention. The primary outcome is children's emotional and behavioral functioning, measured using the Pediatric Symptom Checklist-17 (PSC-17) at 12 months post-intervention. Secondary outcomes include children's wellbeing and quality of life, as well as caregivers' mental health, well-being, and parenting practices. Additional exploratory outcomes will also be assessed, including measures collected from caregivers and behavioral tasks with children. The trial is implemented by Uppsala University in collaboration with the Dar es Salaam University College of Education (DUCE) and partners, with funding from the Swedish Research Council (grant no. 2022-02476).

Sleep and metabolism are closely interconnected, and emerging evidence suggests that dietary composition may influence both sleep quality and key physiological functions such as glucose regulation, cardiovascular activity, and hormonal signaling. This study aims to investigate how a Western-style unhealthy diet versus a healthier, fiber-rich diet affects objective and subjective sleep measures, 24-hour physiological parameters, and a range of biomarkers related to cardiometabolic, neurodegenerative, and gut microbial function.

The goal of this observational study is to identify biomarkers of treatment-induced brain injury in children treated for primary brain tumors. The main question it aims to answer is: Can investigators identify sensitive plasma biomarker(s) of treatment-induced brain injury in children with primary brain tumors? Researchers will compare results between different treatment modalities (surgery, chemotherapy, radiation versus radiation-naive) and a healthy age- and sex-matched control population, to identify treatment-specific biomarkers. Participants will provide plasma samples at the following time points: before surgery, 1-2 weeks after surgery, as well as at 3-, 6-, 12-, 18-, 24-, and 36 months after surgery. Participants who receive radiation treatment will also provide plasma samples before and during treatment (approximately every 2 weeks). Where possible, plasma samples are also collected before the start of any new treatment (e.g., chemotherapy). Healthy controls will provide samples once.

Pancreatic neuroendocrine tumours (pan-NETs) are neoplasms arising from the endocrine cells of the pancreas. Although pan-NET are quite rare, the incidence is on the rise and together with other abdominal neuroendocrine tumours an approximate incidence in Sweden would be 850 patients per year extrapolating from Norwegian data. Pan-NET are divided into symptomatic hormone producing tumours (such as insulinomas/glucagonomas/VIPomas) or non-functioning tumours that often are asymptomatic. As early symptoms often are lacking in non-functioning-pan-NET, many patients present with distant metastases and are thus beyond a curative surgical approach at the time of diagnosis. Metastatic non-functioning pan-NETs present a significant challenge and the optimal management remains a subject of debate. This is a prospective, two armed, parallel, randomised, controlled, international multi-centre study, aiming to investigate if a near-total tumour debulking (intervention) in metastatic (stage 4) GI-WHO grade 1-2 pan- NET, with or without oncologic treatment, is superior to oncologic treatment alone (control), with regards to overall survival, health-related quality of life, participant performance status, time until hospitalisation, adverse event characteristics and cost in the short and long term.

The goal of this trial is to evaluate an open TAP-block vs continuous administration of local anestetic via a wound catheter for postoperative pain management in patients 1-15 years of age undergoing open abdominal surgery.

The goal of this observational study is to learn about the influence of extracellular water on volume status in adult sepsis patients presenting with hemodynamic instability. The main question it aims to answer is: • Can measurement of extracellular water (MoistureMeterD, Delfin Technologies Ltd, Kuopio, Finland) contribute to the description of hemodynamic instability in adult sepsis patients. Patients with sepsis admitted to intensive care will receive standard care with the addition of measurement of extracellular water.

Acute kidney injury (AKI) affects more than 50% of patients admitted to the intensive care unit. The most common underlying cause is sepsis. Severe AKI in combination with sepsis is associated with high mortality. The mechanisms for sepsis-induced AKI are largely unknown. Our hypothesis is that the inflammatory response to an infection cause collateral damage to host tissue and contributes to the development of AKI. In this study we want to investigate the presence of novel inflammatory mediators in patients with sepsis, patients subjected to major surgery (sterile inflammation) and non-inflamed patients and correlate their levels with the risk for AKI.

The goal of this clinical trial is to investigate Negative Pressure Wound Therapy (NPWT) in adults undergoing emergency laparotomy. The main question it aims to answer is: Does NPWT decrease wound complications? Researchers will compare it against regular dressings to see if NPWT is superior.

A multicentre multinational RCT to investigate whether non-surgical treatment is non-inferior to surgical treatment for displaced extraarticular lateral clavicle fractures in adults.

The goal of this clinical trial is to learn if oral treatment with pivmecillinam is effective to treat febrile urinary tract infections in adult patients. Hospitalized patients who have received 2-4 days of intravenous antibiotic therapy for febrile urinary tract infections, and have responded to treatment, will be randomized to either pivmecillinam or standard treatment (other oral or intravenous antibiotics). The main question the study aims to answer is if oral follow-up with pivmecillinam is as effective as standard treatment. Patients will be evaluated for clinical response (resolution of fever and urinary tract symptoms) and microbiological response (no growth of bacteria in urine) 7 and 28 days after the end of treatment. Patients will also be asked about side effects. Some of the participants will also be examined for changes in the gut microbiome and drug exposures in blood and urine. Participants will: 1. Keep a patient diary to record antibiotic intake, body temperature, urinary tract symptoms, and suspected side effects until 7 days after end of treatment. 2. Participate in phone interviews 7 and 28 days after end of treatment to assess clinical response. 3. Provide urine samples 7 and 28 days after end of treatment to evaluate microbiological response. 4. A subgroup (60 patients) will provide fecal samples at five time-points over three months to assess antibiotic-induced changes in the gut microbiome. 5. A subgroup (30 patients) treated with to pivmecillinam will provide blood and urine samples to determine the pharmacokinetics of mecillinam during one dosing interval.

Infectious endocarditis (IE) is associated with mortality rates of 10-12%. Adequate antibiotic therapy is crucial for survival and is administered in high doses due to the severity of the disease. In most cases, beta-lactam antibiotics (e.g. ampicillin, penicillin G, cefotaxime or cloxacillin) are employed. A number of patient characteristics, such as age, body weight, and renal function) influence the pharmacokinetics of these drugs. Yet, the interindividual variability is poorly understood meaning that a large proportion of patients are at risk of subtherapeutic or excessive drug concentrations that might result in treatment failure or side effects, respectively. In the present study, data will be collected on antibiotic concentrations in patients treated with beta-lactams for infectious endocarditis as well as patient characteristics and treatment outcomes. A mathematical model will be developed to determine which patient factors determine drug pharmacokinetics. Based on this model, predictions will be made by mathematical simulations on which dosing regimens are optimal for individual patients to ensure therapeutic and non-toxic drug concentrations. In total, 150 patients will be included at four University Hospitals in Sweden; Uppsala University Hospital, Sahlgrenska University Hospital in Gothenburg, Skåne University Hospital in Lund and Karolinska University Hospital in Stockholm. Following informed consent to participate blood samples will be collected at 6 time-points during a dose interval and then at 3 time-points weekly during the full treatment episode (maximum 6 weeks).

This study compares three different online psychological treatments for people with clinical burnout (stress-related exhaustion) who are on sick leave or have major difficulties coping at work or in daily life. Many patients with burnout receive broad, recuperation-focused interventions (rest, stress reduction, lifestyle changes), but there is still no clearly evidence-based treatment or agreed clinical model. It is also known that returning to work can be difficult, and there is a need for more structured support. In this trial, 210 adults in Sweden with clinical burnout will be randomly assigned to one of three 10-week, internet-based treatments: Online Acceptance and Commitment Therapy (ACT) A structured, values-based CBT approach that focuses on helping participants clarify what matters to them, relate differently to difficult thoughts and feelings, and gradually re-engage in meaningful activities despite exhaustion. Online Recuperation-focused treatment An active comparison condition that emphasizes rest, recuperation, and healthy daily routines. It provides psychoeducation and practical tools for sleep, relaxation, physical activity, pacing, and balance in everyday life, but does not include ACT-specific methods such as exposure or values work. Online ACT plus Vocational Support The same ACT program as in group 1, together with three additional sessions with a licensed psychologist focused on work. These sessions help the participant identify work-related barriers, plan a gradual return-to-work (RTW), and formulate a written RTW plan that can be shared with the employer and treating physician. All three treatments are delivered via a secure digital platform. Participants work through weekly online modules, receive written feedback from a therapist, and have three video sessions during the 10-week period. Clinical psychology students in their final semester deliver the ACT and recuperation treatments, and licensed psychologists deliver the ACT + vocational support condition. The study has two primary aims: 1. to test whether online ACT reduces self-rated burnout symptoms more than the recuperation-focused treatment at the end of treatment, and 2. to test whether adding structured vocational support to ACT reduces the total number of registered sick-leave days in the year after treatment, compared with ACT alone. Key secondary outcomes include perceived stress, depression, anxiety, insomnia, everyday memory problems, quality of life, functional impairment, treatment response and remission, treatment credibility and satisfaction, and cost-effectiveness. Outcomes are measured before treatment, weekly during treatment (for selected measures), immediately after treatment, and at 6- and 12-month follow-ups. Sick-leave data are obtained from the Swedish Social Insurance Agency. To be eligible, participants must be 18 years or older, have symptoms consistent with clinical burnout (including pronounced fatigue and reduced stress tolerance after prolonged psychosocial stress), be on at least 25% sick leave or have marked functional impairment due to these symptoms, have a stable occupation or study situation, and be able to read and write Swedish. People with very long sick leave (more than two years), severe psychiatric conditions (such as severe depression, bipolar disorder, untreated PTSD, or psychosis), current substance abuse, or active suicidal ideation will not be included. Potential risks include temporary increases in distress, fatigue, or symptom awareness when working with emotions, behavior change, or work-related issues. Participants are monitored closely through weekly questionnaires and therapist contact. If risk for self-harm or serious deterioration is detected, a licensed psychologist will perform a risk assessment and, if needed, refer the participant to appropriate health care. The hope is that this study will identify effective, scalable, and theory-based online treatments for clinical burnout and clarify whether adding structured vocational support improves long-term work outcomes.

Surgical treatment for idiopathic scoliosis usually involves open surgery from the back (posterior approach). This method corrects the curve and stabilizes the spine using screws and rods, followed by a fusion of the treated segments. The goal is to achieve the best possible alignment of the spine. This type of surgery can be demanding for the body and often requires a longer hospital stay because of tissue damage and pain after the procedure. Traditionally, patients stayed in the hospital for up to a week or more. In recent years, recovery programs such as ERAS (Enhanced Recovery After Surgery) have been introduced. These programs include better pain control, faster mobilization, and improved preparation before surgery. Thanks to these improvements, many patients can now go home one to two days after surgery instead of several days. There has also been a development of minimally invasive surgery (MIS) techniques in spine surgery. These techniques aim to reduce tissue damage and blood loss compared to traditional open surgery. Smaller incisions can lead to less scarring, less pain, and potentially faster recovery. Because scoliosis surgery is complex, it is important to study whether MIS offers the same safety and benefits as traditional surgery. Minimally invasive surgery makes correct screw placement in the curved spine more challenging, as the usual anatomical landmarks are not fully exposed. To ensure accuracy, MIS often uses advanced technologies such as intraoperative 3D imaging or robotic-assisted surgery (RAS). The purpose of this project is to evaluate whether MIS is as safe and effective as traditional open surgery. The study will compare both methods regarding the need for additional surgery, complications, infections, pain, and bone fusion after surgery. It will also examine hospital stay, degree of curve correction, accuracy of screw placement, changes in nerve function during surgery, blood loss, operation time, and patient-reported outcomes. Most existing studies on MIS in scoliosis are based on older or small patient series, and randomized controlled trials are lacking. This research will provide scientific evidence to guide future treatment choices. The aim is to determine whether MIS can deliver the same correction and safety as open surgery while reducing pain, blood loss, and recovery time. If proven effective, these techniques could improve recovery and quality of life for many scoliosis patients.