Konstanz

This study is open to people with idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF). They can only take part if they have completed treatment in a previous study with a medicine called nerandomilast or BI 1015550. The goal of this study is to find out how well people with pulmonary fibrosis tolerate long- term treatment with nerandomilast. The study also tests whether nerandomilast improves lung function and prolongs the time until symptoms get worse, participants need to go to the hospital, or die. Every participant takes nerandomilast as tablets for up to 1 year and 10 months. The participants may also continue their regular treatment for pulmonary fibrosis during the study. Participants visit their doctors regularly. During these visits, the doctors collect information on any health problems of the participants. Participants also regularly do lung function tests.

This non-interventional study aims to provide information on real-world effectiveness, safety and tolerability, management of adverse events, QoL and patient compliance of patients with HR+/HER2- early breast cancer at high risk of recurrence treated with ribociclib in combination with an aromatase inhibitor (AI) ± luteinizing hormone-releasing hormone (LHRH) with curative intent according to the current effective local summary of product characteristics. In order to put the results of patients treated with ribociclib into perspective, socio-economic data, data on QoL and patient compliance will also be collected from patients treated with abemaciclib + endocrine therapy (ET) ± LHRH as described in the current effective local summary of product characteristics. To understand reasons for treatment decision, and to analyze the clinical adoption of ribociclib + AI ± LHRH after EU approval over time, baseline data will be collected from cohorts of ribociclib + AI ± LHRH, abemaciclib + ET ± LHRH, and additionally from patients treated with ET monotherapy ± LHRH and analyzed cross-sectionally. The study is planned to be rolled out into a broad set of German and Austrian breast centers and gynecological practices to describe clinical routine in a representative subset of the local healthcare eco-system. It will gather insights into the potential benefits and risks associated with ribociclib + AI ± LHRH in the adjuvant treatment of HR+/HER2- eBC patients at high risk of recurrence. This knowledge will inform about clinical decision-making and contribute to improved patient outcomes in routine practice.

The aim of the current study is to evaluate the effectiveness and safety of bempedoic acid combined with ezetimibe and either atorvastatin or rosuvastatin (hereafter defined as triple therapy) in a real-world clinical setting. No drug will be administered during this observational study. The primary objective of the study is to evaluate the effectiveness of the triple therapy in terms of LDL-C reduction at 8 weeks. The secondary objectives will include the following: * Goal attainment at 8 weeks and 1 year after start of triple therapy * Effectiveness of triple therapy in terms of LDL-C reduction at 1 year * Effectiveness of adding bempedoic acid to statin and ezetimbe at 8 weeks and 1 year * Effectiveness of adding bempedoic acid/ezetimibe FDC to statin in terms of LDL-C reduction at 8 weeks and 1 year * Changes in laboratory values at 8 weeks and 1 year after start of triple therapy * Adherence to triple therapy treatment * Collection and recording of all adverse events occurred since initiation of triple therapy * MACE-3 and MACE-4 (consisting of non-fatal MI, non-fatal stroke, CV-death, and coronary revascularization (for MACE-4 only)) during the year of follow-up * Treatment changes at LMT initiation and at triple therapy initiation * Treatment pathway from triple therapy initiation to 1-year after start of triple therapy

The purpose of this study is to describe the clinical and health-related outcomes of amivantamab-containing regimens for the treatment of common epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC; most common type of lung cancer) in a real-world setting. Metastatic NSCLC is when this disease spreads to other parts of body. NSCLC may occur due to mutations (changes) in many genes including epidermal growth factor receptor (EGFR).

AZD0292 is a bispecific IgG1k mAb being evaluated for the prevention of exacerbations in bronchiectasis patients chronically colonized with PsA. This Phase IIb study aims to assess the efficacy, safety, and PK of 2 dosage regimens of AZD0292 administered IV, as compared to placebo in participants 12 years of age and older. The primary population of this study will be PsA-colonized NCFBE patients, a bronchiectasis group with frequent pulmonary exacerbations due to chronic PsA airway colonization. These PsA associated pulmonary exacerbations contribute to a decline in lung function, impair quality of life and increase mortality, highlighting the urgent need for effective therapeutic options. To investigate the broader applicability of AZD0292, bronchiectasis patients with CF who are colonized with PsA will be also included as a non-powered exploratory group in this Phase IIb study.

Adults 18 years of age and older or above legal age with lung fibrosis related to systemic autoimmune rheumatic disease can participate in this study. People can only take part if they show no improvement in lung function after standard treatment with immunosuppressant medicine. The main purpose of this study is to find out how a medicine called nerandomilast affects the lungs in people with systemic autoimmune rheumatic disease. Participants are put into 2 groups randomly, which means by chance. One group takes nerandomilast tablets and the other group takes placebo tablets. Placebo tablets look like nerandomilast tablets but do not contain any medicine. Participants take a tablet 2 times a day for at least 26 weeks and up to 1 year. Participants continue immunosuppressant treatment for their underlying rheumatic disease. Participants are in the study for about 7.5 to 13 months depending on when they join the study. During this time, they visit the study site about 9 to 10 times. At study visits, participants have lung function tests. At select visits, chest imaging is performed. Participants fill in questionnaires about their symptoms and quality of life. The results between the 2 groups are compared to see whether the treatment works. The doctors also regularly check participants' health and take note of any unwanted effects.

Originally registered as OBS17104 by Sanofi; transitioned to REGN 05Jul2023. The recruitment period will be 48 months. Data will be collected during routine clinical visits approximately every three months while the patient is on cemiplimab treatment and then approximately every six months for up to 24 months after cemiplimab discontinuation. Patients will be followed from cemiplimab treatment initiation until death, loss to follow-up, study withdrawal, or to the end of the study period (72 months after study launch), whichever occurs first.

The MINERVA Trial aims to evaluate safety, efficacy and quality of life (QoL) for the combination of Abemaciclib with an Aromatase Inhibitor or Fulvestrant in pre- and postmenopausal patients with metastatic hormone receptor positive HER2 negative breast cancer in the first line setting. Side effect monitoring and patient reported outcomes will be captured using the web- and app-based CANKADO digital health application. Via this user-friendly tool the patients can document their therapy side effects (e.g. diarrhea) and outcomes on a day-to-day basis. The capturing of side effects using the digital health application will be done additionally to the regular AE documentation. Furthermore, translational research objectives of this trial include the investigation of biomarkers (ct-DNA, germline DNA) to evaluate whether they can give insights into the reasons for response, intrinsic or acquired resistance to the combined endocrine

The PTSD-iMPACT is designed to assess the severity of PTSD-related functional impairment across specific activities and tasks in multiple life domains. The development of the PTSD-iMPACT followed a two-phase process. First, a systematic review was conducted to examine how existing PTSD-specific instruments, diagnostic interview modules, and general measures of functional impairment assess PTSD-related impairment in youth. The review revealed considerable heterogeneity in the domains assessed, frequent reliance on dichotomous response options, inconsistent scoring procedures, and a general lack of psychometric validation. Many instruments assessed functioning only at a global level, without capturing the specific nature or severity of difficulties within each domain. Furthermore, most relied on face validity and lacked demonstrated content validity, highlighting the need for a more methodologically sound tool. In the second phase, qualitative interviews and focus groups were conducted (Cantonal Ethics Committee Zurich, Switzerland; BASEC-ID 2023-01290) with trauma-exposed children and adolescents (aged 7-18) who presented with at least moderate PTSS, as well as caregivers of children aged 1-18 with similar symptom profiles. Participants were recruited through clinical and social service settings. Data were analyzed using qualitative content analysis to identify relevant domains of functioning and specific challenges within those domains affected by PTSS. This conceptual framework informed item generation for the PTSD-iMPACT. Item refinement was carried out with input from clinical and research experts. The final instrument includes both a self-report and caregiver-report version for children and adolescents aged 7-18, as well as a caregiver-version for children aged 3-6. It is designed to enhance clinical decision-making, improve diagnostic accuracy, and support outcome monitoring across diverse international contexts. To ensure that the PTSD-iMPACT functions as a psychometrically sound and clinically meaningful assessment tool, validation across both clinical and non-clinical populations is essential and is therefore carried out in the present study. This process will allow for the evaluation of sensitivity, specificity, and broader applicability across varying levels of functional impairment, thereby supporting its use in both research and routine clinical practice. The primary outcome will be the PTSD-iMPACT. The secondary outcomes for 7-18 year old children and adolescents include sociodemographic information, PTEs, PTSD, depression, anxiety, adjustment disorder, level of functioning, health-related quality of life, and regulation of emotional expression. The secondary outcomes for 3-6 year old children (caregiver-report) include sociodemographic information, PTEs, PTSD, depression, anxiety, oppositional behavior, adjustment disorder, stressor-related thoughts and worries, and health-related quality of life. Table 1 provides an overview of the constructs assessed and corresponding instruments used across participant groups. Hypothesis and primary objective The overall aim of this study is to evaluate the psychometric properties of the PTSD-iMPACT questionnaire in trauma-exposed children and adolescents. The specific aims of the present project are as follows: 1. To examine the reliability of the PTSD-iMPACT for children and adolescents aged 7 to 18 years. This includes the internal consistency of the self- and caregiver report, as well as the test-retest reliability of the PTSD-iMPACT, and the CATS-2 with a time span of two weeks. Hypothesis 1a: Internal consistency: We assume that the items of the PTSD-iMPACT self-report (7-18y) positively correlate with each other, as well as the items of the PTSD-iMPACT caregiver report (7-18y). Hypothesis 1b: Test-retest-reliability: We assume a positive correlation between the results of the first and second time of measurement of the PTSD-iMPACT (7-18y), as well as the CATS-2. 2. To examine the validity of the PTSD-iMPACT for children and adolescents aged 7 to 18 years, including the construct validity (convergent and divergent validity), the criterion validity (concurrent and predictive validity) and the factorial validity. Furthermore, we aim to determine an optimal cut-off value. Hypothesis 2a: Construct validity: We assume stronger positive correlations between the PTSD-iMPACT (7-18y) and the PTSD-specific instrument CATS-2 compared to its correlations with measures of general emotional and behavioral problems (IDQ, IAQ). Additionally, we expect the KIDSCREEN-10, which measures health-related quality of life, to show negative correlations with PTSD-iMPACT (7-18y). While not a direct measure of functional impairment, it captures aspects of well-being that are likely influenced by PTSD-related difficulties in daily life. Hypothesis 2b: Concurrent validity: We assume that the results of the PTSD-iMPACT (7-18y) positively correlate with the results of the Work and Social Adjustment Scale for Youth (WSAS-Y) and the universal 0-100 rating question "To what extent have the symptoms affected your child in daily life?". Hypothesis 2c: Predictive validity: We hypothesize that results of the PTSD-iMPACT (7-18y) differ between individuals with a normal, moderate, elevated and high PTSD symptomatology. Hypothesis 2d: Factorial validity: We assume that the theoretically and empirically derived structure of the PTSD-iMPACT (7-18y) is plausible (the factors reflect the subscales and the items of each subscale load onto their respective factors). 3. To examine the reliability of the PTSD-iMPACT for children aged 3 to 6 years. This includes the internal consistency of the caregiver report, as well as the test-retest reliability of the PTSD-iMPACT, and the CATS 3-6 with a time span of two weeks. Hypothesis 3a: Internal consistency: We assume that the items of the PTSD-iMPACT self-report (3-6y) positively correlate with each other, as well as the items of the PTSD-iMPACT caregiver report (3-6y). Hypothesis 3b: Test-retest-reliability: We assume a positive correlation between the results of the first and second time of measurement of the PTSD-iMPACT (3-6y), and the CATS 3-6 4. To examine the validity of the PTSD-iMPACT for children aged 3 to 6 years, including the construct validity (convergent and divergent validity), the criterion validity (concurrent and predictive validity) and the factorial validity. Furthermore, we aim to determine an optimal cut-off value. Hypothesis 4a: Construct validity: We assume stronger positive correlations between the PTSD-iMPACT (3-6y) and the PTSD-specific instrument CATS 3-6, compared to the correlations between results of the PTSD-iMPACT (3-6y) and questionnaires assessing general emotional and behavioral problems (CBCL subscales: anxiety, depression, oppositional behavior). Additionally, we expect the Pediatric Quality of Life Inventory (PedsQL) \[22\], which measures health-related quality of life, to show negative correlations with PTSD-iMPACT. Hypothesis 4b: Concurrent validity: We assume that the results of the PTSD-iMPACT negatively correlate with ad the universal 0-100 rating question "To what extent have the symptoms affected your child in daily life?". Hypothesis 4c: Predictive validity: We hypothesize, that results of the PTSD-iMPACT (3-6y) differ between individuals with a normal, moderate, elevated and high PTSD symptomatology. Hypothesis 4d: Factorial validity: We assume that the theoretically and empirically derived structure of the PTSD-iMPACT (3-6y) is plausible. Statistics and Methodology After the completion of data collection and prior to the statistical analysis of reliability and validity, a final integration of all measurement data from all participating centers will be conducted. Statistical analyses will be performed using R, SPSS and Mplus. All statistical analyses will be conducted using a two-sided significance level of α = 0.05. A minimum of 100 trauma-exposed participants per clinical cohort is deemed required. Statistical analysis for the PTSD-iMPACT (7-18 years) validation • Sample and items descriptives: Item description, item means, standard deviations, skewness, kurtosis, and range for both self- and caregiver report. Reliability * Internal consistency: Cronbach's alpha and McDonald's omega for PTSD-iMPACT (self- and caregiver report). * Test-retest reliability: The Intraclass Correlation Coefficient (ICC) will be calculated for PTSD-iMPACT, and the CATS-2. Validity Construct Validity: * Convergent validity: Correlations with the PTSD-specific instrument CATS-2, and the health-related quality of life measure (KIDSCREEN-10). * Divergent validity: Correlations with questionnaires assessing general emotional and behavioral problems (IDQ, and IAQ). Criterion Validity: * Concurrent validity: Correlations with the WSAS-Y. The universal 0-100 rating question will be used as an external criterion. * Predictive validity: Differentiation between individuals with a normal, moderate, elevated and high PTSD symptomatology (Mann-Whitney U test, Cohen's d). ROC analyses will be conducted to determine diagnostic accuracy (sensitivity, specificity). The optimal cut-off value will be determined using the Youden Index. Factorial Validity: • Confirmatory Factor Analysis (CFA): Examination of the theoretically and empirically derived structure of the questionnaire (subscales and item allocation). The CFA will assess whether the items load on the expected subscales, whether model fit indices are acceptable, and whether the correlations between factors are plausible. Statistical analysis for the PTSD-iMPACT (3-6 years) validation • Sample and items descriptives: Item description, item means, standard deviations, skewness, kurtosis, and range for caregiver-report. Reliability * Internal consistency: Cronbach's alpha and McDonald's omega for PTSD-iMPACT (caregiver report). * Test-retest reliability: The Intraclass Correlation Coefficient (ICC) will be calculated for PTSD-iMPACT, and the CATS 3-6. Validity Construct Validity: * Convergent validity: Correlations with the PTSD-specific instrument CATS 3-6and the health-related quality of life measure (PedsQL). * Divergent validity: Correlations with questionnaires assessing general emotional and behavioral problems (CBCL subscales: anxiety, depression, oppositional behavior). Criterion Validity: * Concurrent validity: Correlations with the PedsQL. The universal 0-100 rating question will be used as an external criterion. * Predictive validity: Differentiation between individuals with a normal, moderate, elevated and high PTSD symptomatology (Mann-Whitney U test, Cohen's d). ROC analyses will be conducted to determine diagnostic accuracy (sensitivity, specificity). The optimal cut-off value will be determined using the Youden Index. Factorial Validity: • Confirmatory Factor Analysis (CFA): Examination of the theoretically and empirically derived structure of the questionnaire (subscales and item allocation). The CFA will assess whether the items load on the expected subscales, whether model fit indices are acceptable, and whether the correlations between factors are plausible. Handling of missing data Missing data will be addressed using the Multiple Imputation (MI) method in R, which generates multiple plausible datasets by imputing missing values based on observed data. This approach allows for the inclusion of all available data without case-wise deletion, under the assumption that data are missing completely at random (MCAR) or missing at random (MAR). The analyses will be conducted across all imputed datasets, and the results will be pooled to account for the variability introduced by imputation. To assess the potential impact of missing follow-up data, a sensitivity analysis will be performed by comparing results from the pooled imputed datasets with a complete-case analysis, including only participants who completed both measurement points. If substantial differences between these approaches emerge, this may suggest systematic dropout (i.e., data missing not at random \[MNAR\]), which will be considered in the interpretation of the findings. Study Design This study employs a quantitative and confirmatory study design. The confirmatory nature of the study reflects its primary objective - to test predefined hypotheses regarding the psychometric properties of the PTSD-iMPACT measure. Furthermore, the planned project is designed as an international multicenter validation study of the PTSD-iMPACT measure with study sites in Switzerland and Germany. Depending on the individual study site and its available resources, the design is either cross-sectional or longitudinal. The coordinating study center is the Department of Psychosomatics and Psychiatry at the University Children's Hospital Zurich, Switzerland. The coordinating center is responsible for data management and statistical analysis. Recruitment and data collection will be conducted in a clinical and non-clinical sample to increase the generalizability of the findings. The inclusion of both clinical and non-clinical samples is strategically designed to validate the PTSD-iMPACT across a wide range of PTSS severity, functional impairments, and sociodemographic characteristics, thereby strengthening the external validity of the instrument. The Project is structured in three phases: Phase 1 Based on results of a systematic review, qualitative interviews/ focus groups, and expert rating, as well as clinical experience in treating traumatized children and adolescents, an English-language reference version of the PTSD-iMPACT measure was developed. The PTSD-iMPACT measure is available in the following three versions * Self-report by children and adolescents aged between 7 and 18 * Caregiver-report of children and adolescents aged between 7 and 18 * Caregiver-report of children and adolescents aged between 3 and 6 In a first step, two independent forward translations into the respective language (German), a consensus procedure in case of deviations, an independent backward translation into the source language (American English) will be conducted. If necessary, a final round for a consensus procedure in case of deviations from the original version will be created and carried out. Phase 2 The aim of this phase is to collect data and test the psychometric properties in different clinical settings in both Switzerland and Germany and in a non-clinical setting (schools) in Switzerland. Clinical population: Once the minimum number of cases for psychometric analyses has been reached (n≥100 per country and cohort), the data will be analyzed at the coordinating study center to determine the psychometric quality of the new measurement instrument in clinical populations between the ages of 7 and 18 (self- and caregiver-report) and between the ages of 3 and 6 (caregiver-report). In total, each participant (children/adolescents and caregiver) will complete the whole questionnaire battery once and two weeks later a second questionnaire battery, including only PTSD (CATS-2/ CATS 3-6, PTSD-related functional impairment (PTSD-iMPACT), and adjustment disorder (IADQ-CA/IADQ-CA 3-6). If desired, participants may choose to take part in only the first assessment. The effort required is approx. 40 minutes for the first assessment and approx. 15 minutes for the second assessment. Non-clinical setting (Switzerland only): Once the minimum number of cases for psychometric analyses has been reached (n≥100 trauma-exposed children and adolescents, or caregivers of trauma-exposed children and adolescents per type of school (Kindergarten \[only caregivers\], Primarschule \[3rd grade or higher\], Sekundarstufe \[students and caregivers), Gymnasium (students until 18 and their caregivers, and Berufsschule \[until 18 years\]), the data will be analyzed at the coordinating study center to determine the psychometric quality of the new measurement instrument in non-clinical populations between the ages of 7 and 18 (self- and caregiver-report) and between the ages of 3 and 6 (caregiver-report). In total, each participant (children/adolescents and caregivers) will complete the questionnaire battery once. The effort required is approx. 40 minutes. Questionnaire data will be collected using an online secured survey tool, namely REDCap \[20\], hosted by the University Children's Hospital Zurich. Participants will enter all information directly into REDCap or, if schools are unable to provide computers or tablets, via paper-and-pencil questionnaires. Phase 3 Once the data analysis has been completed, the final PTSD-iMPACT measure will be disseminated as a free download in paper-and-pencil format. In addition, a short, easy-to-understand manual with examples of use and evaluation will be developed. The manual will be made available to promote the use of the questionnaire in routine care (outpatient and inpatient). Expected Biases Language distortion: The majority of participants in this study will primarily consist of children, adolescents, and caregivers with a sufficient understanding of the German language. Therefore, the sample will predominantly be comprised of individuals who are fluent in German. Consequently, the overall population of exposed children and adolescents might not be fully represented in the present study. The aforementioned bias will be taken into account when the results are interpreted. Self-selection: There could potentially be a risk that trauma-exposed children and adolescents and caregivers of trauma-exposed children and adolescents who have higher functioning levels both mentally and physically, are more inclined to participate and thus, certain domains of functional impairment and corresponding difficulties will be rated as more or less important. This bias will be considered when discussing the results. Further, a potential bias in the planned study is the distinction between individuals with and without PTEs, which could influence data interpretation. To mitigate this, this classification will only be made after the data collection. Recruitment process Different recruitment procedures will be implemented and conducted for different study sites. Switzerland - clinical institutions As far as possible, every patient and/or caregiver who visits the participating Swiss clinical institutions or medical settings for the first time (inpatient or outpatient) will be invited to participate in the study. The treating mental health specialist will inform the patients and their caregivers verbally about the study. In case of interest, the treating mental health specialist obtains verbal consent to forward their contact information (Name, Surname, phone number, e-mail address) to the study coordinator and give out study information (including consent form). The coordinating research team contacts the potentially participants and provides detailed information about the study (i.e., purpose, duration, timeline, voluntary nature, potential risks, benefits). Signed consent forms are returned electronically by email. After reception, adolescents between 12 and 18 years and caregivers of children/adolescents between 3 and 18 years receive a personalized but de-identified REDCap link via email to complete the initial questionnaire battery. A follow-up link will be sent two weeks later to assess test-retest reliability. For children between 7 and 11 years, the coordinating research team will schedule a phone or video call via Microsoft Teams to assist with completing the initial questionnaire battery, followed by a second call two weeks later to support completion of the follow-up battery. This approach ensures standardization of administration while providing age-appropriate guidance. Patients /caregivers in the study can choose whether their findings is supposed to be reported to their treating mental health specialist. If desired a standardized brief report, entailing the overarching results of the questionnaires, will be send by the study coordinator to the local study leader, respectively, which then distributes the report to the treating mental health specialist at site. Recruitment by the Child Protection Group of the University Children's Hospital Zurich follows the same procedure as described for psychotherapeutic settings, with two exceptions: recruitment is conducted not by a psychotherapist, but by the designated person in charge of the Child Protection Group, and there is no option for questionnaire results to be shared with a treating psychotherapist, as these participants are not recruited within a psychotherapeutic context. Switzerland - medical settings At the University Children's Hospital, medical patients and their caregivers, who were referred to the emergency department and who have signed the hospital's general research consent form will be recruited. Recruitment takes place approximately four weeks after referral. They will be contacted via telephone by trained study personnel of the research team, who provide detailed information about the study (i.e., purpose, duration, timeline, voluntary nature, potential risks, benefits). If they are interested in participating afterwards, they receive study information and informed consent. Signed consent forms are returned electronically by email. After reception, adolescents between 12 and 18 years and caregivers of children/adolescents between 3 and 18 years receive a personalized but de-identified REDCap link to complete the initial questionnaire battery. A follow-up link will be sent two weeks later to assess test-retest reliability. For children between 7 and 11 years, the coordinating research team will schedule a phone or video call via Microsoft Teams to assist with completing the initial questionnaire battery, followed by a second call two weeks later to support completion of the follow-up battery. This approach ensures standardization of administration while providing age-appropriate guidance. Switzerland - Students/ caregiver of kindergartners and students (non-clinical population) Data of students (all German-speaking cantons) and caregivers of kindergartners (all German-speaking cantons) and students (all German-speaking cantons) will be collected. No second assessment two weeks later will take place in the non-clinical population. The survey introduction explicitly states that individuals should not participate if they have already taken part in the study through clinical recruitment, lack sufficient German language skills, or fall outside the eligible age range. The same questionnaires and socio-demographic measures used in the clinical sample will be applied. Participation takes approximately 40 minutes. No follow-up assessment is planned for the non-clinical sample. Kindergartens All kindergartens in the German-speaking part of Switzerland will be invited to participate in the planned study. In case of participation, a REDCap link to the anonymous questionnaires will be send to the caregivers by the teachers via email list, respectively. The start of the survey provides information about the study (purpose, content, handling of data). At the end of the introduction, caregivers have to mark actively if they would like to participate (or not). In case of participation, they subsequently fill out the questionnaire. In case of no participation, the survey ends. Schools Schools in German-speaking cantons will be invited to participate in the planned study. Data collection on site will be coordinated in advance with school leadership and teachers. Whenever possible, data collection will be conducted in the classroom setting, as this provides an optimal environment for participant safety and support. Children and adolescents grade 3 or above will complete the questionnaire battery during class hours. Two weeks before data collection, students/caregivers will receive an information letter about the study. The letter outlines the study's purpose and content and provides advance notice of the upcoming assessment. Further, the letter entails a brief consent form, allowing children and their caregivers to indicate whether the child would like/ is allowed to participate. Adolescents aged 14 and older may sign the form themselves. Completed forms will be returned to the teacher. On the day of data collection, the teacher will verify which students have consented to participate-without disclosing any names to the research team. Students who do not participate, or who have already taken part in the clinical arm of the study, will be given alternative activities during the survey period. On assessment day, three or more trained members of the research team will be present during the assessment, supervising small groups to ensure comprehension and provide assistance if needed. Also, the research team will keep a watching eye on the students to detect any signs of stress or discomfort early on. Participants will complete the questionnaire either digitally (on school-provided tablets or computers) or using a paper-and-pencil format. Members of the research team will each have a copy of the questionnaires. In case of questions, students student can point out the item to the research team, which then uses their copy as a basis to answer the questions. This ensures complete anonymity and confidentiality. Following completion of the questionnaire, the students received an information sheet with a list of easily accessible institutions that provided help for mental health problems. At the start of the session, students will be clearly instructed not to write their names on the questionnaires. In case of a student reaching out to the research team after assessment (e.g., because of emotional distress), no link can be made to their survey data. The study team will not inquire about answers to specific questions. This approach allows for an individualized follow-up without compromising anonymity or data protection. Students will be informed that participation is completely voluntarily and that they can end the assessment at any point (e.g., in case of emotional distress). In case of severe emotional distress, students will be made aware of easily accessible institutions that provided help for mental health problems in children and adolescents. Caregivers of children and adolescent will receive a REDCap link to the questionnaire battery from the teacher by email, and if interested, complete the survey at home. If classroom-based data collection is not feasible for adolescents (aged 12-18), they will be provided with a REDCap survey link to complete the questionnaire independently outside of school hours. The link will be sent by the teacher. All participants will receive contact information for the emergency psychiatric services (KANT) at the Psychiatric University Hospital Zurich, which are available 24/7 in cases of acute psychological distress. Additionally, contact details for the study team will be provided for participants who experience elevated distress and wish to seek support. Germany - clinical institutions or medical settings The German local study site University Clinic for Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Carl von Ossietzky University of Oldenburg, Germany acts subordinate further as co-coordinating center for the following German clinical study sites under Dr. M. Vasileva. Following approval of the Swiss application by the Cantonal Ethics Committee Zurich, the German co-coordinating study site will submit the approval to its respective local ethics committee. Depending on local resources and funding available, the following recruitment/ data collection strategies will be applied at the German study sites: Recruitment Strategy A As far as possible, every patient and/or caregiver who visits the participating clinical institutions or medical settings for the first time (inpatient or outpatient) will be invited to participate in the study. The treating mental health specialist will inform the patients and their caregivers verbally about the study. In case of interest, the treating mental health specialist obtains written consent (equivalent to an Authorization for Release of Psychotherapy Information) that allows the mental health specialist to forward their contact information (Name, Surname, phone number, e-mail address) to the study coordinator M.Sc. A. Vogt via HIN-mail and give out study information (including consent form). The document will be filed in the patient record. The coordinating research contacts the potentially participants and provides detailed information about the study (i.e., purpose, duration, timeline, voluntary nature, potential risks, benefits). Signed consent forms are returned electronically by email. After reception, adolescents between 12 and 18 years and caregivers of children/adolescents between 3 and 18 years receive a personalized but de-identified REDCap link to complete the initial questionnaire battery. A follow-up link will be sent two weeks later to assess test-retest reliability. For children between 7 and 11 years, the coordinating research team will schedule a phone or video call via Microsoft Teams to assist with completing the initial questionnaire battery, followed by a second call two weeks later to support completion of the follow-up battery. This approach ensures standardization of administration while providing age-appropriate guidance. Patients/ caregivers in the study can choose whether their findings is supposed to be reported to their treating mental health specialist. If desired a standardized brief report, entailing the overarching results of the questionnaires, will be send by the Swiss study coordinator A. Vogt to the local study leader, respectively, which then distributes the report to the treating mental health specialist at site. Recruitment Strategy B As far as possible, every patient and/or caregiver who visits the participating clinical institutions or medical settings for the first time (inpatient or outpatient) will be invited to participate in the study. The treating mental health specialist will inform the patients and their caregivers verbally about the study and hand out a flyer about the study, including a generalized link to the questionnaire battery on REDCap. Interested caregivers (of children of all age groups) and adolescents aged 12-18 years will access and complete the questionnaire independently. Children aged 7 to 11 years will not be included in this recruitment strategy. Since the link is general, anonymity is guaranteed. Data can therefore not be shared with the treating psychotherapeutic professional. The respective version of the study information is shown at the start of the questionnaire and participants have to sign the consent form in digital form. Participants will not complete a follow-up questionnaire battery. Recruitment Strategy C As far as possible, every patient and/or caregiver who visits the participating clinical institutions or medical settings for the first time (inpatient or outpatient) will be invited to participate in the study trough the local study site leaders and their research team. Informed consent will be obtained and data will be collected through the Swiss REDCap server and tool from the University-Children's Hospital Zurich via tablet at the German study site. Data collection will be anonymously. Informed consent will be collected through the local study site leader or a member of their research team electronically via REDCap before administering the questionnaires. No procedure relating to the project will be carried out before consent has been given by the participant. Only data collected after consent is given will be used for analysis. Any contact details shared with the study team will be deleted if the potential participants decide not to take part in the study.

This study is open to adults with chronic kidney disease at risk of progression. People with and without type 2 diabetes can take part in this study. The study is open to people who take other medicines called angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). People who already take empagliflozin or any other sodium-glucose cotransporter-2 inhibitor (SGLT2i) can also join. The study is also open to people who currently do not take any of these treatments. The purpose of this study is to find out whether a medicine called BI 690517 helps people with chronic kidney disease when taken in combination with a study medicine called empagliflozin. Worsening of kidney function increases the risk for kidney failure, cardiovascular disease, and heart disease. This study has 2 parts. In the first part, participants get empagliflozin or placebo matching BI 690517 for at least 6 weeks. Participants continue taking ACEi or ARB throughout the study if such treatments are indicated. In the second part, participants are divided into 2 groups by chance. One group takes BI 690517 tablets and the other group takes placebo tablets. Placebo tablets look like BI 690517 tablets but do not contain any medicine. Participants take 1 tablet once a day in addition to empagliflozin for the duration of the study. The doctors document when participants experience worsening of their kidney disease, go to hospital due to heart failure, or die of cardiovascular problems during the study. The time to these events is compared between the 2 treatment groups to see whether the treatment works. The study continues until the required number of events have occurred which is about 3 to 4 years. During this time, participants visit the study site about 4 times within the first 6 months. Then they visit the study site every 6 months. At the visits, doctors regularly check participants' health, take blood and urine samples, measure blood pressure and weight, check kidney function, and take note of any unwanted effects.