Implementation

WP1: Network set-up and legal/ethics regulation

Work Package 1 focuses on ensuring full regulatory, ethical, and operational readiness for the SGLT2 HYPE clinical trial. Led by UKSH and supported by all recruiting partners, this work includes identifying and aligning with local regulatory frameworks, finalising participant insurance coverage, obtaining ethical and regulatory approvals (via CTIS and national bodies), and registering the trial in relevant international databases. Additionally, the importation of investigational medicinal products will comply with German legislation. To ensure high-quality and consistent trial execution, standard operating procedures (SOPs) will be implemented and supported by partner training across all clinical sites. Together, these tasks establish a strong foundation for a compliant, efficient, and ethically sound trial launch.

Objectives:

• To obtain necessary approvals from national regulatory authorities and allow initiation of the trial across all sites
• To implement SOPs for all network partners, focusing on trial protocols and data collection methods to ensure consistency and high-quality data across all sites

WP2: Set-up and initiation of the clinical trial database

Work Package 2 ensures that the SGLT2 HYPE trial is supported by a strong digital and data foundation. This includes creating easy-to-use electronic forms (eCRF) for collecting patient information, setting up a secure online system for randomising participants, and developing tools to assess the potential cost-effectiveness of the treatment. A central database will be built to safely store and manage all trial data, following high standards for data quality and accessibility. Additionally, a secure system will be put in place to transfer heart ultrasound (echocardiography) images for expert analysis. These steps help ensure the trial runs smoothly, efficiently, and with the highest level of data integrity.

Objectives:

• To develop and initiate an efficient clinical trial database system
• To implement a reliable randomisation process that ensures patients are appropriately assigned to treatment groups in a manner that supports the trial’s scientific integrity
• To develop a design for a cost-effectiveness analysis (CEA), that can be applied and adapted to different EU countries, reflecting different conditions regarding health care systems and costs
• To set up the infrastructure for DICOM transfer from study sites to the echocardiography core lab

WP3: Enabling direct patient involvement using eHealth

Work Package 3, lead by MUI, focuses on developing a patient-centred mobile app to support home blood pressure monitoring (HBPM) and collect quality-of-life data (QoL). The app will be interactive and user-friendly, allowing participants to record their blood pressure at home and regularly complete questionnaires, with real-time data sharing and reminders. Developed in close cooperation with patients and healthcare professionals, it will ensure high usability, data security, and regulatory compliance. In parallel, a secure digital health innovation platform (DHIP) will be established to integrate the app and all related components into one functional system. This platform will support efficient data processing and storage while adhering to the highest standards for data interoperability, privacy, and accessibility.

 

Objectives:

• To develop an interactive app to enable HBPM and regular queries of QoL questionnaires, facilitating the exchange of information in real time;
• To develop and operate a comprehensive digital health innovation platform (DHIP) that integrates all individual components and third-party elements into a functional overall system

WP4: Set-up and initiation of the biobank

Work Package 4 ensures high-quality and standardised handling of biological samples collected during the SGLT2 HYPE trial. Led by INSERM, this work includes creating detailed procedures (SOPs) for the collection, processing, storage, and shipping of samples to guarantee consistency and quality across all sites. These guidelines will be aligned with ethical and legal standards and shared throughout the project. In addition, trial sites will receive training and sampling kits to support correct implementation. INSERM will oversee training, monitor sample quality, and update procedures as needed to ensure compliance and best practice in biobanking throughout the trial.

 

Objective

• Initiate decentral biobanking procedures for the efficient handling, storage, and management of blood samples collected during the trial

 

WP5: Design and set-up of the statistical analysis

Work Package 5 provides the statistical foundation for the SGLT2 HYPE trial, ensuring scientific rigor in its design and analysis. Led by IHF in collaboration with UKSH, INSERM, and U.PORTO, this work includes drafting the study protocol’s statistical sections, developing the detailed Statistical Analysis Plan (SAP), and creating the randomisation strategy to assign participants fairly to treatment groups. The team will also develop secure data handling procedures and tools using SAS software to prepare and analyse the trial data. These efforts ensure robust, transparent, and regulatory-compliant results for evaluating the effectiveness of the SGLT2 inhibitor in managing hypertension.

 

Objectives:

• To ensure scientific integrity of the statistical analyses
• To guarantee the random assignment of patients to the study arms

WP6  (WP15, WP20, WP25, WP30): Management of Patient Enrolment, Treatment and Visits

Work Package 6 coordinates the safe and efficient delivery of the study treatment and monitors patient participation throughout the SGLT2 HYPE trial. After import, the investigational treatment is distributed to clinical sites across the European Union and Ukraine, along with standardized blood pressure measurement devices. Patients are enrolled and receive regular support and safety checks, including follow-up visits every 6-months. These visits track health outcomes, treatment effects, and quality of life over several years. A small group of participants will also receive echocardiography exams to better understand how the treatment may benefit heart function. This work ensures that patients are supported and that high-quality data is collected across all trial sites, contributing to a reliable evaluation of the treatment’s long-term impact.

Objectives:

• To initiate patient enrolment at the clinical sites by ensuring they have the necessary resources to begin patient enrolment
• To ensure a reliable Investigational Medicina Product’s (IMPs)-distribution strategy for study participants
• To systematically conduct and manage regular visits during treatment period after safety visit, collecting consistent data across all trial sites
• To assess the cardiac function and structure in a subset of participants through analysis of echocardiographic data

WP7 (WP16, WP21, WP26, WP31): Monitoring and Data Management

Work Package 7 ensures the safety of participants and the integrity of data throughout the SGLT2 HYPE clinical trial. Led by UKSH, the team will establish a robust safety monitoring system, including reporting and managing any side effects or adverse events, in line with EU and Ukrainian regulations. A risk-based monitoring strategy will focus efforts where they are needed most, helping trial sites stay compliant and efficient. A secure data management system will be put in place to collect and store trial data from various sources, including digital tools, health questionnaires, and imaging results. Data will be regularly checked for quality and accuracy, and site staff will receive training to quickly resolve any issues. This work also supports open science by ensuring that research data and findings are made accessible to the scientific community, while maintaining privacy and data protection standards.

Objectives:

• To initiate a monitoring system for protocol adherence and participant safety during treatment period, promptly addressing any adverse events or protocol deviations
• To initiate the respective study sites after securing the necessary regulatory, personnel and logistical requirements and conduct regular trial monitoring
• To ensure the project data are in accordance with FAIR principles
• To operate the server infrastructure and software for the clinical trial database system and the data infrastructure for Digital Imaging and Communications in Medicine (DICOM) transfer from study sites to the echocardiography core
• To maintain high data quality and integrity of the clinical trial database with rigorous data monitoring, validation processes and query management

 

WP8: Statistical Analysis

Work Package 8 focuses on analysing the trial data to ensure meaningful and scientifically sound results. Led by IHF, the team will update the statistical analysis plan whenever changes are made to the trial protocol. Two planned safety analyses will be carried out during the study—first at the halfway point of patient recruitment and then after recruitment is complete—to monitor for any potential risks. At the end of the trial, the data will be carefully analysed to determine whether the treatment is effective in reducing major cardiovascular events. These results will be used to prepare a scientific publication for a high-impact medical journal. In addition, summary data will be shared with other teams in the project to support health economics and biomarker studies, and results will be made publicly available in clinical trial registries.

Objectives:

• To keep the statistical concepts up to date to maintain scientific integrity
• To ensure the safety of the study participants during the project
• To answer the central study question of whether patients benefit from the SGLT2i treatment regarding the defined endpoints
• To obtain scientific statements on the health economic significance of clinical results and the role of biomarkers

 

 

 

WP9: Cost effectiveness and health-economic analysis

Work Package 9 evaluates whether the new treatment is cost-effective compared to standard care. Using a theoretical model, the team will first estimate the potential value of adding an SGLT2 inhibitor to existing hypertension treatment based on published research. Once the clinical trial is complete, real patient data will be added to the model to analyse how well the treatment works in relation to its cost. The main outcome will show how much it costs to gain one healthy year of life through the new treatment. This analysis will be carried out for at least two European countries, using their specific healthcare costs, to help decision-makers assess whether the treatment offers good value for money.

Objectives

• To provide data on the economic impact of MACE reductions due to SGLT2i treatment

 

 

 

WP10: Sub-cohort analyses: Sex specific as well as socio-demographic analysis

Work Package 10 explores how different patient characteristics may influence the effectiveness of the treatment with dapagliflozin. The team will conduct detailed analyses to see whether treatment outcomes differ between men and women, and whether factors like age, body weight, kidney function, income, education, or living environment impact how well patients respond. By dividing the participants into subgroups, researchers will assess if the treatment works better for certain populations and identify any factors that might influence its success. These insights help ensure that future treatment recommendations can be more tailored to individual patient needs.

Objectives:

• To statistically examine sex-depended effects of SGLT2i treatment in patients with high blood pressure
• To get insights into the statistical impact of sociodemographic factors on efficacy of SGLT2i treatment on primary and secondary endpoints and on patient adherence
• To statistically examine whether pre-defined subgroups (according to the statistical analysis plan) have an influence on the effects of SGLT2i treatment in hypertensive patients

 

WP11: Mechanistic Studies of SGLT2-inhibitors in Hypertension by Biomarker Analysis

 Work Package 11 focuses on understanding how the SGLT2-inhibitor (SGLT2i) treatment works at the biological level and exploring ways to personalize treatment in the future. A central biobank will be set up in Nancy, France, to process and store high-quality blood samples collected from study participants across Europe. These samples will be analyzed to identify proteins (biomarkers) linked to cardiovascular health, using advanced technologies to explore how the treatment affects the heart and blood vessels. Researchers will also examine changes in specific biomarkers known to be involved in heart disease and use computer-based network analyses to map how these biological signals interact. Finally, using the collected data, the team will develop predictive models to estimate how individual patients might respond to the treatment—paving the way for more personalized and effective care for people with hypertension.

Objectives:

• To conduct precise biomarker measurements using state-of-the-art techniques
• To gain critical insights into SGLT2i’s mechanisms related to cardio-vascular health in hypertension by bioinformatic analysis
• To identify predictive biomarker pattern in hypertension, enhancing precision of hypertension treatment strategies

 

WP12  (WP17, WP22, WP27, WP32): Stakeholder engagement & Exploitation

Work Package 12 ensures that the SGLT2 HYPE trial remains relevant, inclusive, and impactful by actively involving key stakeholders throughout the project. From the beginning, medical experts, patient organisations, professional societies, and health policy representatives are consulted to shape and refine the study design. Their feedback is regularly gathered and used to improve how the trial is conducted. Toward the end of the project, the results will be shared with experts to inform updates to hypertension treatment guidelines and support evidence-based health policy decisions thus ensuring the uptake an use of the project`s exploitable results by end-users beyond the project lifetime. A dedicated strategy will also guide how the study’s most important results are used after the project ends, ensuring long-term benefits. Additionally, a tailored recruitment strategy—developed with input from patients and trial sites—aims to reach a diverse group of participants, making the study as representative and inclusive as possible.

Objectives:

• To integrate and leverage in a co-creation process the knowledge and expertise of health care professional societies, Health Technology Assessment (HTA) bodies, and patient organisations into the study design and execution for ensuring the study’s relevance to clinical guidelines, daily practice, and health policy from the beginning
• To establish a dynamic feedback loop with healthcare professional societies, HTA bodies, and patient organisations throughout the trial to refine study protocols and ensure the continuous alignment of the research with clinical, patient, and policy needs
• To plan and promote the use and exploitation of the project results, by involving HTA bodies and professional societies, aiming to translate the findings into meaningful improvements in clinical guidelines for hypertension and sustainable health policy measures
• To develop a sufficient patient recruitment strategy in co-creation process with patient organisations

WP13 (WP18, WP23, WP28, WP33): Dissemination & Communication

Work Package 13 will run in parallel with the other packages during the entire lifecycle of the project and focuses on dissemination and communication of the project’s aims, objectives and results. Its key aim is the widest possible dissemination of the project’s results to both the research community and all other interested/identified stakeholders.

In line with the European Commission’s efforts to foster collaboration and knowledge exchange, WP13 will actively engage with other EU-funded projects under the same topic, as encouraged by the Health and Digital Executive Agency (HaDEA). By establishing strong links within this broader research community, WP13f aims to promote synergies, amplify impact, and contribute to advancing innovation across Europe.

Objectives:

• Achieve sustainable impact for the SGLT2-HYPE project results and innovations by:
• Planning and coordinating all dissemination and communication activities of the project to relevant key stakeholder
• groups (public, scientific community, policymakers etc.)
• Facilitating knowledge transfer by the provision of trainings, information materials, focused videos
• Support the planning and promotion of the use and exploitation of the project results

WP14  (WP19, WP24, WP29, WP34): Project Management

WP14 will provide an effective project management programme and governance structure to ensure that SGLT2 HYPE’s objectives are successfully fulfilled within the lifetime of the project. WP14 will facilitate collaboration between the consortium’s partners whilst ensuring all EC requirements are respected.

Objectives:

• Set-up an effective communication infrastructure, foster integration process within the consortium
• Ensure the proper overall management, coordination and controlling of the project
• Identify possible risks, set-up mitigation measures, contingency plans and define measurable indicators for project progress
• Ensure proper ethical conduct of the clinical trial according to ICH-GCP criteria at all study sites
• Ensure the project data are in accordance with FAIR principles

WP35: Ethics Requirements

This work package sets out the ‘ethics requirements’ that the project must comply with.

 

Objectives:

• Ensure compliance with the ‘ethics requirements’