Periodic Reporting for period 1 - HT-ADVANCE (Improving treatment efficacy in hypertension by biomarker-guided personalised decision support)
Reporting period: 2023-03-01 to 2024-08-31
HT-ADVANCE aims to improve the personalized treatment of high blood pressure (hypertension) by using special biological markers (MOMICS) to help doctors choose the right treatment for each patient. Hypertension is a major global health risk factor, but despite several treatment options, blood pressure remains elevated in more than half of the patients. This is often because secondary forms due to an underlying and curable disease, such as endocrine hypertension (EHT), aren’t identified and treated properly. Also, different patients respond differently to the same drugs, leading to inefficient treatments being delivered.
The goal of HT-ADVANCE is to test two types of MOMICS biomarkers to:
1. Identify patients with EHT.
2. Predict how patients with primary hypertension will respond to treatment.
We believe use of MOMICS biomarkers will improve diagnosis of secondary forms of hypertension and indicate the treatment of choice for each patient. To prove this, we will conduct three clinical trials and use Artificial Intelligence to analyze genetic and metabolic data. We will also evaluate the cost-effectiveness of using these biomarkers, produce ethical and legal guidelines for the use of Artificial intelligence in the clinical setting, and create a plan to implement them in clinical practice.
The project will be carried out by several excellence hypertension centers and will build on previous successful research. We hope HT-ADVANCE will lead to more personalized, efficient, and cost-effective treatments for hypertension, for improved cure and prevention of cardiovascular and metabolic complications.
The goal of HT-ADVANCE is to test two types of MOMICS biomarkers to:
1. Identify patients with EHT.
2. Predict how patients with primary hypertension will respond to treatment.
We believe use of MOMICS biomarkers will improve diagnosis of secondary forms of hypertension and indicate the treatment of choice for each patient. To prove this, we will conduct three clinical trials and use Artificial Intelligence to analyze genetic and metabolic data. We will also evaluate the cost-effectiveness of using these biomarkers, produce ethical and legal guidelines for the use of Artificial intelligence in the clinical setting, and create a plan to implement them in clinical practice.
The project will be carried out by several excellence hypertension centers and will build on previous successful research. We hope HT-ADVANCE will lead to more personalized, efficient, and cost-effective treatments for hypertension, for improved cure and prevention of cardiovascular and metabolic complications.
In period one the main activities were to prepare and start the HT-PREDICT trial and set up the necessary virtual infrastructure for the data management and machine learning models, as well as to put in place all necessary procedures for the biological sample analysis of the three different trials in the project.
For HT-PREDICT (a randomised controlled trial on predictive value of MOMICS biomarkers for treatment response and adverse effects of antihypertensive therapy), we have obtained medical ethical approval for the site in Nijmegen and started recruiting subjects during period 1. First subjects were completing the study by the end of period 1. At the time of writing, the site in Zürich was still waiting for the final step of approval by Swissmedic, whereas approval by local ethics had already been granted. For HT-ENDO (a randomised controlled trial on the diagnostic value of MOMICS biomarkers for endocrine hypertension), the design and methodology have been finalised in collaboration with all the consortium partners. The methodological and statistical work for those two clinical trials had started in parallel.
A Multi-Omics Data Management Platform (MODMAP) has been developed and is up and running for tracking patient samples in the already started HT-PREDICT trial but also for the other two upcoming trials. In cooperation with the omics centers it has been tested before going live to ensure that the movement of samples from the clinical collecting centres to the OMICS centers and the subsequent reporting of results to the database is fully operational. MODMAP also integrates a clinician interface for visualisation of clinical predictions from the ML pipeline, providing an end-to-end solution allowing data flow from/to clinical studies An electronic case report form (eCRF) for the HT-PREDICT trial has been developed and is currently being used for running the trial.
The partners conducting the omics analysis have set up new protocols and equipment and trained the staff members for the future samples from the clinical trials to be analysed. All groups have reviewed their standard operating procedures, the measurement reproducibility, normalisation and quality control processes to ensure their OMICS measurements methods are robust; all equipment is fully operational.
A summary and inventory of the relevant literature and legal and ethical documentation for the project, including the recently published EU Artificial Intelligence-Act, was set up for the project and a first webinar on ethical aspects of the use of Artificial Intelligence in clinical research has been organised for the consortium members.
For the future economic analysis the HT-ENDO trial protocol was reviewed in order to ensure that the necessary parameters will be taken into account in the design of the clinical trial.
The scientific work was framed by the project management, which set in place the governance of the project, organised the meetings and took care of financial and legal issues of the grant. In terms of dissemination the project website was set up and a LinkedIn page created with frequents posts on the life of the project.
For HT-PREDICT (a randomised controlled trial on predictive value of MOMICS biomarkers for treatment response and adverse effects of antihypertensive therapy), we have obtained medical ethical approval for the site in Nijmegen and started recruiting subjects during period 1. First subjects were completing the study by the end of period 1. At the time of writing, the site in Zürich was still waiting for the final step of approval by Swissmedic, whereas approval by local ethics had already been granted. For HT-ENDO (a randomised controlled trial on the diagnostic value of MOMICS biomarkers for endocrine hypertension), the design and methodology have been finalised in collaboration with all the consortium partners. The methodological and statistical work for those two clinical trials had started in parallel.
A Multi-Omics Data Management Platform (MODMAP) has been developed and is up and running for tracking patient samples in the already started HT-PREDICT trial but also for the other two upcoming trials. In cooperation with the omics centers it has been tested before going live to ensure that the movement of samples from the clinical collecting centres to the OMICS centers and the subsequent reporting of results to the database is fully operational. MODMAP also integrates a clinician interface for visualisation of clinical predictions from the ML pipeline, providing an end-to-end solution allowing data flow from/to clinical studies An electronic case report form (eCRF) for the HT-PREDICT trial has been developed and is currently being used for running the trial.
The partners conducting the omics analysis have set up new protocols and equipment and trained the staff members for the future samples from the clinical trials to be analysed. All groups have reviewed their standard operating procedures, the measurement reproducibility, normalisation and quality control processes to ensure their OMICS measurements methods are robust; all equipment is fully operational.
A summary and inventory of the relevant literature and legal and ethical documentation for the project, including the recently published EU Artificial Intelligence-Act, was set up for the project and a first webinar on ethical aspects of the use of Artificial Intelligence in clinical research has been organised for the consortium members.
For the future economic analysis the HT-ENDO trial protocol was reviewed in order to ensure that the necessary parameters will be taken into account in the design of the clinical trial.
The scientific work was framed by the project management, which set in place the governance of the project, organised the meetings and took care of financial and legal issues of the grant. In terms of dissemination the project website was set up and a LinkedIn page created with frequents posts on the life of the project.