Periodic Reporting for period 3 - CONVINCE (The Comparison of High-Dose Heamodiafiltration (HDF) versus Haemodialyse)
Okres sprawozdawczy: 2021-01-01 do 2022-06-30
Context
End stage kidney disease (ESKD) is a serious medical condition with high mortality rates and hence with an unmet clinical need. Globally, approximately 10% of the general population suffers from a form of kidney injury of which a proportion will progress to ESKD. The survival probability at one, two and five years is around 81, 68 and 37%, respectively. Therefore, there is an unmet and urgent medical need to improve ESKD patient survival and to address Health Related Quality of Life (HRQL).
Currently there are three types of dialysis treatments: Haemodialysis (HD), peritoneal dialysis (PD) and haemodiafiltration (HDF). HD is currently the treatment of choice in 80% of ESKD patients across Europe, in absence of any current alternatives applicable for the majority of ESKD patients. CONVINCE will not focus on PD as an alternative to HD, as only a minority of patients are treated by PD in Europe, with many patients transferring to haemodialysis with time. Therefore, CONVINCE focuses on a comparison between high-dose HDF and HD, with the hypothesis that high-dose HDF will be the superior treatment and hence can become first treatment of choice in ESKD patients.
The concept of HDF is relatively simple. In HD the basic transport mechanism for removal of waste products is diffusion. HDF combines diffusion with another transport mechanism: convection. Convection is the removal of waste products diluted in an ultrafiltrate which is produced by a pressure difference over the membrane, and is replaced by “clean” replacement fluids. Extensive pre-clinical research has shown that by combining these two mechanisms, as in high-dose HDF, accumulating waste products in the body due to the failing kidneys are more effectively removed from the body. In this respect, dose, i.e. total ultrafiltered volume expressed as L/session, seems to be of crucial significance. High-dose HDF may reduce mortality in ESKD patients.
To achieve a change in clinical practice, we run a large clinical study proving HDF (cost) effectiveness compared to HD. If proven true, a substantial reduction in mortality may be achievable for 80% of the ESKD patients currently managed with HD. At the end of the study the Guideline and review bodies will be updated with the new evidence obtained.
Objectives
Haemodifiltration (HDF): Setting the novel standard treatment for ESKD patients. CONVINCE will pursue the following objectives:
1) To prove the superiority of high-dose HDF as compared to conventional guideline based HD (i.e. current standard of care) in terms of morbidity, mortality and HRQL;
2) To collect data to conduct a comprehensive economic evaluation of HDF compared to support Health Technology Assessment (HTA) considerations among Member States and healthcare to facilitate patients acceptance and uptake of high-dose HDF across Europe;
3) To develop and implement Patient Reported Outcome Measures (PROMs) and Patient Reported Experience Measures (PREMS) to capture patient satisfaction;
4) To develop best practises and new guidelines on the most effective and efficient dialysis strategy;
5) To share results in close collaboration with all stakeholders and end-users, and to establish a sound evidence- and regulatory basis for the implementation of high-dose HDF across Europe.
References
1) Brück K, Stel V, Gambaro G,et al . J Am Soc Nephrol. 2016 Jul;27(7):2135-47.
End stage kidney disease (ESKD) is a serious medical condition with high mortality rates and hence with an unmet clinical need. Globally, approximately 10% of the general population suffers from a form of kidney injury of which a proportion will progress to ESKD. The survival probability at one, two and five years is around 81, 68 and 37%, respectively. Therefore, there is an unmet and urgent medical need to improve ESKD patient survival and to address Health Related Quality of Life (HRQL).
Currently there are three types of dialysis treatments: Haemodialysis (HD), peritoneal dialysis (PD) and haemodiafiltration (HDF). HD is currently the treatment of choice in 80% of ESKD patients across Europe, in absence of any current alternatives applicable for the majority of ESKD patients. CONVINCE will not focus on PD as an alternative to HD, as only a minority of patients are treated by PD in Europe, with many patients transferring to haemodialysis with time. Therefore, CONVINCE focuses on a comparison between high-dose HDF and HD, with the hypothesis that high-dose HDF will be the superior treatment and hence can become first treatment of choice in ESKD patients.
The concept of HDF is relatively simple. In HD the basic transport mechanism for removal of waste products is diffusion. HDF combines diffusion with another transport mechanism: convection. Convection is the removal of waste products diluted in an ultrafiltrate which is produced by a pressure difference over the membrane, and is replaced by “clean” replacement fluids. Extensive pre-clinical research has shown that by combining these two mechanisms, as in high-dose HDF, accumulating waste products in the body due to the failing kidneys are more effectively removed from the body. In this respect, dose, i.e. total ultrafiltered volume expressed as L/session, seems to be of crucial significance. High-dose HDF may reduce mortality in ESKD patients.
To achieve a change in clinical practice, we run a large clinical study proving HDF (cost) effectiveness compared to HD. If proven true, a substantial reduction in mortality may be achievable for 80% of the ESKD patients currently managed with HD. At the end of the study the Guideline and review bodies will be updated with the new evidence obtained.
Objectives
Haemodifiltration (HDF): Setting the novel standard treatment for ESKD patients. CONVINCE will pursue the following objectives:
1) To prove the superiority of high-dose HDF as compared to conventional guideline based HD (i.e. current standard of care) in terms of morbidity, mortality and HRQL;
2) To collect data to conduct a comprehensive economic evaluation of HDF compared to support Health Technology Assessment (HTA) considerations among Member States and healthcare to facilitate patients acceptance and uptake of high-dose HDF across Europe;
3) To develop and implement Patient Reported Outcome Measures (PROMs) and Patient Reported Experience Measures (PREMS) to capture patient satisfaction;
4) To develop best practises and new guidelines on the most effective and efficient dialysis strategy;
5) To share results in close collaboration with all stakeholders and end-users, and to establish a sound evidence- and regulatory basis for the implementation of high-dose HDF across Europe.
References
1) Brück K, Stel V, Gambaro G,et al . J Am Soc Nephrol. 2016 Jul;27(7):2135-47.
Work performed and main results
It can be concluded that the consortium has faced some challenges in relation to the start-up of the trial. Matters like the implementation of GDPR, but also the processing time of the ethical submissions to the local ethical committees took more time than originally planned. Although working in parallel, not all countries have been started up yet, the consortium plans to expand the recruitment period.
The first patients have been randomized, the trial management and data collection work well. The first results show that sites are performing well, even demonstrating the possibilities of bulk inclusion.
The set-up for data collection and data management have been well set-up. Progress with data analysis has been satisfactory. Actual analysis took some time, caused by the overall delay in the start-up and recruitment speed in the clinical trial.
The PREMS-PROMS questionnaires are giving feedback on patient perspective and closely monitored.
A newsletter for site staff has been issued to shared best practices amongst the participating sites. The project has been presented on several conferences and lectures, to spread awareness of this end of discussion study. In addition, a website has been aired, to inform the wider public.
It can be concluded that the consortium has faced some challenges in relation to the start-up of the trial. Matters like the implementation of GDPR, but also the processing time of the ethical submissions to the local ethical committees took more time than originally planned. Although working in parallel, not all countries have been started up yet, the consortium plans to expand the recruitment period.
The first patients have been randomized, the trial management and data collection work well. The first results show that sites are performing well, even demonstrating the possibilities of bulk inclusion.
The set-up for data collection and data management have been well set-up. Progress with data analysis has been satisfactory. Actual analysis took some time, caused by the overall delay in the start-up and recruitment speed in the clinical trial.
The PREMS-PROMS questionnaires are giving feedback on patient perspective and closely monitored.
A newsletter for site staff has been issued to shared best practices amongst the participating sites. The project has been presented on several conferences and lectures, to spread awareness of this end of discussion study. In addition, a website has been aired, to inform the wider public.
Progress beyond the state of art
If our hypothesis is proven correct, this will mean a major breakthrough for several reasons. It will show that a meaningful advancement in the care of ESKD patients is possible and achievable in every day clinical care almost without changing existing infrastructure, including facilities, equipment and staff. Most importantly, high-dose HDF is anticipated to be not only safe and highly cost-effective, but also should reduce patient mortality by 20-30%. In other words, this study will show that true innovation can not only be achieved by a totally new idea, but also by using presently available knowledge and by mobilizing clinical and industrial key players to implement and develop this technology. Regarding patient perspectives, the consortium will make use of novel PREMS-PROMS analyses techniques.
Expected results and impacts
Taken together CONVINCE can be considered a low-risk high gain project. When successful, CONVINCE is likely to immediately and drastically improve treatment and mortality outcomes of 80% of patients, which is to the best of our knowledge unequalled in any other complex disease. Also, when the trial shows that there is no differences in clinical outcome and/or HRQL variables, then the discussion on the possible role of HDF is definitely closed.
CONVINCE will conduct a comprehensive, robust and well standardized RCT to prove the superiority of high-dose HDF and implement it as standard clinical care for ESKD patients across Europe and beyond.
Furthermore, the consortium will interact with all relevant end-user groups across Europe and beyond, including patients, regulatory bodies and the research community. This ensures that all expertise, resources and infrastructures are bundled to allow maximum impact
If our hypothesis is proven correct, this will mean a major breakthrough for several reasons. It will show that a meaningful advancement in the care of ESKD patients is possible and achievable in every day clinical care almost without changing existing infrastructure, including facilities, equipment and staff. Most importantly, high-dose HDF is anticipated to be not only safe and highly cost-effective, but also should reduce patient mortality by 20-30%. In other words, this study will show that true innovation can not only be achieved by a totally new idea, but also by using presently available knowledge and by mobilizing clinical and industrial key players to implement and develop this technology. Regarding patient perspectives, the consortium will make use of novel PREMS-PROMS analyses techniques.
Expected results and impacts
Taken together CONVINCE can be considered a low-risk high gain project. When successful, CONVINCE is likely to immediately and drastically improve treatment and mortality outcomes of 80% of patients, which is to the best of our knowledge unequalled in any other complex disease. Also, when the trial shows that there is no differences in clinical outcome and/or HRQL variables, then the discussion on the possible role of HDF is definitely closed.
CONVINCE will conduct a comprehensive, robust and well standardized RCT to prove the superiority of high-dose HDF and implement it as standard clinical care for ESKD patients across Europe and beyond.
Furthermore, the consortium will interact with all relevant end-user groups across Europe and beyond, including patients, regulatory bodies and the research community. This ensures that all expertise, resources and infrastructures are bundled to allow maximum impact