High-Volume HDF, reduced mortality & patient-reported outcomes
Study Design and Methods
Aim: To investigate whether high-dose HDF offers survival benefits as compared with conventional high-flux HD.
Patients: 1360 patients from 61 dialysis centers in eight European countries, treated with high-flux HD, and deemed to be candidates for a convection volume of at least 23 L per session.
Design: A pragmatic, 1:1 randomized controlled trial with outcomes assessed over 30 months (median). 683 patients were assigned to online high-volume HDF and 677 patients to high-flux HD. High-volume HDF means post-dilution HDF with online production of fluids and convection volume ≥ 23 L per session.
Method: Convection volume targets achieved with stepwise adjustment over 2-3 weeks; interventions and outcomes assessed over 30 months (median)
Primary outcome: Death from any cause.
Secondary outcome: Key secondary outcomes were cause-specific mortality, composite of fatal and nonfatal cardiovascular events, kidney transplantation, and recurrent hospitalizations for any cause and for causes related to infection
Results
Primary outcome:
Death from any cause occurred in 118 patients (17.3%) in the HDF group and in 148 patients (21.9%) in the HD group. Patients in the HDF group had a 23% lower rate of mortality (hazard ratio (HR), 0.77; 95% confidence interval (CI), 0.65- 0.93; P = 0.005).
Secondary outcome:
- The risk of death from cardiovascular causes and the composite outcome of fatal or nonfatal cardiovascular outcomes were similar in the HDF and the HD group; with a reduction of infection-related death in favor of high-dose HDF, including from Covid-19 (HR, 0.69; 95% CI, 0.49 to 0.96).
- The Kt/V value over the course of the trial was higher in the HDF group than in the HD group (1.74 vs. 1.65).
- The target convection volume of at least 23 L was achieved in 92% of delivered HDF sessions, with a stable mean convection volume of 25.2 L over the course of the trial.
Conclusions
The CONVINCE study found a lower risk of death from any cause in patients receiving high-volume HDF than among patients receiving high-flux HD. Infection-related and cardiovascular deaths showed a suggestion of benefit for HDF. The study differs from previous studies in that it enrolled patients who were likely candidates for high-dose HDF nearly all the time. It did not identify an association between failure to achieve the high-dose target and any particular patient characteristic or vascular access type. The trial results support the evidence that high-volume HDF can result in a clinically important survival benefit.
Study Design and Methods
The CONVINCE trial demonstrated a survival benefit for patients receiving high-volume hemodiafiltration (HVHDF) compared with high-flux hemodialysis (HD).
A secondary objective in this randomized controlled trial (RCT) was to evaluate the impact on health-related quality of life (HRQoL).
- A patient-reported outcome (PRO) is any health report provided directly by the patient.
- HRQoL is one of the most important patient-reported outcomes.
- The patient’s perceptions of how renal replacement therapies impact physical and psychological well-being are important.
To assess HRQoL, electronic patient-reported outcome measures from the Patient-Reported Outcome Measurement Information System (PROMIS) were used.
- These comprise the three fundamental health domains as defined by the World Health Organization:
- Physical Health (physical function, fatigue, pain interference, sleep disturbance),
- Mental Health (depression, anxiety, cognitive function), and
- Social Health (social participation).
- PROs from 1,291 patients were collected at baseline and every 3 months until completion of the study or treatment.
The mean change from baseline after 30 months between HVHDF and HD were assessed for all HRQoL domains.
A linear-mixed model was used to assess HRQoL change from baseline through follow-up time points.
To account for the mortality difference demonstrated in CONVINCE, a post-hoc joint model was conducted to investigate the robustness of the linear-mixed model. The joint model considers the potential dependency of self-reported health status measures and observed differences on mortality rates, thereby reducing the potential bias in the linear-mixed model.
Results
Throughout the study, there was a small-to-modest deterioration in all HRQoL domains for both groups, with a slower worsening for all HRQoL domains in the HVHDF group.
After 30 months, the overall HRQoL (including all domains) was significantly better for the HVHDF group than the HD group (p = 0.006).
Cognitive function in the HVHDF group declined at half the rate of the HD group (linear-mixed and joint model).
Based on the joint model, the HVHDF group reported significantly slower deterioration in physical function, cognitive function, pain interference, and the ability to participate in social activities compared to the HD group.
Strengths & Limitations
The CONVINCE trial provided a comprehensive and robust evaluation of HRQoL by conducting more frequent and detailed assessments of patient-reported health data than any previous RCTs.
It is the largest nephrology trial that involved patients in developing the questionnaire and using novel electronic PRO measures.
There is no established threshold for PROMIS measures that has been determined to be clinically meaningful to patients with kidney replacement therapy.
The investigated population had an overall lower risk of death than reported in other studies, potentially limiting generalizability of the results.
Conclusions
CONVINCE participants reported a slow but constant decline in all HRQoL parameters.
For all domains, HVHDF sustained HRQoL more effectively than HD; this was most pronounced for cognitive function.
Similar to the observed survival benefits in CONVINCE, consistent delivery of HVHDF provides continued beneficial effects on HRQoL over time.
CONVINCE PRO
Significant results (joint model)
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2 Blankestijn PJ et al., CONVINCE Scientific Committee Investigators, Effect of Hemodiafiltration or Hemodialysis on Mortality in Kidney Failure, N Engl J Med 2023 Aug 24;389(8):700-709