Benefits and harms of high-dose haemodiafiltration versus high-flux haemodialysis: the comparison of high-dose haemodiafiltration with high-flux haemodialysis (CONVINCE) trial protocol

Abstract

IntroductionEnd-stage kidney disease (ESKD) is a major public health problem affecting more than 2 million people worldwide. It is one of the most severe chronic non-communicable diseases. Haemodialysis (HD) is the most common therapeutic option but is also associated with a risk of cardiovascular events, hospitalisation and suboptimal quality of life. Over the past decades, haemodiafiltration (HDF) has become available. Although high-dose HDF has shown some promising survival advantage compared to conventional HD, the evidence remains controversial. A Cochrane systematic review found, in low-quality trials, with various convective forms of dialysis, a reduction in cardiovascular, but not all-cause mortality and the effects on non-fatal cardiovascular events and hospitalisation were uncertain. In contrast, an individual patient data analysis suggested that high-dose HDF reduced both all-cause and cardiovascular mortality compared to HD. In view of these discrepant results, a definitive trial is required to determine whether high-dose HDF is preferable to high-flux HD. The comparison of high-dose HDF with high-flux HD (CONVINCE) study will assess the benefits and harms of high-dose HDF versus a conventional high-flux HD in adults with ESKD.Methods and analysisThis international, prospective, open label, randomised controlled trial aims to recruit 1800 ESKD adults treated with HD in nine European countries. Patients will be randomised 1:1 to high-dose HDF versus continuation of conventional high-flux HD. The primary outcome will be all-cause mortality at 3 years’ follow-up. Secondary outcomes will include cause-specific mortality, cardiovascular events, all-cause and infection-related hospitalisations, patient-reported outcomes (eg, health-related quality of life) and cost-effectiveness.Ethics and disseminationThe CONVINCE study will address the question of benefits and harms of high-dose HDF compared to high-flux HD for kidney replacement therapy in patients with ESKD with a focus on survival, patient perspectives and cost-effectiveness.Trial registration numberNetherlands National Trial Register (NTR 7138).

Trends in Adaptive Design Methods in Dialysis Clinical Trials: A Systematic Review

“…Group sequential designs were the most common type of adaptive design method used; 35 (61.4%) trials (22 [71%] in dialysis populations and 13 [50%] in dialysis outcome trials; Table 1 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ). The O’Brien-Fleming stopping boundary was the most common stopping rule, used in 9 trials (25.7%), followed by Lan DeMets, used in 8 trials (22.9%).…”

Association between implementation of novel therapies and improved survival in patients starting haemodialysis: the Swedish Renal Registry 2006–15

“…We recognize that there is still a debate regarding the effectiveness of some treatments. For instance, although several reports have indicated that HDF with a high exchange volume is superior to conventional HD, the evidence is still controversial [ 4 , 25 ], and trials are on-going [ 26 ]. Furthermore, not all trials have seen better outcomes with more frequent dialysis [ 14 ], but at least one trial [ 27 ] and various observational studies [ 6 , 28 ] support that more frequent dialysis regimes may have a positive effect on complications and survival.…”

Improving Clearance for Renal Replacement Therapy

“…16,17 A randomized trial is now being conducted to more rigorously test the benefit of high volume ultrafiltration. 18 Efforts to further increase the clearance of middle molecules are also ongoing. Some efforts have been made to increase the clearance of ß 2 microglobulin and other low molecular weight proteins by passing blood over sorbent columns.…”