Second Clinical Evaluation of THERANOVA-500 Dialyzer in Chronic Hemodialysis (HD)

Study Overview
=================
Brief Summary
-----------------
Single blinded randomized controlled trial comparing Expanded Hemodialysis (HDx) using THERANOVA-500 dialyzer versus conventional hemodialysis (HD) using REVACLEAR-400 dialyzer in chronic hemodialysis patients over a 6-week intervention period. Primary endpoint is post-hemodialysis recovery time. Secondary endpoints are six pre-dialysis biomarker levels (b2-microglobuline, procalcitonine, free light chains (gamma-lambda), IL-6, CRP) and three Quality of Life (QoL)(adapted KDQoL-SF questionnaire, EQ-5D, and rESAS).

Detailed Description
-----------------
This is a randomized controlled trial involving 70 subjects divided in 4 groups: 25 single blinded subjects using THERANOVA-500 dialyzer enabling Expanded Hemodialysis (HDx) ; 25 single blinded subjects using REVACLEAR-400 dialyzer enabling conventional hemodialysis (HD); 10 non-blinded subjects using THERANOVA-500 enabling Expanded Hemodialysis (HDx) and 10 non-blinded subjects using REVACLEAR-400 dialyzer enabling conventional hemodialysis (HD) for their chronic hemodialysis treatments over an active intervention period of 6 weeks. All subjects are to be dialyzed using REVACLEAR-400 enabling conventional hemodialysis (HD) for two weeks prior and for two weeks after the intervention period. Primary endpoint is mean post-hemodialysis recovery time (as reported by subjects once weekly) between groups (THERANOVA-500 vs REVACLEAR-400) (all subjects) during the 6-week intervention period. Secondary endpoints are: Post-hemodialysis recovery time change (mean of 2-week pre and 2-week post intervention period compared to mean during 6-week intervention period)(mean THERANOVA-500 vs mean REVACLEAR-400)(all subjects), Post-hemodialysis recovery time difference (mean between blinded and non-blinded THERANOVA-500 treated subjects during the 6-week intervention period, Post-hemodialysis recovery time difference (mean between blinded and non-blinded REVACLEAR-400 treated subjects during the 6-week intervention period), Post-hemodialysis recovery time difference mean gap between secondary endpoints 2 and 3, Percentage of subjects who report no (zero) recovery time (mean THERANOVA-500 vs mean REVACLEAR-400) during 6-week intervention period (all subjects), Pre and post 6-week intervention period pre-dialysis difference levels of beta-2 microglobulin (mean THERANOVA-500 vs mean REVACLEAR-400)(all subjects)(in nmol/L), Pre and post 6-week intervention period pre-dialysis difference levels of procalcitonin (mean THERANOVA-500 vs mean REVACLEAR-400)(all subjects)(in ng/ml), Pre and post 6-week intervention period pre-dialysis difference levels of free light chains (gamma and lambda)(mean THERANOVA-500 vs mean REVACLEAR-400)(all subjects)(in mg/L), Pre and post 6-week intervention period pre-dialysis difference levels of interleukine-6 (mean THERANOVA-500 vs mean REVACLEAR-400)(all subjects)(in pg/ml), Pre and post 6-week intervention period pre-dialysis difference levels of C reactive protein (CRP)(mean THERANOVA-500 vs mean REVACLEAR-400)(all subjects)(in mg/L), Quality of life change (pre and at 2 weeks of intervention period) (mean THERANOVA-500 vs mean REVACLEAR-400)(all subjects)(assessed by adapted KDQoL-SF questionnaire)(max score 130), Quality of life change (pre and at 4 weeks of intervention period) (mean THERANOVA-500 vs mean REVACLEAR-400)(all subjects) assessed by adapted KDQoL-SF questionnaire)(max score 130), Quality of life change (at 4 weeks of intervention period and week 8 of study)(mean THERANOVA-500 vs mean REVACLEAR-400)(all subjects) assessed by adapted KDQoL-SF (max score 130), Quality of life change (pre and at 2 weeks of intervention period)(mean THERANOVA-500 vs mean REVACLEAR-400)(all subjects)(assessed by EQ-5D questionnaire)(max score 125), Quality of life change (pre and at 4 weeks of intervention period)(mean THERANOVA-500 vs mean REVACLEAR-400)(all subjects)(assessed by EQ-5D questionnaire)(max score 125), Quality of life change (at 4 weeks of intervention period and week 8 of study)(mean THERANOVA-500 vs mean REVACLEAR-400)(all subjects)(assessed by EQ-5D questionnaire (max score 125), Quality of life change (pre and at 2 weeks of intervention period (mean THERANOVA-500 vs mean REVACLEAR-400)(all subjects)(assessed by rESAS)(max score 100), Quality of life change (pre and at 4 weeks of intervention period (mean THERANOVA-500 vs mean REVACLEAR-400)(all subjects)(assessed by rESAS)(max score 100), Quality of life change (at 4 weeks of intervention period and week 8 of study)(mean THERANOVA-500 vs mean REVACLEAR-400)(all subjects)(assessed by rESAS)(max score 100), Subjects's QoL questionnaire fill preference (adapted KD QoL-SF vs EQ-5D vs rESAS) at study week 8.

Official Title
-----------------
Second Clinical Evaluation of THERANOVA-500 Dialyzer in Chronic Hemodialysis (HD)

Conditions
-----------------
End Stage Renal Disease on Dialysis

Intervention / Treatment
-----------------
* Device: THERANOVA-500 dialyzer
* Device: REVACLEAR-400 dialyzer


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age greater than 18 years, all genders. HD at DrGLDUHC for more than 3 months, 3 times/week schedule, and using REVACLEAR-400. Good vascular access (blood flow (Qb) > 300 during entire previous 6 HD sessions, no per-HD alteplase treatments used over the last 2 weeks, routine alteplase-lock allowed) Signed informed consent Likely to be able to participate for the duration of the clinical evaluation (no trips, no elective procedures, no transfer to another dialysis modality or HD facility, etc). Able to fill questionnaires, staff assistance allowed. Exclusion Criteria: HD more than 3 times/week HD on other dialyzers than REVACLEAR-400 Poor vascular access (from staff and Nephrologists' evaluation) No consent or unable to answer questionnaires even with staff assistance.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1 blinded group on THERANOVA-500 dialyzer (Expanded Hemodialysis (HDx)) 1 blinded group on REVACLEAR-400 dialyzer (conventional hemodialysis (HD)) 1 non-blinded group on THERANOVA-500 dialyzer (Expanded Hemodialysis (HDx)) 1 non-blinded group on REVACLEAR-400 dialyzer (conventional hemodialysis (HD))
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blinded THERANOVA-500 dialyzer<br>This group of 25 subjects is dialyzed with masked THERANOVA-500 dialyzer enabling Expanded Hemodialysis (HDx) therapy. | Device: THERANOVA-500 dialyzer<br>* THERANOVA-500 dialyzer is a hemofilter that enables Expanded Hemodialysis (HDx) therapy.<br>|
| Placebo Comparator: Blinded REVACLEAR-400 dialyzer<br>This group of 25 subjects is dialyzed with masked REVACLEAR-400 dialyzer enabling conventional hemodialysis (HD). | Device: REVACLEAR-400 dialyzer<br>* REVACLEAR-400 dialyzer is an usual hemofilter that enables conventional hemodialysis (HD).<br>|
| Experimental: Unblinded THERANOVA-500 dialyzer<br>This group of 10 subjects is dialyzed with unmasked THERANOVA-500 dialyzer which enables Expanded Hemodialysis (HDx) therapy. | Device: THERANOVA-500 dialyzer<br>* THERANOVA-500 dialyzer is a hemofilter that enables Expanded Hemodialysis (HDx) therapy.<br>|
| Placebo Comparator: Unblinded REVACLEAR-400 dialyzer<br>This group of 10 subjects is dialyzed with unmasked REVACLEAR-400 dialyzer which enables conventional hemodialysis (HD). | Device: REVACLEAR-400 dialyzer<br>* REVACLEAR-400 dialyzer is an usual hemofilter that enables conventional hemodialysis (HD).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-dialysis recovery time (intervention period) | All subjects are asked weekly on their mid-week session how long did it take them to recover from their previous hemodialysis session for the entire duration of the project (10 weeks). Mean post-dialysis recovery time report (in hours) of all subjects on THERANOVA-500 (5 reports/subject) compared to mean of all subjects on REVACLEAR-400 reports during the 6-week intervention period (5 reports/subject) is the primary outcome measure.(intended statistical test: 2-sample t-Test)(re continuous data, n=35/group) | through 6-week intervention period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-hemodialysis recovery time change (THERANOVA-500 vs REVACLEAR-400) | This outcome refers to the mean post-hemodialysis recovery time reports (in hours) during 6-week intervention period (5 reports/subject) minus mean post-hemodialysis recovery time reports of 2-week pre and 2-week post intervention period (5 reports/subject)(all subjects)(intended statistical test: paired t-Test)(re continuous data, n=35/group) | through 10-week study | 
| Post-hemodialysis recovery time difference (THERANOVA-500) | This outcome refers to the mean difference between blinded and non-blinded THERANOVA-500 treated subjects of post-hemodialysis recovery time (in hours) during the 6-week intervention period (5 reports/subject)(intended statistical test: Wilcoxon Rank Sum Test)(re continuous data, n <= 25/group). This outcome is to assess extent of placebo effect. | through 6-week intervention period | 
| Post-hemodialysis recovery time difference (REVACLEAR-400) | This outcome refers to the mean difference between blinded and non-blinded REVACLEAR-400 treated subjects of post-hemodialysis recovery time (in hours) during the 6-week intervention period (5 reports/subject)(intended statistical test: Wilcoxon Rank Sum Test)(re continuous data, n <= 25/group). This outcome is to assess extent of placebo effect. | through 6-week intervention period | 
| Post-hemodialysis recovery time difference mean gap (THERANOVA-500 vs REVACLEAR-400) | This outcome refers to comparison between mean difference of secondary outcome 3 and mean of secondary outcome 4 of post-hemodialysis recovery time (in hours)(intented statistical test: 2-sample t-Test)(re mean of means). This outcome is to assess extent of differential placebo effects between the intervention groups. | through 6-week intervention period | 
| Percentage of subjects who report no (zero) recovery time (THERANOVA-500 vs REVACLEAR-400) | This outcome refers to the mean difference of percentage of subjects reporting no (zero) recovery time after treatment with THERANOVA-500 compared to mean percentage of subjects reporting no (zero) recovery time after treatment with REVACLEAR-400 during the 6-week intervention period (all subjects)(intended statistical test: 2-sample t-TEST (re continuous data, n = 35/group) | through 6-week intervention period | 
| Pre and post 6-week intervention period pre-dialysis levels of beta-2 microglobulin | This outcome refers to the mean difference between pre-dialysis levels of beta-2 microglobulin (in nmol/L) (assay: immunoturbidimetry) pre-intervention period compared to post 6-week intervention period between all subjects treated with THERANOVA-500 and all subjects treated with REVACLEAR-400 (intended statistical test: paired t-Test (re continuous data, n = 35/group) | 6 weeks | 
| Pre and post 6-week intervention period pre-dialysis levels of procalcitonin | This outcome refers to the mean difference between pre-dialysis levels of procalcitonin (in ng/ml) (assay: ELFA (Enzyme-Linked Fluorescent Assay) pre-intervention period compared to post 6-week intervention period between all subjects treated with THERANOVA-500 and all subjects treated with REVACLEAR-400 (intended statistical test: paired t-Test (re continuous data, n = 35/group) | 6 weeks | 
| Pre and post 6-week intervention period pre-dialysis levels of free light chains | This outcome refers to the mean difference between pre-dialysis levels of free light chains (gamma and lambda) (in mg/L) (assay: immunoturbidimetry) pre-intervention period compared to post 6-week intervention period between all subjects treated with THERANOVA-500 and all subjects treated with REVACLEAR-400 (intended statistical test: paired t-Test (re continuous data, n = 35/group) | 6 weeks | 
| Pre and post 6-week intervention period pre-dialysis levels of interleukine-6 | This outcome refers to the mean difference between pre-dialysis levels of interleukine-6 (in pg/ml) (assay: ELISA) pre-intervention period compared to post 6-week intervention period between all subjects treated with THERANOVA-500 and all subjects treated with REVACLEAR-400 (intended statistical test: paired t-Test (re continuous data, n = 35/group) | 6 weeks | 
| Pre and post 6-week intervention period pre-dialysis levels of C reactive protein | This outcome refers to the mean difference between pre-dialysis levels of C reactive protein (in mg/L) (assay: Heterogeneous enzyme immunoassay) pre-intervention period compared to post 6-week intervention period between all subjects treated with THERANOVA-500 and all subjects treated with REVACLEAR-400 (intended statistical test: paired t-Test (re continuous data, n = 35/group) | 6 weeks | 
| Quality of life (QoL) change (pre and at 2 weeks of intervention period)(adapted KDQoL-SF) | This outcome refers to the mean difference between QoL assessed by adapted KDQoL-SF questionnaire (max score 130, higher better) pre-intervention period compared to post 2-week intervention period between all subjects treated with THERANOVA-500 and all subjects treated with REVACLEAR-400 (intended statistical test: paired t-Test (re continuous data, n = 35/group). This questionnaire is a locally validated adapted version of KDQoL-SF, Version 1.3, Copyright, RAND 1995,1996,1997, available in English and French. | 2 weeks | 
| Quality of life (QoL) change (pre and at 4 weeks of intervention period)(adapted KDQoL-SF) | This outcome refers to the mean difference between QoL assessed by adapted KDQoL-SF questionnaire (max score 130, higher better) pre-intervention period compared to post 4-week intervention period between all subjects treated with THERANOVA-500 and all subjects treated with REVACLEAR-400 (intended statistical test: paired t-Test (re continuous data, n = 35/group). This questionnaire is a locally validated adapted version of KDQoL-SF, Version 1.3, Copyright, RAND 1995,1996,1997, available in English and French. | 4 weeks | 
| Quality of life (QoL) change (at 4 weeks of intervention period and week 8 of study)(adapted KDQoL-SF) | This outcome refers to the mean difference between QoL assessed by adapted KDQoL-SF questionnaire (max score 130, higher better) at 4-week intervention period and week 8 of study between all subjects treated with THERANOVA-500 and all subjects treated with REVACLEAR-400 (intended statistical test: paired t-Test (re continuous data, n = 35/group). This questionnaire is a locally validated adapted version of KDQoL-SF, Version 1.3, Copyright, RAND 1995,1996,1997, available in English and French. | 4 weeks | 
| Quality of life (QoL) change (pre and at 2 weeks of intervention period)(EQ-5D) | This outcome refers to the mean difference between QoL assessed by EQ-5D questionnaire (max score 125, higher better) pre-intervention period compared to post 2-week intervention period between all subjects treated with THERANOVA-500 and all subjects treated with REVACLEAR-400 (intended statistical test: paired t-Test (re continuous data, n = 35/group). This questionnaire is a common validated instrument by EuroQol group available in multiple languages used here in its English and French Canadian versions. | 2 weeks | 
| Quality of life (QoL) change (pre and at 4 weeks of intervention period)(EQ-5D) | This outcome refers to the mean difference between QoL assessed by EQ-5D questionnaire (max score 125, higher better) pre-intervention period compared to post 4-week intervention period between all subjects treated with THERANOVA-500 and all subjects treated with REVACLEAR-400 (intended statistical test: paired t-Test (re continuous data, n = 35/group). This questionnaire is a common validated instrument by EuroQol group available in multiple languages used here in its English and French Canadian versions. | 4 weeks | 
| Quality of life (QoL) change (at 4 weeks of intervention period and week 8 of study)(EQ-5D) | This outcome refers to the mean difference between QoL assessed by EQ-5D questionnaire (max score 125, higher better) at 4-week intervention period and week 8 of study between all subjects treated with THERANOVA-500 and all subjects treated with REVACLEAR-400 (intended statistical test: paired t-Test (re continuous data, n = 35/group). This questionnaire is a common validated instrument by EuroQol group available in multiple languages used here in its English and French Canadian versions. | 4 weeks | 
| Quality of life (QoL) change (pre and at 2 weeks of intervention period)(rESAS) | This outcome refers to the mean difference between QoL assessed by rESAS questionnaire (max score 100, higher better) pre-intervention period compared to post 2-week intervention period between all subjects treated with THERANOVA-500 and all subjects treated with REVACLEAR-400 (intended statistical test: paired t-Test (re continuous data, n = 35/group). This questionnaire is the revised Edmonton Symptom Assessment System instrument available in English and in French. | 2 weeks | 
| Quality of life (QoL) change (pre and at 4 weeks of intervention period)(rESAS) | This outcome refers to the mean difference between QoL assessed by rESAS questionnaire (max score 100, higher better) pre-intervention period compared to post 4-week intervention period between all subjects treated with THERANOVA-500 and all subjects treated with REVACLEAR-400 (intended statistical test: paired t-Test (re continuous data, n = 35/group). This questionnaire is the revised Edmonton Symptom Assessment System instrument available in English and in French. | 4 weeks | 
| Quality of life (QoL) change (at 4 weeks of intervention period and week 8 of study)(rESAS) | This outcome refers to the mean difference between QoL assessed by rESAS questionnaire (max score 100, higher better) at 4-week intervention period and week 8 of study between all subjects treated with THERANOVA-500 and all subjects treated with REVACLEAR-400 (intended statistical test: paired t-Test (re continuous data, n = 35/group). This questionnaire is the revised Edmonton Symptom Assessment System instrument available in English and in French. | 4 weeks | 
| Subjects's QoL questionnaire fill preference | At the end of the study (week 10) all subjects will be asked which QoL questionnaire (between the adapted KDQoL-SF, EQ-5D and rESAS) they prefer to fill for future routine use in the hemodialysis unit. | at week 10 of study |