A total of 26 adults provided informed consent and were evaluated for entry into the study; 23 patients were enrolled and received at least one hemodialysis treatment with the Optiflux dialyzer. Per protocol, 4 patients were withdrawn from the study prior to the completion of the Optiflux period as a result of missing a hemodialysis treatment with the Optiflux dialyzer. These 4 patients were aged 62 to 79 years and included 2 men and 2 women. Three of the patients had diabetes as the primary cause of ESKD and one had ESKD secondary to hypertension/large-vessel disease. Of the 19 patients who completed the Optiflux period, one patient (a 28-year-old female with ESKD secondary to glomerulonephritis) missed her first treatment on the dialyzer with Endexo (visit 13) and was withdrawn from the trial. The safety population consisted of the 18 patients who received at least one hemodialysis session with the dialyzer with Endexo. As a result of missing multiple treatments with the dialyzer with Endexo secondary to a localized foot infection (not judged to be device-related), one participant was withdrawn from the study per protocol. As such, 17 patients completed a minimum of 36 hemodialysis treatments on the dialyzer with Endexo and made up the analysis population.
Baseline Characteristics And Hemodialysis Treatment Delivered
The median age of patients in the safety population (N = 18) was 63.5 years (range 27–87 years). The population was mostly female (78%) and identified as white (67%). Diabetes was the most common cause of ESKD, accounting for 61% of cases; hypertension/large-vessel disease, cystic/hereditary/congenital diseases and glomerulonephritis accounted for 22%, 11% and 6% of cases, respectively.
Initial hemodialysis prescriptions had blood flow rates that ranged from 300 mL/min to 500 mL/min and dialysate flow rates of 450 mL/min to 800 mL/min. In the Optiflux period, 23 patients received a total of 268 hemodialysis treatments, and 18 participants received 664 hemodialysis treatments in the Endexo period. In the analysis population, delivered hemodialysis treatment parameters were comparable across treatment periods (Table 1).
Table 1
Delivered hemodialysis for the analysis population (N = 17 completers)
Measure | Optiflux | Endexo |
Blood pump flow rate, mL/min | 447.5 (32.3) | 447.7 (37.8) |
Dialysate flow rate, mL/min | 698.0 (60.7) | 698.5 (62.9) |
Treatment time, min | 205.2 (19.1) | 207.5 (20.5) |
Blood volume processed, L | 82.6 (8.1) | 82.8 (10.7) |
Ultrafiltration volume, mL | 2156.9 (632.6) | 2187.1 (739.0) |
Data presented as mean (SD) |
Primary And Secondary Endpoints
In the Endexo period, the mean (SD) Kuf of the dialyzer with Endexo at visit 13 was 15.85 (10.33) mL/h/mmHg (primary endpoint). This in vivo value was derived from a mean (SD) UFR of 652.35 (232.34) mL/h and mean TMP of 46.25 (15.44) mmHg observed at 15 minutes (± 5 min) after the recorded start of hemodialysis at visit 13 in the analysis population. At the same session, mean (SD) dialysis adequacy (i.e., spKt/V) was 1.98 (0.56) and URR was 79.59% (12.15).
Using data across the entirety of each treatment period, the mean (SD) spKt/V for the Optiflux dialyzer and dialyzer with Endexo were 1.94 (0.3) and 2.09 (0.41), respectively. Treatment with the dialyzers was associated with comparable mean (SD) URRs in the Optiflux (80.81% [4.33]) and Endexo (81.87% [5.91]) periods.
Mean (SD) concentrations of β2M before hemodialysis were similar at visit 1 (Optiflux) and visit 13 (Endexo): 32.29 (8.37) µg/mL and 32.9 (6.55) µg/mL, respectively. Hemodialysis treatment with the dialyzer with Endexo resulted in corrected mean (SD) β2M removal rates that were numerically 47% higher than those observed with the Optiflux dialyzer: 67.73% (16.32). Mean (SD) pre-dialysis serum albumin levels were comparable for all visits and both dialyzers, ranging from 3.91 (0.21) g/dL (visit 22; Endexo) to 3.97 (0.34) g/dL (visit 1; Optiflux). Albumin levels before dialysis generally remained constant across the Endexo period (mean [SD] of 3.95 [0.21], 3.91 [0.21], 3.94 [0.25] and 3.91 [0.31] g/dL at visits 13, 22, 34 and 46, respectively). Treatment with both dialyzers resulted in similar increases in serum albumin levels (Fig. 2).
During the 4-week Optiflux period, 4 out of 23 patients reported a total of 7 AEs. This equates to a rate of 2.6 AEs per 100 hemodialysis sessions. No single AE was reported by more than one patient during the Optiflux period, and none of the events were considered device-related. During the Endexo period, 11 patients reported a total of 32 AEs, for a rate of 4.8 AEs per 100 hemodialysis sessions. The most commonly reported AEs (those occurring in ≥ 2 patients) in the Endexo period were headache, reported by 3 patients (16.7%; 0.5 events per 100 hemodialysis sessions), and lethargy, hypotension, vomiting and extremity pain, each reported by 2 patients (11.1%; 0.3 events per 100 hemodialysis sessions). None of the AEs experienced in the Endexo period were considered device-related. Three serious AEs were reported during the study (gastrointestinal hemorrhage, localized infection and hypertensive emergency) and all occurred during the Endexo period. None of the serious AEs were considered device- or procedure-related. Throughout the trial, there were no AEs that led to study discontinuation and no deaths.
Additional Endpoints
The impact of dialysis on hematologic parameters (i.e., hemoglobin, hematocrit and red blood cell count) was evaluated before and after the first study use of the dialyzer with Endexo. There was an absence of clinically significant changes in these parameters. Patients exhibited a mean (SD) hemoglobin increase of 0.49 (0.93) g/dL after the first use of the dialyzer with Endexo. A mean (SD) platelet count decrease of 6.47 (13.94) x 103/µL equating to a 2.7% (5.70) reduction (from a pre-dialysis mean [SD] of 198.94 [55.85] x 103/µL) was observed after use of the dialyzer with Endexo.
Protocol-driven modifications for hemodialysis treatment-related medications were excluded, so investigators were permitted to alter medications based on clinical judgment and institutional guidelines. Relative to observations during the Optiflux period, the mean dose of heparin was reduced by 11.2% during the Endexo period (mean [SD]: 4507 [3349] IU vs 3760 [2471] IU). In a post hoc analysis that excluded 18 hemodialysis sessions from 6 patients with extremely high (i.e., ≥ 10,000 IU) and extremely low (i.e., 0 IU) recorded heparin doses, the dialyzer with Endexo was associated with a 3.7% mean reduction in heparin doses. Relative to treatment during the Optiflux period, patients received lower doses of ESA (12.0% mean reduction) and higher doses of intravenous iron sucrose (13.4% mean increase) during the Endexo period. In contrast, the mean administered doses of calcitriol, doxercalciferol and saline were comparable across treatment periods (i.e., varied < 10%).
Complement activation was assessed at the first visit during each treatment period, with measurements taken before hemodialysis and 30 minutes after the treatment began. There was no evidence of overt complement activation, as C5a and C3a levels remained largely unchanged. A slight increase in sC5b-9 was observed for both dialyzers, with mean increases from 260 ng/mL to 323 ng/mL during the Optiflux period and 224 ng/mL to 304 ng/mL during the Endexo period.
Thrombus scoring was performed at the end of dialyzer use for every treatment session. Scoring was identified as grade 1 (good clear dialyzer, no detectable clotting), 2 (overall light redness, minimal clot formation), 3 (overall moderate redness, clot formation but hemodialysis was still possible) or 4 (total clotting of the dialyzer necessitating a stop in treatment or replacement of the dialyzer). The mean (SD) thrombus scores in the Optiflux and Endexo periods were 1.14 (0.4) and 1.29 (0.52), respectively. A single grade 4 thrombus score was recorded during the study, and it occurred during the Optiflux period.