A multicentre, multi-national, double-blind, randomised, active-controlled, parallel-group clinical study to assess the safety and efficacy of PDA10 (Epoetin-alpha) vs. Eprex® in patients with anaemia of chronic renal failure.

BACKGROUND: Erythropoietin stimulating agent (ESA) has been standard of care in treating renal anaemia for the past 20 years. Many patients have limited access to ESA in view of long-term costs leading to suboptimal ESA dosage. Biosimilar epoetin is a potential cost-effective alternative to originator for optimal renal anaemia management. OBJECTIVE: To determine efficacy and safety of PDA10 in treating renal anaemia in haemodialysis patients, in comparison to the originator epoetin-α, Eprex®. METHODS: A phase 3, multicentre, multi-national, double-blind, randomised, active-controlled and parallel group study conducted over 40 weeks in Malaysia and Korea. End stage kidney disease patients undergoing regular haemodialysis who were on erythropoietin treatment were recruited. The study has 3 phases, which included a 12-week titration phase, followed by 28-week double-blind treatment phase and 24-week open-label extension phase. RESULTS: The PDA10 and Eprex® were shown to be therapeutically equivalent (p < 0.0001) with mean absolute change in haemoglobin from baseline of - 0.176 (± 0.91) g/dl and - 0.118 (± 1.114) g/dl, respectively. Weekly dose change was 10.01 IU/kg/week in PDA10 group and 10.30 IU/kg/week in Eprex® group, which has no significant difference. There were no significant differences in the safety profile between PDA10 and Eprex® groups. CONCLUSION: This study has confirmed the therapeutic equivalence between PDA10 and Eprex® in terms of efficacy, dosage requirement and safety profile in haemodialysis patients with renal anaemia. TRIAL REGISTRATION: The study was registered with the National Medical Research Register ( NMRR-13-400-16313 ). This study has been registered retrospectively with Clinical Research Information Service ( CRiS ), Republic of Korea on 25 March 2021.

Muscle Status Response to Oral Nutritional Supplementation in Hemodialysis Patients With Protein Energy Wasting: A Multi-Center Randomized, Open Label-Controlled Trial.

Background: Muscle wasting, observed in patients with end-stage kidney disease and protein energy wasting (PEW), is associated with increased mortality for those on hemodialysis (HD). Oral nutritional supplementation (ONS) and nutrition counseling (NC) are treatment options for PEW but research targeting muscle status, as an outcome metric, is limited. Aim: We compared the effects of combined treatment (ONS + NC) vs. NC alone on muscle status and nutritional parameters in HD patients with PEW. Methods: This multi-center randomized, open label-controlled trial, registered under ClinicalTrials.gov (Identifier no. NCT04789031), recruited 56 HD patients identified with PEW using the International Society of Renal Nutrition and Metabolism criteria. Patients were randomly allocated to intervention (ONS + NC, n = 29) and control (NC, n = 27) groups. The ONS + NC received commercial renal-specific ONS providing 475 kcal and 21.7 g of protein daily for 6 months. Both groups also received standard NC during the study period. Differences in quadriceps muscle status assessed using ultrasound (US) imaging, arm muscle area and circumference, bio-impedance spectroscopy (BIS), and handgrip strength (HGS) methods were analyzed using the generalized linear model for repeated measures. Results: Muscle indices as per US metrics indicated significance (p < 0.001) for group × time interaction only in the ONS + NC group, with increases by 8.3 and 7.7% for quadriceps muscle thickness and 4.5% for cross-sectional area (all p < 0.05). This effect was not observed for arm muscle area and circumference, BIS metrics and HGS in both the groups. ONS + NC compared to NC demonstrated increased dry weight (p = 0.039), mid-thigh girth (p = 0.004), serum prealbumin (p = 0.005), normalized protein catabolic rate (p = 0.025), and dietary intakes (p < 0.001), along with lower malnutrition-inflammation score (MIS) (p = 0.041). At the end of the study, lesser patients in the ONS + NC group were diagnosed with PEW (24.1%, p = 0.008) as they had achieved dietary adequacy with ONS provision. Conclusion: Combination of ONS with NC was effective in treating PEW and contributed to a gain in the muscle status as assessed by the US, suggesting that the treatment for PEW requires nutritional optimization via ONS.

The state of nutrition care in outpatient hemodialysis settings in Malaysia: a nationwide survey.

BACKGROUND: This study aimed to assess the situational capacity for nutrition care delivery in the outpatient hemodialysis (HD) setting in Malaysia by evaluating dietitian accessibility, nutrition practices and patients' outcomes. METHODS: A 17-item questionnaire was developed to assess nutrition practices and administered to dialysis managers of 150 HD centers, identified through the National Renal Registry. Nutritional outcomes of 4362 patients enabled crosscutting comparisons as per dietitian accessibility and center sector. RESULTS: Dedicated dietitian (18%) and visiting/shared dietitian (14.7%) service availability was limited, with greatest accessibility at government centers (82.4%) > non-governmental organization (NGO) centers (26.7%) > private centers (15.1%). Nutritional monitoring varied across HD centers as per albumin (100%) > normalized protein catabolic rate (32.7%) > body mass index (BMI, 30.7%) > dietary intake (6.0%). Both sector and dietitian accessibility was not associated with achieving albumin ≥40 g/L. However, NGO centers were 36% more likely (p = 0.030) to achieve pre-dialysis serum creatinine ≥884 µmol/L compared to government centers, whilst centers with dedicated dietitian service were 29% less likely (p = 0.017) to achieve pre-dialysis serum creatinine ≥884 µmol/L. In terms of BMI, private centers were 32% more likely (p = 0.022) to achieve BMI ≥ 25.0 kg/m2 compared to government centers. Private centers were 62% less likely (p <  0.001) while NGO centers were 56% less likely (p <  0.001) to achieve serum phosphorus control compared to government centers. Patients from centers with a shared/visiting dietitian had 35% lower probability (p <  0.001) to achieve serum phosphorus levels below 1.78 mmol/L compared to centers without access to a dietitian. CONCLUSIONS: There were clear discrepancies in nutritional care in Malaysian HD centers. Changes in stakeholder policy are required to ensure that dietitian service is available in Malaysian HD centers.