METHOD: A multicentre, parallel, randomised, controlled, open-label, non-inferiority trial was conducted. Adult patients receiving CAPD were randomised in a 1:1 ratio to SSL or STS. The primary outcome was the rate of peritonitis after 1 year of follow-up.

RESULTS: A total of 472 subjects were randomised (SSL, n = 233; STS, n = 239). One subject in each group was excluded from the analysis as they withdrew consent before the first dialysis dose. Four hundred and seventy subjects (SSL, n = 232; STS, n = 238) were included in the modified intention-to-treat analysis. Non-inferiority between two groups was established as no significant difference was found in peritonitis rate (incident rate ratio: 0.91, 95% CI: 0.65-1.28). No significant difference was detected in weekly Kt/V (p = 0.58) and creatinine clearance (p = 0.55). However, the average ultrafiltration volume was significantly lower in SSL, with a mean difference of 93 ml (p < 0.01). SSL also demonstrated a 2.57-times higher risk of device defect than STS (95% CI: 1.77-3.75).

Objective: To evaluate the efficacy of oral mixed tocotrienols for patients with diabetic peripheral neuropathy.

Design, Setting, and Participants: The Vitamin E in Neuroprotection Study (VENUS) was a parallel, double-blind, placebo-controlled trial that recruited participants from January 30, 2011, to December 7, 2014, with 12 months of follow-up. This trial screened 14 289 patients with diabetes from 6 health clinics and ambulatory care units from 5 public hospitals in Malaysia. A total of 391 patients who reported neuropathic symptoms were further assessed with Total Symptom Score (TSS) and Neuropathy Impairment Score (NIS). Patients 20 years or older with a TSS of 3 or higher and an NIS of 2 or higher were recruited.

Interventions: Patients were randomized to receive 200 mg of mixed tocotrienols twice daily or matching placebo for 12 months. Patients with hyperhomocysteinemia (homocysteine level ≥2.03 mg/L) received oral folic acid, 5 mg once daily, and methylcobalamin, 500 μg thrice daily, in both groups.

Main Outcomes and Measures: The primary outcome was patient-reported neuropathy TSS (lancinating pain, burning pain, paresthesia, and asleep numbness) changes at 12 months. The secondary outcomes were NIS and sensory nerve conduction test result.

Results: Of 391 eligible patients, 300 were recruited (130 [43.3%] male; mean [SD] age, 57.6 [8.9] years; mean [SD] duration of diabetes, 11.4 [7.8] years) and 229 (76.3%) completed the trial. The TSS changes between the tocotrienols and placebo groups at 12 months (-0.30; 95% CI, -1.16 to 0.56; P = .49) were similar. No significant differences in NIS (0.60; 95% CI, -1.37 to 2.65; P = .53) and sensory nerve conduction test assessments were found between both groups. In post hoc subgroup analyses, tocotrienols reduced lancinating pain among patients with hemoglobin A1C levels greater than 8% (P = .03) and normohomocysteinemia (homocysteine level <2.03 mg/L; P = .008) at 1 year. Serious adverse events in both groups were similar, except more infections were observed in the tocotrienols group (6.7% vs 0.7%, P = .04). Results reported were of modified intention-to-treat analyses.

Conclusions and Relevance: Supplementation of oral mixed tocotrienols, 400 mg/d for 1 year, did not improve overall neuropathic symptoms. The preliminary observations on lancinating pain among subsets of patients require further exploration.