Semi-individualised Chinese Medicine Treatment as an Adjuvant Management for Diabetic Nephropathy – Preliminary results of an add-on, randomised, controlled, multi-centre, open-label pragmatic trial

Abstract

Background: Conventional treatment for diabetic nephropathy (DN) has achieved limited effect in preserving renal function. Recent big data studies showed that Chinese medicine (CM) could reduce the risk of end-stage kidney disease by 59% percent in a 6-year period. However, existing CM clinical guidelines are weakly evidence-based and the effect of combined Chinese and conventional medicine remains unclear. Methods: This assessor-blind, add-on, randomized, controlled, multi-center, openlabel pilot pragmatic trial evaluates the effect of an add-on semi-individualized CM treatment protocol based on expert consensus. 148 DN patients are being recruited and randomized 1:1 to a 48-week add-on semi-individualized CM treatment or standard medical care. Primary endpoints are changes in estimated glomerular filtration rate (GFR) and spot urine albumin-to-creatinine ratio (UACR) between baseline and endpoint. Outcomes are analyzed as intention-to-treat by regression models. Results: Recruitment started in July 2015. First 25 patients have completed 24 weeks of study period. The groups are similar for demographics. Mean GFR of intervention and control group decreased by 0.06 and 3.51 mL/min/1.73m2 respectively (95% CI: -8.08 to 1.19). Mean UACR of intervention and control group increased by 44% and 28% respectively (95% CI: -88.5% to 57%). After adjusting for age, gender, baseline HbA1c, BMI, blood pressures, GFR and UACR, intervention contributes to 3.8 mL/min/1.73m2 increase (95% CI: -3.9 to 11.4, p=0.30) in 24-week mean GFR in treatment group versus control (47.5 vs 43.8). The model explains 88% of variability and contribution remains similar (mean diff.: 4.1, 95%CI: -4.0 to 12.2, p=0.28) when 24-week UACR is adjusted in sensitivity analysis. Adjusted 24-week mean UACR, HbA1c, blood pressures, AST, ALT levels, and incidence of serious adverse events are comparable between groups. Conclusions: Our interim analysis suggests that add-on semi-individualized CM treatment may stabilize GFR among DN patients with macroalbuminuria independent of albuminuria, glycemic and blood pressure control. Funding: Health and Medical Research Fund (Ref:12133341)