TY - JOUR
T1 - Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study)
T2 - A randomised controlled trial
AU - De Zeeuw, Dick
AU - Agarwal, Rajiv
AU - Amdahl, Michael
AU - Audhya, Paul
AU - Coyne, Daniel
AU - Garimella, Tushar
AU - Parving, Hans Henrik
AU - Pritchett, Yili
AU - Remuzzi, Giuseppe
AU - Ritz, Eberhard
AU - Andress, Dennis
N1 - Funding Information:
We thank the investigators, local study coordinators, and patients for their valuable contributions to this study; Jin Tian for contribution to the study design; Shihua Wen, employee of Abbott, for statistical programming support; and Amanda J Fein, employee of Abbott, for medical writing support. Funding for this study, including travel and accommodation expenses for study meetings and honoraria for the steering committee, was provided by Abbott.
PY - 2010/11/6
Y1 - 2010/11/6
N2 - Background: Despite treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors, patients with diabetes have increased risk of progressive renal failure that correlates with albuminuria. We aimed to assess whether paricalcitol could be used to reduce albuminuria in patients with diabetic nephropathy. Methods: In this multinational, placebo-controlled, double-blind trial, we enrolled patients with type 2 diabetes and albuminuria who were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Patients were assigned (1:1:1) by computer-generated randomisation sequence to receive 24 weeks' treatment with placebo, 1 μg/day paricalcitol, or 2 μg/day paricalcitol. The primary endpoint was the percentage change in geometric mean urinary albumin-to-creatinine ratio (UACR) from baseline to last measurement during treatment for the combined paricalcitol groups versus the placebo group. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00421733. Findings: Between February, 2007, and October, 2008, 281 patients were enrolled and assigned to receive placebo (n=93), 1 μg paricalcitol (n=93), or 2 μg paricalcitol (n=95); 88 patients on placebo, 92 on 1 μg paricalcitol, and 92 on 2 μg paricalcitol received at least one dose of study drug, and had UACR data at baseline and at least one timepoint during treatment, and so were included in the primary analysis. Change in UACR was: -3% (from 61 to 60 mg/mmol; 95% CI -16 to 13) in the placebo group; -16 (from 62 to 51 mg/mmol; -24 to -9) in the combined paricalcitol groups, with a between-group difference versus placebo of -15 (95% CI -28 to 1; p=0·071); -14% (from 63 to 54 mg/mmol; -24 to -1) in the 1 μg paricalcitol group, with a between-group difference versus placebo of -11% (95 CI -27 to 8; p=0·23); and -20% (from 61 to 49 mg/mmol; -30 to -8) in the 2 μg paricalcitol group, with a between-group difference versus placebo of -18% (95 CI -32 to 0; p=0·053). Patients on 2 μg paricalcitol showed an early, sustained reduction in UACR, ranging from -18 to -28 (p=0·014 vs placebo). Incidence of hypercalcaemia, adverse events, and serious adverse events was similar between groups receiving paricalcitol versus placebo. Interpretation: Addition of 2 μg/day paricalcitol to RAAS inhibition safely lowers residual albuminuria in patients with diabetic nephropathy, and could be a novel approach to lower residual renal risk in diabetes. Funding: Abbott.
AB - Background: Despite treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors, patients with diabetes have increased risk of progressive renal failure that correlates with albuminuria. We aimed to assess whether paricalcitol could be used to reduce albuminuria in patients with diabetic nephropathy. Methods: In this multinational, placebo-controlled, double-blind trial, we enrolled patients with type 2 diabetes and albuminuria who were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Patients were assigned (1:1:1) by computer-generated randomisation sequence to receive 24 weeks' treatment with placebo, 1 μg/day paricalcitol, or 2 μg/day paricalcitol. The primary endpoint was the percentage change in geometric mean urinary albumin-to-creatinine ratio (UACR) from baseline to last measurement during treatment for the combined paricalcitol groups versus the placebo group. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00421733. Findings: Between February, 2007, and October, 2008, 281 patients were enrolled and assigned to receive placebo (n=93), 1 μg paricalcitol (n=93), or 2 μg paricalcitol (n=95); 88 patients on placebo, 92 on 1 μg paricalcitol, and 92 on 2 μg paricalcitol received at least one dose of study drug, and had UACR data at baseline and at least one timepoint during treatment, and so were included in the primary analysis. Change in UACR was: -3% (from 61 to 60 mg/mmol; 95% CI -16 to 13) in the placebo group; -16 (from 62 to 51 mg/mmol; -24 to -9) in the combined paricalcitol groups, with a between-group difference versus placebo of -15 (95% CI -28 to 1; p=0·071); -14% (from 63 to 54 mg/mmol; -24 to -1) in the 1 μg paricalcitol group, with a between-group difference versus placebo of -11% (95 CI -27 to 8; p=0·23); and -20% (from 61 to 49 mg/mmol; -30 to -8) in the 2 μg paricalcitol group, with a between-group difference versus placebo of -18% (95 CI -32 to 0; p=0·053). Patients on 2 μg paricalcitol showed an early, sustained reduction in UACR, ranging from -18 to -28 (p=0·014 vs placebo). Incidence of hypercalcaemia, adverse events, and serious adverse events was similar between groups receiving paricalcitol versus placebo. Interpretation: Addition of 2 μg/day paricalcitol to RAAS inhibition safely lowers residual albuminuria in patients with diabetic nephropathy, and could be a novel approach to lower residual renal risk in diabetes. Funding: Abbott.
UR - http://www.scopus.com/inward/record.url?scp=78149359262&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(10)61032-X
DO - 10.1016/S0140-6736(10)61032-X
M3 - Article
C2 - 21055801
AN - SCOPUS:78149359262
SN - 0140-6736
VL - 376
SP - 1543
EP - 1551
JO - The Lancet
JF - The Lancet
IS - 9752
ER -