UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease

Torres, VE; Chapman, AB; Devuyst, O; Gansevoort, RT; Perrone, RD; Koch, G; Ouyang, J; ... REPRISE Trial Investigators, .; + view all (2017) Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease. New England Journal of Medicine , 377 (20) pp. 1930-1942. 10.1056/NEJMoa1710030. Green open access

[thumbnail of Published article]
Preview
Text (Published article)
nejmoa1710030.pdf - Published Version

Download (399kB) | Preview
[thumbnail of Supplementary Appendix]
Preview
Text (Supplementary Appendix)
nejmoa1710030_appendix.pdf

Download (512kB) | Preview
[thumbnail of Disclosure Forms]
Preview
Text (Disclosure Forms)
nejmoa1710030_disclosures.pdf

Download (168kB) | Preview
[thumbnail of Protocol]
Preview
Text (Protocol)
nejmoa1710030_protocol.pdf

Download (6MB) | Preview

Abstract

BACKGROUND: In a previous trial involving patients with early autosomal dominant polycystic kidney disease (ADPKD; estimated creatinine clearance, ≥60 ml per minute), the vasopressin V2-receptor antagonist tolvaptan slowed the growth in total kidney volume and the decline in the estimated glomerular filtration rate (GFR) but also caused more elevations in aminotransferase and bilirubin levels. The efficacy and safety of tolvaptan in patients with later-stage ADPKD are unknown. METHODS: We conducted a phase 3, randomized withdrawal, multicenter, placebo-controlled, double-blind trial. After an 8-week prerandomization period that included sequential placebo and tolvaptan run-in phases, during which each patient’s ability to take tolvaptan without dose-limiting side effects was assessed, 1370 patients with ADPKD who were either 18 to 55 years of age with an estimated GFR of 25 to 65 ml per minute per 1.73 m2 of body-surface area or 56 to 65 years of age with an estimated GFR of 25 to 44 ml per minute per 1.73 m2 were randomly assigned in a 1:1 ratio to receive tolvaptan or placebo for 12 months. The primary end point was the change in the estimated GFR from baseline to follow-up, with adjustment for the exact duration that each patient participated (interpolated to 1 year). Safety assessments were conducted monthly. RESULTS: The change from baseline in the estimated GFR was −2.34 ml per minute per 1.73 m2 (95% confidence interval [CI], −2.81 to −1.87) in the tolvaptan group, as compared with −3.61 ml per minute per 1.73 m2 (95% CI, −4.08 to −3.14) in the placebo group (difference, 1.27 ml per minute per 1.73 m2; 95% CI, 0.86 to 1.68; P<0.001). Elevations in the alanine aminotransferase level (to >3 times the upper limit of the normal range) occurred in 38 of 681 patients (5.6%) in the tolvaptan group and in 8 of 685 (1.2%) in the placebo group. Elevations in the aminotransferase level were reversible after stopping tolvaptan. No elevations in the bilirubin level of more than twice the upper limit of the normal range were detected. CONCLUSIONS: Tolvaptan resulted in a slower decline than placebo in the estimated GFR over a 1-year period in patients with later-stage ADPKD. (Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization; REPRISE ClinicalTrials.gov number, NCT02160145.)

Type: Article
Title: Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease
Open access status: An open access version is available from UCL Discovery
DOI: 10.1056/NEJMoa1710030
Publisher version: http://dx.doi.org/10.1056/NEJMoa1710030
Language: English
Additional information: This is the published version of record. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10050941
Downloads since deposit
431Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item