10.6084/m9.figshare.4626220.v1
Torres V.E.
Torres
V.E.
Devuyst O.
Devuyst
O.
Chapman A.B.
Chapman
A.B.
Gansevoort R.T.
Gansevoort
R.T.
Perrone R.D.
Perrone
R.D.
Ouyang J.
Ouyang
J.
Blais J.D.
Blais
J.D.
Czerwiec F.S.
Czerwiec
F.S.
Sergeyeva O.
Sergeyeva
O.
for the REPRISE Trial Investigators
for the REPRISE Trial
Investigators
PowerPoint Slides for: Rationale and Design of a Clinical Trial Investigating Tolvaptan Safety and Efficacy in Autosomal Dominant Polycystic Kidney Disease
Karger Publishers
2017
Autosomal dominant polycystic kidney disease
Chronic kidney disease
Vasopressin
Vasopressin receptor antagonist
V2 receptor antagonist
randomized clinical trial
2017-02-07 15:12:47
Dataset
https://karger.figshare.com/articles/dataset/PowerPoint_Slides_for_Rationale_and_Design_of_a_Clinical_Trial_Investigating_Tolvaptan_Safety_and_Efficacy_in_Autosomal_Dominant_Polycystic_Kidney_Disease/4626220
<p><b><i>Background:</i></b> In TEMPO 3:4, the vasopressin V2-receptor
antagonist tolvaptan slowed kidney growth and function decline in
autosomal dominant polycystic kidney disease (ADPKD) patients with
relatively preserved kidney function. <b><i>Methods:</i></b>
Prospective, phase 3b, multi-center, randomized-withdrawal,
placebo-controlled, double-blind trial of tolvaptan in ADPKD patients
with late stage 2 to early stage 4 chronic kidney disease (CKD). The
primary endpoint was estimated glomerular filtration rate (eGFR) change
from pre-treatment baseline to post-treatment follow-up. Secondary
endpoints included annualized eGFR slope, incidence of ADPKD
complications, and overall and hepatic safety profiles. Participants
were 18-55 year-old ADPKD patients with baseline eGFR ≥25 and ≤65
mL/min/1.73 m<sup>2</sup> or 56-65 year-old with eGFR ≥25 and ≤44 mL/min/1.73 m<sup>2</sup> and evidence of eGFR decline >2.0 mL/min/1.73 m<sup>2</sup>
per year. Daily split doses of tolvaptan were titrated to tolerance
(30/15, 45/15, 60/30, or 90/30 mg) and maintained for 12 months, after
an 8-week pre-randomization period to screen out subjects unable to
tolerate at least 60/30 mg for 3 weeks. <b><i>Results:</i></b> Of 1,495
subjects who entered the tolvaptan titration period, 125 (8.4%)
discontinued the study before randomization. One thousand three hundred
seventy subjects (684 tolvaptan, 686 placebo) from 213 centers across 21
countries were randomized. Baseline demographics were well balanced
across treatment arms. Information collected during the study included
eGFR, survey scores (PKD history and outcome), adverse events, vital
signs, hematology, urinalysis, and serum chemistry tests. <b><i>Conclusion:</i></b>
Replicating Evidence of Preserved Renal Function: An Investigation of
Tolvaptan Safety and Efficacy (REPRISE) determines whether tolvaptan
administered over 1 year exhibits disease-modifying properties in ADPKD
patients with late stage 2 to early stage 4 CKD, which provides an
important therapeutic advancement for this difficult-to-treat disease.</p>