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2018 ; 33
(3
): 477-489
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gab.com Text
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English Wikipedia
Multicenter, open-label, extension trial to evaluate the long-term efficacy and
safety of early versus delayed treatment with tolvaptan in autosomal dominant
polycystic kidney disease: the TEMPO 4:4 Trial
#MMPMID28379536
Torres VE
; Chapman AB
; Devuyst O
; Gansevoort RT
; Perrone RD
; Dandurand A
; Ouyang J
; Czerwiec FS
; Blais JD
Nephrol Dial Transplant
2018[Mar]; 33
(3
): 477-489
PMID28379536
show ga
BACKGROUND: In TEMPO 3:4, the vasopressin V2 receptor antagonist tolvaptan slowed
total kidney volume (TKV) growth and estimated glomerular filtration rate (eGFR)
decline relative to placebo. METHODS: TEMPO 4:4 was designed to provide an
additional 2 years of data on the long-term safety and efficacy of tolvaptan in
subjects completing TEMPO 3:4. The objective was to assess the disease-modifying
effects of tolvaptan on TKV and eGFR end-points including change from baseline
over the combined duration of TEMPO 3:4 and TEMPO 4:4, and non-inferiority of
slopes during TEMPO 4:4. RESULTS: Of the 1445 subjects randomized to TEMPO 3:4,
871 (60.3%) enrolled in TEMPO 4:4. Percent changes in TKV from TEMPO 3:4 baseline
to TEMPO 4:4 Month 24 were 29.9% and 31.6% (prior tolvaptan versus prior placebo,
P?=?0.38). Adjusting for baseline covariates improved the TKV treatment
difference at Month 24 in TEMPO 4:4 from -1.70% to?-?4.15% between the groups
(P?=?0.04). Slopes of TKV growth during TEMPO 4:4 were higher in early- versus
delayed-treatment groups (6.16% versus 4.96% per year, P?=?0.05). Analysis of
secondary eGFR endpoints demonstrated a persistent effect on eGFR
(3.15?mL/min/1.73 m2, P?0.001), and non-inferiority in eGFR slopes. The safety
profile on exposure to tolvaptan in TEMPO 4:4 was similar to that in TEMPO 3:4.
CONCLUSIONS: The results of TEMPO 4:4 support a sustained disease-modifying
effect of tolvaptan on eGFR. The lack of a sustained treatment difference on TKV
may be accounted for by limitations of the trial design, including loss of
randomization and baseline imbalances ensuing TEMPO 3:4. The safety profile was
similar to that observed in TEMPO 3:4.
|*Time-to-Treatment
[MESH]
|Adult
[MESH]
|Antidiuretic Hormone Receptor Antagonists/*therapeutic use
[MESH]