Abstract | BACKGROUND: METHODS: We did this randomised, crossover trial in two hospitals in Italy. Eligibility criteria were: age 18 years or older, urinary albumin excretion 20-999 μg/min, systolic blood pressure (BP) less than 140 mm Hg, and diastolic BP less than 90 mm Hg. Patients were randomly assigned (1:1) with a computer-generated randomised sequence to receive either daglutril (300 mg/day) then placebo for 8 weeks each or vice versa, with a 4-week washout period. Patients also took losartan throughout. Participants and investigators were masked to treatment allocation. The primary endpoint was 24-h urinary albumin excretion in the intention-to-treat population. Secondary endpoints were median office and ambulatory (24 h, daytime, and night-time) BP, renal haemodynamics and sieving function, and metabolic and laboratory test results. This study is registered with ClinicalTrials.gov, number NCT00160225. FINDINGS: We screened 58 patients, of whom 45 were enrolled (22 assigned to daglutril then placebo, 23 to placebo then daglutril; enrolment from May, 2005, to December, 2006) and 42 (20 vs 22) were included in the primary analysis. Daglutril did not significantly affect 24-h urinary albumin excretion compared with placebo (difference in change -7·6 μg/min, IQR -78·7 to 19·0; p=0·559). 34 patients had complete 24-h BP readings; compared with placebo, daglutril significantly reduced 24-h systolic (difference -5·2 mm Hg, SD 9·4; p=0·0013), diastolic (-2·5, 6·2; p=0·015), pulse (-3·0, 6·3; p=0·019), and mean (-3·1, 6·2; p=0·003) BP, as well as all night-time BP readings and daytime systolic, pulse, and mean BP, but not diastolic BP. Compared with placebo, daglutril also significantly reduced office systolic BP (-5·4, 15·4; p=0·028), but not diastolic (-1·8, 9·9; p=0·245), pulse (-3·1, 10·6; p=0·210), or mean (-2·1, 10·4; p=0·205) BP, and increased big endothelin serum concentration. Other secondary outcomes did not differ significantly between treatment periods. Three patients taking placebo and six patients taking daglutril had mild treatment-related adverse events--the most common was facial or peripheral oedema (in four patients taking daglutril). INTERPRETATION: FUNDING:
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Authors | Aneliya Parvanova, Irene M van der Meer, Ilian Iliev, Annalisa Perna, Flavio Gaspari, Roberto Trevisan, Antonio Bossi, Giuseppe Remuzzi, Ariela Benigni, Piero Ruggenenti, Daglutril in Diabetic Nephropathy Study Group |
Journal | The lancet. Diabetes & endocrinology
(Lancet Diabetes Endocrinol)
Vol. 1
Issue 1
Pg. 19-27
(Sep 2013)
ISSN: 2213-8595 [Electronic] England |
PMID | 24622263
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 Elsevier Ltd. All rights reserved. |
Chemical References |
- Benzazepines
- Enzyme Inhibitors
- SLV 306
- Aspartic Acid Endopeptidases
- Metalloendopeptidases
- Neprilysin
- Endothelin-Converting Enzymes
|
Topics |
- Aged
- Albuminuria
(drug therapy, enzymology, epidemiology)
- Aspartic Acid Endopeptidases
(antagonists & inhibitors, metabolism)
- Benzazepines
(pharmacology, therapeutic use)
- Blood Pressure
(drug effects, physiology)
- Cross-Over Studies
- Diabetes Mellitus, Type 2
(drug therapy, enzymology, epidemiology)
- Double-Blind Method
- Endothelin-Converting Enzymes
- Enzyme Inhibitors
(pharmacology, therapeutic use)
- Female
- Humans
- Male
- Metalloendopeptidases
(antagonists & inhibitors, metabolism)
- Middle Aged
- Neprilysin
(antagonists & inhibitors, metabolism)
- Prospective Studies
- Treatment Outcome
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