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Randomized placebo‐controlled trial of losartan for pediatric NAFLD
BACKGROUND AND AIMS: To date, no pharmacotherapy exists for pediatric NAFLD. Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its antifibrotic effects. APPROACH AND RESULTS: The Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, doubl...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288975/ https://www.ncbi.nlm.nih.gov/pubmed/35133671 http://dx.doi.org/10.1002/hep.32403 |
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author | Vos, Miriam B. Van Natta, Mark L. Blondet, Niviann M. Dasarathy, Srinivasan Fishbein, Mark Hertel, Paula Jain, Ajay K. Karpen, Saul J. Lavine, Joel E. Mohammad, Saeed Miriel, Laura A. Molleston, Jean P. Mouzaki, Marialena Sanyal, Arun Sharkey, Emily P. Schwimmer, Jeffrey B. Tonascia, James Wilson, Laura A. Xanthakos, Stavra A. |
author_facet | Vos, Miriam B. Van Natta, Mark L. Blondet, Niviann M. Dasarathy, Srinivasan Fishbein, Mark Hertel, Paula Jain, Ajay K. Karpen, Saul J. Lavine, Joel E. Mohammad, Saeed Miriel, Laura A. Molleston, Jean P. Mouzaki, Marialena Sanyal, Arun Sharkey, Emily P. Schwimmer, Jeffrey B. Tonascia, James Wilson, Laura A. Xanthakos, Stavra A. |
author_sort | Vos, Miriam B. |
collection | PubMed |
description | BACKGROUND AND AIMS: To date, no pharmacotherapy exists for pediatric NAFLD. Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its antifibrotic effects. APPROACH AND RESULTS: The Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, double‐masked, placebo‐controlled, randomized clinical trial in children with histologically confirmed NAFLD at 10 sites (September 2018 to April 2020). Inclusion criteria were age 8–17 years, histologic NAFLD activity score ≥ 3, and serum alanine aminotransferase (ALT) ≥ 50 U/l. Children received 100 mg of losartan or placebo orally once daily for 24 weeks. The primary outcome was change in ALT levels from baseline to 24 weeks, and the preset sample size was n = 110. Treatment effects were assessed using linear regression of change in treatment group adjusted for baseline value. Eighty‐three participants (81% male, 80% Hispanic) were randomized to losartan (n = 43) or placebo (n = 40). During an enrollment pause, necessitated by the 2019 coronavirus pandemic, an unplanned interim analysis showed low probability (7%) of significant group difference. The Data and Safety Monitoring Board recommended early study termination. Baseline characteristics were similar between groups. The 24‐week change in ALT did not differ significantly between losartan versus placebo groups (adjusted mean difference: 1.1 U/l; 95% CI = −30.6, 32.7; p = 0.95), although alkaline phosphatase decreased significantly in the losartan group (adjusted mean difference: −23.4 U/l; 95% CI = −41.5, −5.3; p = 0.01). Systolic blood pressure decreased in the losartan group but increased in placebo (adjusted mean difference: −7.5 mm Hg; 95% CI = −12.2, −2.8; p = 0.002). Compliance by pill counts and numbers and types of adverse events did not differ by group. CONCLUSIONS: Losartan did not significantly reduce ALT in children with NAFLD when compared with placebo. |
format | Online Article Text |
id | pubmed-9288975 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92889752022-10-14 Randomized placebo‐controlled trial of losartan for pediatric NAFLD Vos, Miriam B. Van Natta, Mark L. Blondet, Niviann M. Dasarathy, Srinivasan Fishbein, Mark Hertel, Paula Jain, Ajay K. Karpen, Saul J. Lavine, Joel E. Mohammad, Saeed Miriel, Laura A. Molleston, Jean P. Mouzaki, Marialena Sanyal, Arun Sharkey, Emily P. Schwimmer, Jeffrey B. Tonascia, James Wilson, Laura A. Xanthakos, Stavra A. Hepatology Original Articles BACKGROUND AND AIMS: To date, no pharmacotherapy exists for pediatric NAFLD. Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its antifibrotic effects. APPROACH AND RESULTS: The Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, double‐masked, placebo‐controlled, randomized clinical trial in children with histologically confirmed NAFLD at 10 sites (September 2018 to April 2020). Inclusion criteria were age 8–17 years, histologic NAFLD activity score ≥ 3, and serum alanine aminotransferase (ALT) ≥ 50 U/l. Children received 100 mg of losartan or placebo orally once daily for 24 weeks. The primary outcome was change in ALT levels from baseline to 24 weeks, and the preset sample size was n = 110. Treatment effects were assessed using linear regression of change in treatment group adjusted for baseline value. Eighty‐three participants (81% male, 80% Hispanic) were randomized to losartan (n = 43) or placebo (n = 40). During an enrollment pause, necessitated by the 2019 coronavirus pandemic, an unplanned interim analysis showed low probability (7%) of significant group difference. The Data and Safety Monitoring Board recommended early study termination. Baseline characteristics were similar between groups. The 24‐week change in ALT did not differ significantly between losartan versus placebo groups (adjusted mean difference: 1.1 U/l; 95% CI = −30.6, 32.7; p = 0.95), although alkaline phosphatase decreased significantly in the losartan group (adjusted mean difference: −23.4 U/l; 95% CI = −41.5, −5.3; p = 0.01). Systolic blood pressure decreased in the losartan group but increased in placebo (adjusted mean difference: −7.5 mm Hg; 95% CI = −12.2, −2.8; p = 0.002). Compliance by pill counts and numbers and types of adverse events did not differ by group. CONCLUSIONS: Losartan did not significantly reduce ALT in children with NAFLD when compared with placebo. John Wiley and Sons Inc. 2022-02-28 2022-08 /pmc/articles/PMC9288975/ /pubmed/35133671 http://dx.doi.org/10.1002/hep.32403 Text en © 2022 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Vos, Miriam B. Van Natta, Mark L. Blondet, Niviann M. Dasarathy, Srinivasan Fishbein, Mark Hertel, Paula Jain, Ajay K. Karpen, Saul J. Lavine, Joel E. Mohammad, Saeed Miriel, Laura A. Molleston, Jean P. Mouzaki, Marialena Sanyal, Arun Sharkey, Emily P. Schwimmer, Jeffrey B. Tonascia, James Wilson, Laura A. Xanthakos, Stavra A. Randomized placebo‐controlled trial of losartan for pediatric NAFLD |
title | Randomized placebo‐controlled trial of losartan for pediatric NAFLD |
title_full | Randomized placebo‐controlled trial of losartan for pediatric NAFLD |
title_fullStr | Randomized placebo‐controlled trial of losartan for pediatric NAFLD |
title_full_unstemmed | Randomized placebo‐controlled trial of losartan for pediatric NAFLD |
title_short | Randomized placebo‐controlled trial of losartan for pediatric NAFLD |
title_sort | randomized placebo‐controlled trial of losartan for pediatric nafld |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288975/ https://www.ncbi.nlm.nih.gov/pubmed/35133671 http://dx.doi.org/10.1002/hep.32403 |
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