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Randomized placebo-controlled trial of losartan for pediatric NAFLD.

Authors :: Vos MB
Van Natta ML
Blondet NM
Dasarathy S
Fishbein M
Hertel P
Jain AK
Karpen SJ
Lavine JE
Mohammad S
Miriel LA
Molleston JP
Mouzaki M
Sanyal A
Sharkey EP
Schwimmer JB
Tonascia J
Wilson LA
Xanthakos SA
Source :: Hepatology (Baltimore, Md.) [Hepatology] 2022 Aug; Vol. 76 (2), pp. 429-444. Date of Electronic Publication: 2022 Feb 28.
Publication Year :: 2022
Abstract: 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.<br />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.<br />Conclusions: Losartan did not significantly reduce ALT in children with NAFLD when compared with placebo.<br /> (© 2022 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)