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Randomized placebo‐controlled trial of losartan for pediatric NAFLD
Author(s) -
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.
Publication year - 2022
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.32403
Subject(s) - losartan , medicine , placebo , randomized controlled trial , gastroenterology , blood pressure , angiotensin ii , pathology , alternative medicine
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.