Efficacy and Safety of Ornithine Phenylacetate for Treating Overt Hepatic Encephalopathy in a Randomized Trial
Copyright © 2021 by the AGA Institute. Published by Elsevier, Inc. Published by Elsevier Inc. All rights reserved..
BACKGROUND & AIMS: Hepatic encephalopathy (HE) is associated with increased morbidity, mortality, and health care resource use. In this phase 2b study, we evaluated the efficacy and safety of ornithine phenylacetate (OP), an ammonia scavenger, in hospitalized patients with cirrhosis, increased levels of ammonia at screening, and acute or overt HE.
METHODS: We conducted a double-blind study of 231 patients with cirrhosis and HE at multiple sites in North America, Europe, Israel, and Australia from January 7, 2014, through December 29, 2016. Patients were assigned randomly to groups that received placebo or OP (10, 15, or 20 g/d, based on the severity of liver disease), plus each institution's standard of care (eg, lactulose to achieve 2-3 bowel movements with or without rifaximin, in accordance with guidelines). The primary end point was time to confirmed clinical response, defined as reduction to HE staging tool (HEST) stage 2 from baseline HEST stages 3/4 or improvement to HEST stages 0/1 from baseline stage 2, in the intent-to-treat population (all patients with increased levels of ammonia at screening, determined by a local laboratory).
RESULTS: Median times to clinical improvement, based on ammonia measurements at local laboratories, did not differ significantly between the groups given OP vs the placebo group (P = .129). Analyses of central laboratory-confirmed increases in levels of ammonia at baseline (n = 201) showed clinical improvement in HE at a median of 21 hours sooner in groups given OP vs placebo. The percentages of patients with any specific adverse event did not differ significantly between groups. Serious adverse events occurred in 25% of patients in the OP group and in 29% in the placebo group (P = .552).
CONCLUSIONS: In a randomized controlled trial of patients with cirrhosis and HE, we found no significant difference in time to clinical improvement between patients given OP vs placebo. However, OP appears to be safe and should undergo further testing for treatment of hyperammonemia in hospitalized patients receiving treatment for the underlying precipitant of acute or overt HE. ClinicalTrials.gov no: NCT01966419.
| Errataetall: |
CommentIn: Clin Gastroenterol Hepatol. 2020 Nov 3;:null. - PMID 33157316 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
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| Enthalten in: |
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association - 19(2021), 12 vom: 01. Dez., Seite 2626-2635.e7 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rahimi, Robert S [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 24.01.2022 Date Revised 24.01.2022 published: Print-Electronic ClinicalTrials.gov: NCT01966419 CommentIn: Clin Gastroenterol Hepatol. 2020 Nov 3;:null. - PMID 33157316 Citation Status MEDLINE |
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| doi: |
10.1016/j.cgh.2020.10.019 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM316393134 |
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| 245 | 1 | 0 | |a Efficacy and Safety of Ornithine Phenylacetate for Treating Overt Hepatic Encephalopathy in a Randomized Trial |
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| 500 | |a Date Revised 24.01.2022 | ||
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| 500 | |a ClinicalTrials.gov: NCT01966419 | ||
| 500 | |a CommentIn: Clin Gastroenterol Hepatol. 2020 Nov 3;:null. - PMID 33157316 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 by the AGA Institute. Published by Elsevier, Inc. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND & AIMS: Hepatic encephalopathy (HE) is associated with increased morbidity, mortality, and health care resource use. In this phase 2b study, we evaluated the efficacy and safety of ornithine phenylacetate (OP), an ammonia scavenger, in hospitalized patients with cirrhosis, increased levels of ammonia at screening, and acute or overt HE | ||
| 520 | |a METHODS: We conducted a double-blind study of 231 patients with cirrhosis and HE at multiple sites in North America, Europe, Israel, and Australia from January 7, 2014, through December 29, 2016. Patients were assigned randomly to groups that received placebo or OP (10, 15, or 20 g/d, based on the severity of liver disease), plus each institution's standard of care (eg, lactulose to achieve 2-3 bowel movements with or without rifaximin, in accordance with guidelines). The primary end point was time to confirmed clinical response, defined as reduction to HE staging tool (HEST) stage 2 from baseline HEST stages 3/4 or improvement to HEST stages 0/1 from baseline stage 2, in the intent-to-treat population (all patients with increased levels of ammonia at screening, determined by a local laboratory) | ||
| 520 | |a RESULTS: Median times to clinical improvement, based on ammonia measurements at local laboratories, did not differ significantly between the groups given OP vs the placebo group (P = .129). Analyses of central laboratory-confirmed increases in levels of ammonia at baseline (n = 201) showed clinical improvement in HE at a median of 21 hours sooner in groups given OP vs placebo. The percentages of patients with any specific adverse event did not differ significantly between groups. Serious adverse events occurred in 25% of patients in the OP group and in 29% in the placebo group (P = .552) | ||
| 520 | |a CONCLUSIONS: In a randomized controlled trial of patients with cirrhosis and HE, we found no significant difference in time to clinical improvement between patients given OP vs placebo. However, OP appears to be safe and should undergo further testing for treatment of hyperammonemia in hospitalized patients receiving treatment for the underlying precipitant of acute or overt HE. ClinicalTrials.gov no: NCT01966419 | ||
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| 650 | 4 | |a Altered Mental Status | |
| 650 | 4 | |a Liver Fibrosis | |
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| 700 | 1 | |a Bhamidimarri, Kalyan Ram |e verfasserin |4 aut | |
| 700 | 1 | |a Pyrsopoulos, Nikolaos |e verfasserin |4 aut | |
| 700 | 1 | |a Potthoff, Amy |e verfasserin |4 aut | |
| 700 | 1 | |a Bukofzer, Stan |e verfasserin |4 aut | |
| 700 | 1 | |a Bajaj, Jasmohan S |e verfasserin |4 aut | |
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