Impact of ornithine phenylacetate (OCR-002) in lowering plasma ammonia after upper gastrointestinal bleeding in cirrhotic patients.
BACKGROUND
Ornithine phenylacetate (OP) has been proven effective in lowering ammonia plasma levels in animals, and to be well tolerated in cirrhotic patients. A trial to assess OP efficacy in lowering plasma ammonia levelsversusplacebo in cirrhotic patients after an upper gastrointestinal bleeding was performed. The primary outcome was a decrease in venous plasma ammonia at 24 hours.


METHODS
A total of 38 consecutive cirrhotic patients were enrolled within 24 hours of an upper gastrointestinal bleed. Patients were randomized (1:1) to receive OP (10 g/day) or glucosaline for 5 days.


RESULTS
The primary outcome was not achieved. A progressive decrease in ammonia was observed in both groups, being slightly greater in the OP group, with significant differences only at 120 hours. The subanalysis according to Child-Pugh score showed a statistically significant ammonia decrease in Child-Pugh C-treated patients at 36 hours, as well as in the time-normalized area under the curve (TN-AUC) 0-120 hours in the OP group [40.16 μmol/l (37.7-42.6); median (interquartile range) (IQR)]versusplacebo group [65.5 μmol/l (54-126);p= 0.036]. A decrease in plasma glutamine levels was observed in the treated group compared with the placebo group, and was associated with the appearance of phenylacetylglutamine in urine. Adverse-event frequency was similar in both groups. No differences in hepatic encephalopathy incidence were observed.


CONCLUSIONS
OP failed to significantly decrease plasma ammonia at the given doses (10 g/day). Higher doses of OP might be required in Child-Pugh A and B patients. OP appeared well tolerated.
Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Research and Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Meritxell
M
Ventura-Cots
Department of Medicine, Universitat Autònoma de Barcelona and Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Institut d'investigacions biomèdiques Sant Pau, Barcelona, Spain.
Mar
M
Concepción
Laboratory of Metabolic Diseases, Hospital Universitari Vall d'Hebron, Spain.
José Antonio
JA
Arranz
Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Research and Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Macarena
M
Simón-Talero
Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Research, Barcelona, Spain.
Maria
M
Torrens
Laboratory of Metabolic Diseases, Hospital Universitari Vall d'Hebron, Spain.
Albert
A
Blanco-Grau
Clinical Research Support Unit, Vall d'Hebron Institut of Research, UK.
Inma
I
Fuentes
Pharmacy Department, Hospital Universitari Vall d'Hebron, Spain.
Pilar
P
Suñé
Department of Medicine, Universitat Autònoma de Barcelona and Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques Sant Pau, Barcelona, Spain.
Edilmar
E
Alvarado-Tapias
Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques Sant Pau, Barcelona, Spain.
Cristina
C
Gely
Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques Sant Pau, Barcelona, Spain.
Eva
E
Roman
Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Research and Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
Beatriz
B
Mínguez
Department of Medicine, Universitat Autònoma de Barcelona and Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques Sant Pau, Barcelona, Spain CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
German
G
Soriano
Liver Unit, Hospital Universitari Vall d'Hebron, Department of Medicine, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Joan
J
Genescà
Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Research and Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
Juan
J
Córdoba
ammonia; cirrhosis; hepatic encephalopathy; ornithine phenylacetate; upper gastrointestinal bleeding