phenylacetic acid and Liver Failure, Acute studies

phenylacetic acid : A monocarboxylic acid that is toluene in which one of the hydrogens of the methyl group has been replaced by a carboxy group.

Liver Failure, Acute: A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C.

Research Excerpts

Excerpt	Relevance	Reference
"L-Ornithine and phenylacetate act synergistically to successfully attenuate increases in arterial ammonia, which is accompanied by a significant decrease in extracellular brain ammonia and prevention of intracranial hypertension in pigs with ALF."	7.75	L-ornithine phenylacetate attenuates increased arterial and extracellular brain ammonia and prevents intracranial hypertension in pigs with acute liver failure. ( Cobos, MJ; Fuskevåg, OM; Jalan, R; Kalstad, T; Kristiansen, RG; Maehre, H; Revhaug, A; Rose, CF; Ytrebø, LM, 2009)
"L-Ornithine and phenylacetate act synergistically to successfully attenuate increases in arterial ammonia, which is accompanied by a significant decrease in extracellular brain ammonia and prevention of intracranial hypertension in pigs with ALF."	3.75	L-ornithine phenylacetate attenuates increased arterial and extracellular brain ammonia and prevents intracranial hypertension in pigs with acute liver failure. ( Cobos, MJ; Fuskevåg, OM; Jalan, R; Kalstad, T; Kristiansen, RG; Maehre, H; Revhaug, A; Rose, CF; Ytrebø, LM, 2009)

Research

Studies (1)

Authors

Clinical Trials (1)

Trial Overview

Trial Outcomes

Change in Ammonia

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	1 (100.00)	29.6817
2010's	0 (0.00)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Ytrebø, LM	1
Kristiansen, RG	1
Maehre, H	1
Fuskevåg, OM	1
Kalstad, T	1
Revhaug, A	1
Cobos, MJ	1
Jalan, R	1
Rose, CF	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Phase 2a Study to Evaluate the Safety and Tolerability of OCR-002 (Ornithine Phenylacetate) in the Treatment of Patients With Acute Liver Failure/Severe Acute Liver Injury[NCT01548690]	Phase 2	47 participants (Actual)	Interventional	2012-06-30	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

To evaluate the effect of OCR-002 on ammonia levels in patients with acute liver failure/severe acute liver injury (NCT01548690)
Timeframe: Baseline and 72 Hours

Measurement of OCR-002 Plasma Concentration

Intervention	Percent Change (Mean)
Maximum Dose Level 3.33 g/24h	41.2
Maximum Dose Level 6.65 g/24h	16.6
Maximum Dose Level 10 g/24h	41.8
Maximum Dose Level 20g/24h	38.4

To evaluate the steady state pharmacokinetic and pharmacodynamic profile of OCR-002 in patients with impaired and intact renal function using urinary phenylacetylglutamine (PAGN) as a surrogate marker (NCT01548690)
Timeframe: 24 Hours after last infusion

Neurological Function Measured by the Orientation Log (O-log)

Intervention	micrograms per millileter (Mean)
Maximum Dose Level 3.33 g/24h	65.6
Maximum Dose Level 6.65 g/24h	32.2
Maximum Dose Level 10 g/24h	33.4
Maximum Dose Level 20g/24h	104.9

The orientation log focuses on orientation to place, time, and circumstance. There are 10 items on the orientation log, which are scored 0-3. A spontaneous correct response is awarded 3 points. A spontaneous response that is lacking or incorrect, but a correct response is provided following a logical cue is awarded 2 points. A score of 1 is given if spontaneous and cued responses are lacking or incorrect, but a correct response is provided in a recognition format. A score of 0 is given if the spontaneous, cued, or recognition format does not generate a correct answer. Scores from the 10 items are summed and the final score ranges from 0 to 30. (NCT01548690)
Timeframe: 30 Days

Neurological Function Measured by the West Haven Criteria (WHC) for Hepatic Encephalopathy

Intervention	units on a scale (Mean)
Maximum Dose Level 3.33 g/24h	23.8
Maximum Dose Level 6.65 g/24h	24.0
Maximum Dose Level 10 g/24h	24.0
Maximum Dose Level 20g/24h	24.0

The West Haven Criteria (WHC) for Hepatic Encephalopathy measures the severity of encephalopathy and patient's level of consciousness. The scale ranges from 0 to 4; a minimum score of 0 represents a better outcome, and a maximum total score of 4 represents a worse outcome. A score of 0 corresponds to normal consciousness and behavior and normal neurological examination. A score of 1 corresponds to mild lack of awareness, shortened attention span, and impaired addition or subtraction; mild asterixis or tremor. A score of 2 corresponds to lethargy, disorientated or inappropriate behavior, obvious asterixis; slurred speech. A score of 3 corresponds to somnolent but arousable, gross disorientation or bizarre behavior, muscle rigidity and clonus; hyperreflexia. A score of 4 corresponds to coma and decerebrate posturing. (NCT01548690)
Timeframe: 120 hours from start of infusion

Number of Participants That do Not Tolerate the Administered Dose and Had Grade 3 or 4 Treatment Emergent Adverse Events as a Measure of Safety and Tolerability

Intervention	units on a scale (Mean)
Maximum Dose Level 3.33 g/24h	2.4
Maximum Dose Level 6.65 g/24h	3.2
Maximum Dose Level 10 g/24h	1.6
Maximum Dose Level 20g/24h	1.8

To evaluate the safety and tolerability of OCR-002 in patients with acute liver failure/severe acute liver injury (NCT01548690)
Timeframe: 30 Days

phenylacetic acid and Liver Failure, Acute