Acute Liver FailurePhase 2STOP-ALFNCT01548690
Safety Study of Ornithine Phenylacetate to Treat Patients With Acute Liver Failure/Severe Acute Liver Injury
A Phase 2 study testing Ornithine Phenylacetate in people with Acute Liver Failure and Acute Liver Injury, run by William Lee at 11 sites in United States.
Trial summary
This Phase 2a clinical study is designed to provide data on OCR-002 in patients with acute liver failure/acute liver injury (ALF/ALI) in regard to: safety and tolerability; metabolism of the compound to glutamine and phenylacetylglutamine (PAGN); its effect on circulating ammonia levels and neurological function in… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute Liver Failure, Acute Liver Injury
- What is being tested?
- Ornithine Phenylacetate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 11 sitesUnited States
- Study dates
- Jun 2012to 23 Feb 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women, ages 18-65 (have not reached their 66th birthday).
- Acute liver failure, defined as the development of coagulopathy (International normalized ratio [INR] ≥1.5) with encephalopathy in a patient with no prior history of liver disease, with onset of symptoms within 28 days of the inciting event. Patients may have either a history of acetaminophen overdose (defined as >4 g/day within 7 days of presentation) and/or detectable acetaminophen levels in the serum, with a pattern of liver function tests typical for acetaminophen toxicity (bilirubin < 10 mg/dL and alanine aminotransferase (ALT) ≥1000 IU/L), or a diagnosis of hepatitis A, hepatitis B, drug-induced liver injury, autoimmune hepatitis or indeterminate cause based on standard criteria.
- ALI patients may also be enrolled (those meeting the above criteria plus coagulopathy (INR ≥ 2.0) and no evidence of encephalopathy)
- Written informed consent from the patient (ALI) or patient's legally authorized representative or family member if he/she is considered encephalopathic (ALF).
- Ammonia level ≥60 μmol/L at baseline (within 8h prior to T0/initiation of infusion).
- Serum creatinine levels as follows:
Show all 9Show fewer
- Cohort 1: Creatinine ≤1.5 mg/dL; and
- Cohort 2: Creatinine >1.5 mg/dL and <10mg/dL.
- Mean arterial pressure of >65 mmHg.
Who cannot join
- History of chronic liver disease.
- Signs of overt cerebral herniation, or uncontrolled intracranial hypertension by intracranial pressure (ICP) monitoring (if applicable).
- Evidence of Wilson's disease, alcoholic hepatitis, biliary obstruction, ischemic hepatitis, severe acute renal tubular necrosis (ATN) due to shock, or any patient with ongoing hypotension.
- Significant gastrointestinal bleeding (coffee grounds per nasogastric tube and/or melena).
- Hemodynamic instability, defined by a mean arterial pressure of <65 mmHg.
- Cardiopulmonary complications such as pulmonary edema, aspiration pneumonia, heart failure.
Show all 11Show fewer
- QT interval of >500msec at baseline EKG.
- Pregnancy.
- History of malignancy that has not been cured or any cancer in remission for less than 1 within the past 5 year. Non-melanoma skin cancers do not preclude participation in the trial.
- Concomitant administration of drugs known to interfere with renal excretion of phenylacetylglutamine or those medications that may induce hyperammonemia such as haloperidol, valproic acid and systemic corticosteroids (prohibited during the study). Alternative ammonia modifying agents such as lactulose and rifaximin are not considered standard of care and are prohibited during the study period.
- Any other health condition that would preclude participation in the study in the judgment of the principal investigator.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
University of Michigan Medical Center
Ann Arbor, Michigan, 48109
Emory University
Atlanta, Georgia, 30322
Medical University of South Carolina
Charleston, South Carolina, 29425
Northwestern University
Chicago, Illinois, 60611
The Ohio State University
Columbus, Ohio, 43210
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
University of Kansas Medical Center
Kansas City, Kansas, 66160
Yale University School of Medicine
New Haven, Connecticut, 06520
Virginia Commonwealth University
Richmond, Virginia, 23298
University of California, San Francisco
San Francisco, California, 94107
University of Washington
Seattle, Washington, 98195
About this study
Official title: 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
This Phase 2a clinical study is designed to provide data on OCR-002 in patients with acute liver failure/acute liver injury (ALF/ALI) in regard to:
- safety and tolerability;
- metabolism of the compound to glutamine and phenylacetylglutamine (PAGN);
- its effect on circulating ammonia levels and neurological function in patients with and without impaired renal function after continuous infusion at different infusion rates.
Read more
Subjects will receive up to 120 hours (5 days) of drug infusion, followed by a 30 day follow-up visit post infusion. It is anticipated that this early safety and tolerability study, with appropriate PK/PD data, will lead to a development program for the use of OCR-002 in the treatment of hyperammonemia either due to ALF or possibly other liver conditions. The hypotheses are:
- Treatment with OCR-002 is safe and tolerable in patients with acute liver failure/acute liver injury due to acetaminophen overdose or drug-induced liver injury, autoimmune hepatitis, viral hepatitis or indeterminate etiologies.
- A dose of 10-20g/24h (0.42-.83g/h) will achieve steady state plasma concentrations within 6-12h with little additional accumulation in the ALI/ALF setting.
- Treatment with OCR-002 will reduce ammonia and improve neurological function in patients with acute liver failure/severe acute liver injury.
Read the detailed description
There is strong experimental and clinical rationale for the use of ammonia-lowering therapies in ALF. Ammonia is normally produced in the gut and transformed by the liver into urea. As the liver fails, ammonia increases in the systemic circulation and enters into the brain. The result of a rapid rise in ammonia or related compounds in the cerebral circulation is hepatic encephalopathy (HE), a reversible neuropsychiatric condition that ranges in severity from mild impairment in attention, to delirium, the development of cerebral edema, coma and death. This is a Phase 2a, multi-center, open-label study, conducted in two cohorts in patients diagnosed with acute liver failure/acute liver injury (ALF/ALI) who meet inclusion/exclusion criteria. This study is designed to provide data on OCR-002 with regards to
- the effect on circulating ammonia levels in patients with acute liver failure with and without impaired renal function at different doses after single and continuous infusion
- safety and dose tolerability as well as
- providing data on the metabolites, glutamine and phenylacetylglutamine in this patient population.
It is anticipated that this early efficacy, safety, tolerability, Pharmacokinetic/Pharmacodynamic (PK/PD) and dose-ranging study will lead to a Phase 3 development program for the use of OCR-002 in the treatment of hyperammonemia due to ALF. No clinical outcome measures will be formally studied because of the small sample size.
- Conditions
- Acute Liver Failure, Acute Liver Injury
- Being tested
- Ornithine Phenylacetate
- Keywords
- ornithine, phenylacetate, acetaminophen toxicity, acute liver failure, hepatitis B, autoimmune hepatitis, drug-induced liver injury
- Medical subject headings
- Liver Failure, Acute, Hepatitis B, Hepatitis, Autoimmune, Chemical and Drug Induced Liver Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ornithine PhenylacetateDrug
Also called OCR-002
Up to 36 patients will be enrolled into 2 groups [~18 with minimal renal dysfunction (Cohort 1) \& ~18 w/ comprised renal function (Cohort 2)] and receive OCR-002 infusion for at least 72 hrs. OCR-002 will be administered in the vein and pharmacokinetics (pk) assessed for all subjects who receive the infusion.
The first 24 enrolled subjects received OCR-002 at 3 ascending dose levels (DLs 1-3) with a maximum target infusion rate equivalent to 10g/24h.
The remaining 12 patients (~6 Cohort 1 \& ~6 Cohort 2) will be enrolled and receive identical quantities of OCR-002 at 20g/24hr continuously for 5 days (Dose Level 4).
| Study group | Role | What they receive |
|---|---|---|
| Ornithine·Phenylacetate | Experimental | Ornithine Phenylacetate is administered intravenously, through a peripheral venous catheter. Each infusion should will be administered over a period of 120 hours. Receives: Drug: Ornithine Phenylacetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
To evaluate the safety and tolerability of OCR-002 in patients with acute liver failure/severe acute liver injury
Measured: 30 Days
Secondary outcomes (4)
Measurement of OCR-002 Plasma Concentration
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
Measured: 24 Hours after last infusion
Change in Ammonia
To evaluate the effect of OCR-002 on ammonia levels in patients with acute liver failure/severe acute liver injury
Measured: Baseline and 72 Hours
Neurological Function Measured by the West Haven Criteria (WHC) for Hepatic Encephalopathy
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.
Measured: 120 hours from start of infusion
Neurological Function Measured by the Orientation Log (O-log)
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.
Measured: 30 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2012 (estimated)
- Study startJun 2012
- Primary completion23 Feb 2017
- Study completion23 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (34)Papers the sponsor has linked to this study.
- Other trials for Acute Liver FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- William Lee
- Sponsor type
- University, hospital or other
- Collaborators
- Medical University of South Carolina, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Ocera Therapeutics
- Responsible party
- Sponsor-investigator, William Lee, University of Texas Southwestern Medical Center
- Investigators
- William M Lee, MD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01548690
- Sponsor's protocol ID
- ALFSG-OCR-002
- Other IDs
- U01DK058369
- Acronym
- STOP-ALF
- Status last verified
- Oct 2018
- First submitted
- 24 Feb 2012
- Last updated
- 30 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: De-identified data for the overall study will be shared once the study is completed.
Publications
Lee WM. Etiologies of acute liver failure. Semin Liver Dis. 2008 May;28(2):142-52. doi: 10.1055/s-2008-1073114.
PubMed 18452114Roberts MS, Angus DC, Bryce CL, Valenta Z, Weissfeld L. Survival after liver transplantation in the United States: a disease-specific analysis of the UNOS database. Liver Transpl. 2004 Jul;10(7):886-97. doi: 10.1002/lt.20137.
PubMed 15237373Stravitz RT, Kramer DJ. Management of acute liver failure. Nat Rev Gastroenterol Hepatol. 2009 Sep;6(9):542-53. doi: 10.1038/nrgastro.2009.127. Epub 2009 Aug 4.
PubMed 19652652Blei AT. Pathogenesis of brain edema in fulminant hepatic failure. Prog Liver Dis. 1995;13:311-30. No abstract available.
PubMed 9224508Jalan R. Pathophysiological basis of therapy of raised intracranial pressure in acute liver failure. Neurochem Int. 2005 Jul;47(1-2):78-83. doi: 10.1016/j.neuint.2005.04.010.
PubMed 15927306Larsen FS, Wendon J. Prevention and management of brain edema in patients with acute liver failure. Liver Transpl. 2008 Oct;14 Suppl 2:S90-6. doi: 10.1002/lt.21643.
PubMed 18825686Clemmesen JO, Larsen FS, Kondrup J, Hansen BA, Ott P. Cerebral herniation in patients with acute liver failure is correlated with arterial ammonia concentration. Hepatology. 1999 Mar;29(3):648-53. doi: 10.1002/hep.510290309.
PubMed 10051463Blei AT, Larsen FS. Pathophysiology of cerebral edema in fulminant hepatic failure. J Hepatol. 1999 Oct;31(4):771-6. doi: 10.1016/s0168-8278(99)80361-4. No abstract available.
PubMed 10551405Bhatia V, Singh R, Acharya SK. Predictive value of arterial ammonia for complications and outcome in acute liver failure. Gut. 2006 Jan;55(1):98-104. doi: 10.1136/gut.2004.061754. Epub 2005 Jul 15.
PubMed 16024550Traber PG, Dal Canto M, Ganger DR, Blei AT. Electron microscopic evaluation of brain edema in rabbits with galactosamine-induced fulminant hepatic failure: ultrastructure and integrity of the blood-brain barrier. Hepatology. 1987 Nov-Dec;7(6):1272-7. doi: 10.1002/hep.1840070616.
PubMed 3679092Cordoba J, Gottstein J, Blei AT. Glutamine, myo-inositol, and organic brain osmolytes after portocaval anastomosis in the rat: implications for ammonia-induced brain edema. Hepatology. 1996 Oct;24(4):919-23. doi: 10.1002/hep.510240427.
PubMed 8855198Rose C, Michalak A, Rao KV, Quack G, Kircheis G, Butterworth RF. L-ornithine-L-aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure. Hepatology. 1999 Sep;30(3):636-40. doi: 10.1002/hep.510300311.
PubMed 10462368Rose C, Michalak A, Pannunzio M, Chatauret N, Rambaldi A, Butterworth RF. Mild hypothermia delays the onset of coma and prevents brain edema and extracellular brain glutamate accumulation in rats with acute liver failure. Hepatology. 2000 Apr;31(4):872-7. doi: 10.1053/he.2000.5923.
PubMed 10733542Jalan R, Wright G, Davies NA, Hodges SJ. L-Ornithine phenylacetate (OP): a novel treatment for hyperammonemia and hepatic encephalopathy. Med Hypotheses. 2007;69(5):1064-9. doi: 10.1016/j.mehy.2006.12.061. Epub 2007 Apr 27.
PubMed 17467190Polson J, Lee WM; American Association for the Study of Liver Disease. AASLD position paper: the management of acute liver failure. Hepatology. 2005 May;41(5):1179-97. doi: 10.1002/hep.20703. No abstract available.
PubMed 15841455
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01548690
- Acronym / sponsor ID
- STOP-ALF / ALFSG-OCR-002
- Conditions
- Acute Liver Failure, Acute Liver Injury
- Keywords
- ornithine, phenylacetate, acetaminophen toxicity, acute liver failure, hepatitis B, autoimmune hepatitis, drug-induced liver injury
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- William LeeUniversity, hospital or other
- Collaborators
- Medical University of South Carolina, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Ocera Therapeutics
- Study start
- Jun 2012
- Primary completion
- 23 Feb 2017 (actual)
- Study completion
- 23 Feb 2017 (actual)
- First posted
- 8 Mar 2012 (estimated)
- Results
- Posted 20 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase 2a clinical study is designed to provide data on OCR-002 in patients with acute liver failure/acute liver injury (ALF/ALI) in regard to:
- safety and tolerability;
- metabolism of the compound to glutamine and phenylacetylglutamine (PAGN);
- its effect on circulating ammonia levels and neurological function in patients with and without impaired renal function after continuous infusion at different infusion rates.
Subjects will receive up to 120 hours (5 days) of drug infusion, followed by a 30 day follow-up visit post infusion. It is anticipated that this early safety and tolerability study, with appropriate PK/PD data, will lead to a development program for the use of OCR-002 in the treatment of hyperammonemia either due to ALF or possibly other liver conditions. The hypotheses are:
- Treatment with OCR-002 is safe and tolerable in patients with acute liver failure/acute liver injury due to acetaminophen overdose or drug-induced liver injury, autoimmune hepatitis, viral hepatitis or indeterminate etiologies.
- A dose of 10-20g/24h (0.42-.83g/h) will achieve steady state plasma concentrations within 6-12h with little additional accumulation in the ALI/ALF setting.
- Treatment with OCR-002 will reduce ammonia and improve neurological function in patients with acute liver failure/severe acute liver injury.
Detailed description
There is strong experimental and clinical rationale for the use of ammonia-lowering therapies in ALF. Ammonia is normally produced in the gut and transformed by the liver into urea. As the liver fails, ammonia increases in the systemic circulation and enters into the brain. The result of a rapid rise in ammonia or related compounds in the cerebral circulation is hepatic encephalopathy (HE), a reversible neuropsychiatric condition that ranges in severity from mild impairment in attention, to delirium, the development of cerebral edema, coma and death. This is a Phase 2a, multi-center, open-label study, conducted in two cohorts in patients diagnosed with acute liver failure/acute liver injury (ALF/ALI) who meet inclusion/exclusion criteria. This study is designed to provide data on OCR-002 with regards to
- the effect on circulating ammonia levels in patients with acute liver failure with and without impaired renal function at different doses after single and continuous infusion
- safety and dose tolerability as well as
- providing data on the metabolites, glutamine and phenylacetylglutamine in this patient population.
It is anticipated that this early efficacy, safety, tolerability, Pharmacokinetic/Pharmacodynamic (PK/PD) and dose-ranging study will lead to a Phase 3 development program for the use of OCR-002 in the treatment of hyperammonemia due to ALF. No clinical outcome measures will be formally studied because of the small sample size.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ornithine·Phenylacetate | Experimental | Drug: Ornithine PhenylacetateOrnithine Phenylacetate is administered intravenously, through a peripheral venous catheter. Each infusion should will be administered over a period of 120 hours. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Men and women, ages 18-65 (have not reached their 66th birthday).
- Acute liver failure, defined as the development of coagulopathy (International normalized ratio [INR] ≥1.5) with encephalopathy in a patient with no prior history of liver disease, with onset of symptoms within 28 days of the inciting event. Patients may have either a history of acetaminophen overdose (defined as >4 g/day within 7 days of presentation) and/or detectable acetaminophen levels in the serum, with a pattern of liver function tests typical for acetaminophen toxicity (bilirubin < 10 mg/dL and alanine aminotransferase (ALT) ≥1000 IU/L), or a diagnosis of hepatitis A, hepatitis B, drug-induced liver injury, autoimmune hepatitis or indeterminate cause based on standard criteria.
- ALI patients may also be enrolled (those meeting the above criteria plus coagulopathy (INR ≥ 2.0) and no evidence of encephalopathy)
- Written informed consent from the patient (ALI) or patient's legally authorized representative or family member if he/she is considered encephalopathic (ALF).
- Ammonia level ≥60 μmol/L at baseline (within 8h prior to T0/initiation of infusion).
Key exclusion criteria (11 listed)
- History of chronic liver disease.
- Signs of overt cerebral herniation, or uncontrolled intracranial hypertension by intracranial pressure (ICP) monitoring (if applicable).
- Evidence of Wilson's disease, alcoholic hepatitis, biliary obstruction, ischemic hepatitis, severe acute renal tubular necrosis (ATN) due to shock, or any patient with ongoing hypotension.
- Significant gastrointestinal bleeding (coffee grounds per nasogastric tube and/or melena).
- Hemodynamic instability, defined by a mean arterial pressure of <65 mmHg.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ornithine PhenylacetateAlso: OCR-002Up to 36 patients will be enrolled into 2 groups [~18 with minimal renal dysfunction (Cohort 1) \& ~18 w/ comprised renal function (Cohort 2)] and receive OCR-002 infusion for at least 72 hrs. OCR-002 will be administered in the vein and pharmacokinetics (pk) assessed for all subjects who receive the infusion. The first 24 enrolled subjects received OCR-002 at 3 ascending dose levels (DLs 1-3) with a maximum target infusion rate equivalent to 10g/24h. The remaining 12 patients (~6 Cohort 1 \& ~6 Cohort 2) will be enrolled and receive identical quantities of OCR-002 at 20g/24hr continuously for 5 days (Dose Level 4). | Drug | Ornithine·Phenylacetate |
Primary outcome
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
Time frame: 30 Days
To evaluate the safety and tolerability of OCR-002 in patients with acute liver failure/severe acute liver injury
4 secondary outcomes
Measurement of OCR-002 Plasma Concentration
Time frame: 24 Hours after last infusion
Change in Ammonia
Time frame: Baseline and 72 Hours
Neurological Function Measured by the West Haven Criteria (WHC) for Hepatic Encephalopathy
Time frame: 120 hours from start of infusion
Neurological Function Measured by the Orientation Log (O-log)
Time frame: 30 Days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18452114Lee WM. Etiologies of acute liver failure. Semin Liver Dis. 2008 May;28(2):142-52. doi: 10.1055/s-2008-1073114.
- Background: PubMed 15237373Roberts MS, Angus DC, Bryce CL, Valenta Z, Weissfeld L. Survival after liver transplantation in the United States: a disease-specific analysis of the UNOS database. Liver Transpl. 2004 Jul;10(7):886-97. doi: 10.1002/lt.20137.
- Background: PubMed 19652652Stravitz RT, Kramer DJ. Management of acute liver failure. Nat Rev Gastroenterol Hepatol. 2009 Sep;6(9):542-53. doi: 10.1038/nrgastro.2009.127. Epub 2009 Aug 4.
- Background: PubMed 9224508Blei AT. Pathogenesis of brain edema in fulminant hepatic failure. Prog Liver Dis. 1995;13:311-30. No abstract available.
- Background: PubMed 15927306Jalan R. Pathophysiological basis of therapy of raised intracranial pressure in acute liver failure. Neurochem Int. 2005 Jul;47(1-2):78-83. doi: 10.1016/j.neuint.2005.04.010.
- Background: PubMed 18825686Larsen FS, Wendon J. Prevention and management of brain edema in patients with acute liver failure. Liver Transpl. 2008 Oct;14 Suppl 2:S90-6. doi: 10.1002/lt.21643.
- Background: PubMed 10051463Clemmesen JO, Larsen FS, Kondrup J, Hansen BA, Ott P. Cerebral herniation in patients with acute liver failure is correlated with arterial ammonia concentration. Hepatology. 1999 Mar;29(3):648-53. doi: 10.1002/hep.510290309.
- Background: PubMed 10551405Blei AT, Larsen FS. Pathophysiology of cerebral edema in fulminant hepatic failure. J Hepatol. 1999 Oct;31(4):771-6. doi: 10.1016/s0168-8278(99)80361-4. No abstract available.
- Background: PubMed 16024550Bhatia V, Singh R, Acharya SK. Predictive value of arterial ammonia for complications and outcome in acute liver failure. Gut. 2006 Jan;55(1):98-104. doi: 10.1136/gut.2004.061754. Epub 2005 Jul 15.
- Background: PubMed 3679092Traber PG, Dal Canto M, Ganger DR, Blei AT. Electron microscopic evaluation of brain edema in rabbits with galactosamine-induced fulminant hepatic failure: ultrastructure and integrity of the blood-brain barrier. Hepatology. 1987 Nov-Dec;7(6):1272-7. doi: 10.1002/hep.1840070616.
- Background: PubMed 8855198Cordoba J, Gottstein J, Blei AT. Glutamine, myo-inositol, and organic brain osmolytes after portocaval anastomosis in the rat: implications for ammonia-induced brain edema. Hepatology. 1996 Oct;24(4):919-23. doi: 10.1002/hep.510240427.
- Background: PubMed 10462368Rose C, Michalak A, Rao KV, Quack G, Kircheis G, Butterworth RF. L-ornithine-L-aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure. Hepatology. 1999 Sep;30(3):636-40. doi: 10.1002/hep.510300311.
- Acute Liver Failure Study WebsiteLink provided by the sponsor.
- Instructional STOP-ALF YouTube VideoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified data for the overall study will be shared once the study is completed.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William M Lee, MD principal investigator
University of Texas Southwestern Medical Center
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ornithine Phenylacetate in people with Acute Liver Failure and Acute Liver Injury, run by William Lee at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 30 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01548690, which also lists 34 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2018.