Clinical trial NCT01434108: Effects of the Administration of Ornithine Phenylacetate in Patients With Cirrhosis and Upper Gastrointestinal Bleeding
Official title: Effects of the Administration of Ornithine Phenylacetate in Patients With Cirrhosis and Upper Gastrointestinal Bleeding
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Gastrointestinal Bleeding
Cirrhosis
Keywords: cirrhosis, gastrointestinal bleeding
Lead sponsor: Hospital Universitari Vall d'Hebron Research Institute
Sponsor class: OTHER
First posted: 2011-09-14
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main objective is to evaluate the effectiveness of the experimental drug to reduce plasma ammonia concentration at a dose that is safe and well tolerated. Ammonia usually rises significantly in the hours after gastrointestinal bleeding in patients with cirrhosis of the liver. This increase in the concentration of ammonia facilitates the development of hepatic encephalopathy.

The study will be divided in two parts:

Part A: Open-label, dose-escalating, single cohort study. The goal of this phase is to confirm the tolerance and safety of the dose of OP that is being proposed for the study according to the results of phase I and phase II studies in healthy subjects and stable outpatients with cirrhosis.

Part B: Multi-center (2 University Hospitals), double-blind, randomized, parallel-group trial. Assignment of treatment will be done according to a list (one at each study site) of random numbers in blocks that will be concealed until the end of the study. The control group will be assigned to placebo on a 1:1 ratio. The placebo and treatment will be masked.


Eligibility criteria: Inclusion criteria

* Cirrhosis of the liver; diagnosed by clinical, laboratory or radiological findings.
* Upper gastrointestinal bleeding, as judged by clinical signs (hematemesis, melena, anemia) combined with endoscopic data.
* Bleeding that has been active within 24 hours prior to inclusion; signs of activity are defined by the presence of blood in the gastrointestinal tract and symptoms attributable to bleeding (hypotension, tachycardia, etc.).
* Age between 18 and 75 years.
* Informed consent by the patient. In case of inability to provide informed consent due to impaired mental status secondary to hepatic encephalopathy the informed consent should be provided by the next of kin and should be confirmed by the patient when he/she recovers from hepatic encephalopathy.
* Absence of exclusion criteria.

Exclusion criteria

* Terminal illness (e.g. advanced hepatocellular carcinoma).
* Need for mechanical ventilation.
* Renal impairment, defined by a creatinine \> 1.5 mg/dl or need of hemodialysis.
* Pregnant or breast-feeding. Pre-menopausal women capable of bearing children should be following a reliable method of birth control and should have a negative result in a pregnancy test prior to inclusion.
* Known or suspected hypersensitivity or allergic reaction to ornithine or phenylacetate.
* Use of medications known to interfere with the clearance of either ornithine and/or phenylacetate, such as antibiotics of the penicillin group and probenicid.
* Use of medications that may induce hyperammonemia; such as haloperidol, valproic acid, and systemic corticosteroids.
* History or known infection with human immunodeficiency virus (HIV).
* Neurological comorbidities that impair mental status and do not allow to adequately assess the presence or outcome of hepatic encephalopathy.
* The presence in the electrocardiogram of a QTcF \>500 msec

Primary outcomes:
measure: Ammonia plasma concentration umol/L.
timeFrame: 6 days
Secondary outcomes:
measure: Hepatic encephalopathy
timeFrame: 6 days
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Vall Hebron
Study officials:
affiliation: EASL
name: Joan Genescà, MD
role: PRINCIPAL_INVESTIGATOR
References: