Effects of the Administration of Ornithine Phenylacetate in Patients With Cirrhosis and Upper Gastrointestinal Bleeding

NCT01434108 | Completed Phase 2

• 2 other identifiers: OP_GIB2009-017819-16
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastrointestinal Bleeding; Cirrhosis

Keywords

cirrhosis, gastrointestinal bleeding

Outcome Measures

Primary Outcomes (1)

• Ammonia plasma concentration umol/L.

  Venous plasma ammonia will be assessed within 60 minutes of extraction in samples withdrawn every 12 hours during the first 48 hours and once a day during the second 72 hours. The concentration of ammonia will be used to decide: a)dose escalating in the initial phase (first 48 hours) of part A and b)discontinuation of treatment in the second phase (second 72 hours) of part B. Blood samples will be processed immediately after being withdrawn to separate plasma under cold conditions. Ammonia will be measured enzymatically in a Cobas Integra analyzer.

  6 days

Secondary Outcomes (1)

• Hepatic encephalopathy

  6 days

Study Arms (2)

Ornithine-phenylacetate

EXPERIMENTAL

Administration of OP (OCR-002) during 5 days in addition to standard treatment of gastrointestinal bleeding.

Drug: Ornithine-phenylacetate

Saline iv

PLACEBO COMPARATOR

Administration of control infusion (saline infusion) during 5 days in addition to standard treatment of gastrointestinal bleeding.

Drug: Ornithine-phenylacetate

Interventions

Ornithine-phenylacetate DRUG

Phase A: Open-label scalating dose of OP. Treatment will be initiated at 1/3 of the final dose and will be scalated every 12 hours up to the full dose, except if there are problems of tolerance. Duration of the infusion 5 days. Phase B: Comparative study of experimental drug vs placebo for 5 days OP (OCR-002) at a dose of 10 g diluted in 150 ml of water for injection administered as a continuous i.v. infusion for 24 hours (8.3 ml/h)during 5 days.

Also known as: OCR-002

Ornithine-phenylacetate; Saline iv

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Hospital Universitari Vall d'Hebron Research Institute: lead

Study Sites (1)

Hospital Vall Hebron

Barcelona, Barcelona, 08035, Spain

Location

MeSH Terms

Conditions

Gastrointestinal Hemorrhage; Fibrosis

Interventions

ornithine phenylacetate

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Joan Genescà, MD

  EASL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2011
• First Posted: September 14, 2011
• Study Start: October 1, 2011
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: March 24, 2015

Record last verified: 2015-03

Locations

ES (1)