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

Phase 2

Completed

• Conditions: Gastrointestinal Bleeding; Cirrhosis
• Interventions: Drug: Ornithine-phenylacetate

• Registration Number: NCT01434108
• Lead Sponsor: Hospital Universitari Vall d'Hebron Research Institute

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-09-12
• Study First Submitted QC: 2011-09-13
• Study First Posted: 2011-09-14
• Study Start: 2011-10
• Status Verified: 2015-03
• Primary Completion: 2015-03
• Study Completion: 2015-03
• Last Update Submitted: 2015-03-19
• Last Update Posted: 2015-03-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ornithine-phenylacetate	Ornithine-phenylacetate	Administration of OP (OCR-002) during 5 days in addition to standard treatment of gastrointestinal bleeding.
Saline iv	Ornithine-phenylacetate	Administration of control infusion (saline infusion) during 5 days in addition to standard treatment of gastrointestinal bleeding.

Primary Outcome Measures

Name	Time	Method
Ammonia plasma concentration umol/L.	6 days	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.

Secondary Outcome Measures

Name	Time	Method
Hepatic encephalopathy	6 days	Hepatic encephalopathy (HE) is a common complication of cirrhosis,characterized by a myriad of neurological manifestations,diverse underlying liver disorders, and a variety of precipitating factors. For evaluated the presence and severity of HE the CHESS, and WEST-HAVEN scales will be performe because are adequate for clinical trials.

Trial Locations

Locations (1)

Hospital Vall Hebron; 🇪🇸 Barcelona, Spain