Gastrointestinal BleedingPhase 2/3NCT01434108
Effects of the Administration of Ornithine Phenylacetate in Patients With Cirrhosis and Upper Gastrointestinal Bleeding
A Phase 2/3 study testing Ornithine-phenylacetate in people with Gastrointestinal Bleeding and Cirrhosis, run by Hospital Universitari Vall d'Hebron Research Institute at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Gastrointestinal Bleeding, Cirrhosis
- What is being tested?
- Ornithine-phenylacetate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteSpain
- Study dates
- Oct 2011to Mar 2015
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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:
Read more
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
- Being tested
- Ornithine-phenylacetate
- Keywords
- cirrhosis, gastrointestinal bleeding
- Medical subject headings
- Gastrointestinal Hemorrhage, Fibrosis
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
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.
| Study group | Role | What they receive |
|---|---|---|
| Ornithine-phenylacetate | Experimental | Administration of OP (OCR-002) during 5 days in addition to standard treatment of gastrointestinal bleeding. Receives: Drug: Ornithine-phenylacetate |
| Saline iv | Placebo comparator | Administration of control infusion (saline infusion) during 5 days in addition to standard treatment of gastrointestinal bleeding. Receives: Drug: Ornithine-phenylacetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 days
Secondary outcomes (1)
Hepatic encephalopathy
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.
Measured: 6 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2011 (estimated)
- Study startOct 2011
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastrointestinal BleedingStudies of the same condition, open and under way.
- More trials run by Hospital Universitari Vall d'Hebron Research InstituteThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joan Genescà, MD, Principal investigator, EASL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01434108
- Sponsor's protocol ID
- OP_GIB
- Other IDs
- 2009-017819-16, 2009
- Status last verified
- Mar 2015
- First submitted
- 12 Sep 2011
- Last updated
- 24 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of the Administration of Ornithine Phenylacetate in Patients With Cirrhosis and Upper Gastrointestinal Bleeding
- ClinicalTrials.gov ID
- NCT01434108
- Acronym / sponsor ID
- OP_GIB
- Conditions
- Gastrointestinal Bleeding, Cirrhosis
- Keywords
- cirrhosis, gastrointestinal bleeding
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Hospital Universitari Vall d'Hebron Research InstituteUniversity, hospital or other
- Study start
- Oct 2011
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 14 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ornithine-phenylacetate | Experimental | Drug: Ornithine-phenylacetateAdministration of OP (OCR-002) during 5 days in addition to standard treatment of gastrointestinal bleeding. |
| Saline iv | Placebo comparator | Drug: Ornithine-phenylacetateAdministration of control infusion (saline infusion) during 5 days in addition to standard treatment of gastrointestinal bleeding. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
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-002Phase 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. | Drug | Ornithine-phenylacetate, Saline iv |
Primary outcome
Ammonia plasma concentration umol/L.
Time frame: 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.
1 secondary outcome
Hepatic encephalopathy
Time frame: 6 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2015.
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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.
Joan Genescà, MD principal investigator
EASL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Ornithine-phenylacetate in people with Gastrointestinal Bleeding and Cirrhosis, run by Hospital Universitari Vall d'Hebron Research Institute at 1 site in Spain.
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 6 inclusion and 10 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 24 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Ammonia plasma concentration umol/L. (time frame: 6 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Mar 2015.