CirrhosisPhase 3InfecirNCT00124228
Albumin Administration in Patients With Cirrhosis and Infections Unrelated to Spontaneous Bacterial Peritonitis
A Phase 3 study testing Human Albumin in people with Cirrhosis, run by Hospital Clinic of Barcelona at 1 site in Spain.
Trial summary
Spontaneous bacterial peritonitis (SBP) present in cirrhotic patients induces severe circulatory dysfunction, which results in renal failure in up to 30% of the patients. Renal failure is an important prognostic marker, representing the major predictive factor of in-hospital mortality. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cirrhosis
- What is being tested?
- Human Albumin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteSpain
- Study dates
- Nov 2004to Oct 2008
- Phase
- Phase 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 18 and 75 years;
- Cirrhosis defined by clinical, analytical or histological criteria;
- Active infection defined by the presence of at least two of the criteria for systemic inflammatory response syndrome (SIRS), necessarily including neutrophilia in the hemogram. In case of a positive culture, the presence of only one of the SIRS criteria is considered sufficient for the infection diagnosis. SIRS is defined by: temperature >38º or <36º C, heart beat >90 beats/min, breath frequency >20 resp/min, white cell count >12000/mm3 or <4000/mm3 or >6% of immature cells.
- Written informed consent.
- Absence of the exclusion criteria described below
Who cannot join
- Use of antibiotics during the week preceding the study, except for prophylaxis of spontaneous bacterial peritonitis;
- Hepatocarcinoma: hepatocarcinoma patients presenting more than 3 nodes > 3 cm, or one node larger than 5 cm, tumoral portal thrombosis or extrahepatic tumor extension;
- Heart insufficiency or advanced chronic obstructive pulmonary disease;
- Digestive bleeding during the week preceding the study;
- Presence of septic shock, defined as: sepsis with hypotension (systolic pressure <90 mm Hg or a decrease >40 mm Hg as compared to the basal pressure), in spite of an adequate liquid reposition, signs of a poor peripheral perfusion or need of vasoactive drugs;
- Plasma creatinine > 3 mg/dL;
- Severe dehydration (defined by a central venous pressure < 3 cm H2O due to severe diarrhea or to a strong response to diuretic treatment) at inclusion in the study; the patients with PVC lower than 3 will receive plasma volume expansion with saline and will be reevaluated within 24 h. If the expansion is able to correct PVC (defined as PVC > 3), the patients will be apt to be included in the study.
- Existence of diseases which can influence the short term survival.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Intravenous Albumin Administration on Renal Function and Survival in Patients With Cirrhosis and Infections Unrelated to Spontaneous Bacterial Peritonitis. A Prospective, Stratified, Randomized and Controlled Study.
Spontaneous bacterial peritonitis (SBP) present in cirrhotic patients induces severe circulatory dysfunction, which results in renal failure in up to 30% of the patients. Renal failure is an important prognostic marker, representing the major predictive factor of in-hospital mortality.
Recent studies have shown that plasma volume expansion with albumin associated with cefotaxime in patients with SBP is more efficient to prevent renal failure than cefotaxime treatment alone. The in-hospital and three-month mortality rates, furthermore, were significantly lower in the group treated with albumin.
Read more
It is not known if other bacterial infections unrelated to SBP represent a risk factor for the development of renal failure among cirrhotic patients. The researcher's group has recently performed a study to evaluate the incidence, characteristics and outcome, of renal failure in patients with cirrhosis and bacterial infections unrelated to SBP associated with the systemic inflammatory response syndrome (Terra, unpublished results). Among a total of 106 patients, 29 (27%) presented renal failure during the course of infection. Renal failure was characterized by intense renal vasoconstriction (intrarenal resistive index of 0.83 +/- 0.09, measured by Doppler ultrasound), reduction of mean arterial pressure and an important activation of endogenous vasoconstriction systems. The three-month survival probability of patients with infection and renal failure was 34 %, much lower than that of patients with infection but not presenting renal failure (87%, p<0.0001). These results suggest that the development of renal failure in patients with cirrhosis and bacterial infections different from SBP, associated with signs of a systemic inflammatory response, is very frequent and results in a very poor prognosis. Taken as a whole, these data strongly indicate the need to consider these patients as candidates for liver transplantation and to plan strategies for its prevention.
The objective of this project, therefore, is to evaluate if the plasma volume expansion with albumin, associated with conventional antibiotic therapy, can prevent the development of renal failure and increase survival rates in cirrhotic patients with bacterial infections unrelated to spontaneous bacterial peritonitis.
Read the detailed description
Recent studies have shown that the administration of cefotaxime (first choice treatment for SBP) associated with plasma volume expansion with albumin in patients with SBP, was more efficient to prevent renal failure than cefotaxime treatment alone (10% vs. 33%, respectively). The in-hospital and three-month mortality rates, furthermore, were significantly lower in the group treated with albumin (10% vs. 29% and 22% vs. 41%, respectively). There was a significant increase in the plasma renin activity in the group treated with cefotaxime alone as compared to the group receiving cefotaxime associated with the expansion with albumin. A direct relationship between plasma renin activity levels and the development of renal failure was also observed.
Based on the previous information the main objective of this study is to evaluate if the plasma volume expansion with albumin associated to conventional antibiotics therapy, can prevent the development of renal failure and increase survival rates in cirrhotic patients with bacterial infections unrelated to spontaneous bacterial peritonitis. If that proves to be the case, albumin should be administered as first choice treatment associated with antibiotics to all the cirrhotic patients with bacterial infection and systemic inflammatory response syndrome.
Other parameters to be investigated include:
- In-hospital mortality.
- Evaluation of the treatment effects over the renal vascular territory, estimated by Doppler ultrasonography of the intrarenal arteries.
- Evaluation of the relationship between the development of renal failure and the activity of endogenous vasoactive systems: plasma renin activity, plasma concentration of aldosterone, noradrenaline, atrial natriuretic factor and nitrites. Evaluation of the relationship between the development of renal failure and the concentration of inflammatory cytokines: tumor necrosis factor-α, interleukin-6, interleukin-1, interleukin-10.
- Evaluation of heart function and its relationship with the development of renal failure.
- Conditions
- Cirrhosis
- Being tested
- Human Albumin
- Keywords
- Cirrhosis, Infection, Sepsis, Renal failure
- Medical subject headings
- Fibrosis, Infections, Sepsis, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human AlbuminDrug
albumin 1.5g/kg body weight the first day of inclusion plus 1g/kg/body weight the 3th day of inclusion.
| Study group | Role | What they receive |
|---|---|---|
| 1 | No intervention | Antibiotic following hospital Protocols according the cause of the infection . |
| 2 | Active comparator | Antibiotic following hospital Protocols according the cause of infection plus albumin Receives: Drug: Human Albumin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Renal failure rate
presence of renal failure at admision or development during hospitalization
Measured: During hospitalization
Renal failure rate
outcome of renal failure 3 months after inclusion in the study
Measured: at 3 month
Secondary outcomes (5)
In-hospital and at 3 month mortality
Measured: During hospitalization and 3-month mortality
Evaluation of the treatment effects over the renal vascular territory
Renal resistence index will be determined at baseline and at the end of treatment
Measured: at the end of antibiotic treatment (infection resolution)
Evaluation of the relationship between the development of renal failure and the activity of endogenous vasoactive systems
Evaluation of vasoactive systems and the development or presence of renal failure. These relationships will be evaluated at baseline, at day 3rd and at the end of antibiotic treatment
Measured: At baseline, at day 3rd and at the end of treatment
Evaluation of the relationship between the development of renal failure and the concentration of inflammatory cytokines
Evaluation of cytokines levels and the development or presence of renal failure. These relationships will be evaluated at baseline, at day 3rd and at the end of antibiotic treatment
Measured: At baseline, at day 3rd and at the end of treatment
Evaluation of heart function and its relationship with the development of renal failure
Evaluation of heart function and the development or presence of renal failure. These relationships will be evaluated at baseline, and at the end of antibiotic treatment
Measured: At baseline and at the end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2005 (estimated)
- Study startNov 2004
- Primary completionOct 2008
- Study completionOct 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CirrhosisStudies of the same condition, open and under way.
- More trials run by Hospital Clinic of BarcelonaThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Clinic of Barcelona
- Sponsor type
- University, hospital or other
- Collaborators
- Fondo de Investigacion Sanitaria
- Investigators
- Pere Ginès, Dr, Principal investigator, Hospital Clinic of Barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00124228
- Sponsor's protocol ID
- FIS05/0273
- Other IDs
- FIS
- Acronym
- Infecir
- Status last verified
- Aug 2009
- First submitted
- 26 Jul 2005
- Last updated
- 27 May 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
Guevara M, Terra C, Nazar A, Sola E, Fernandez J, Pavesi M, Arroyo V, Gines P. Albumin for bacterial infections other than spontaneous bacterial peritonitis in cirrhosis. A randomized, controlled study. J Hepatol. 2012 Oct;57(4):759-65. doi: 10.1016/j.jhep.2012.06.013. Epub 2012 Jun 23.
PubMed 22732511
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Intravenous Albumin Administration on Renal Function and Survival in Patients With Cirrhosis and Infections Unrelated to Spontaneous Bacterial Peritonitis. A Prospective, Stratified, Randomized and Controlled Study.
- ClinicalTrials.gov ID
- NCT00124228
- Acronym / sponsor ID
- Infecir / FIS05/0273
- Conditions
- Cirrhosis
- Keywords
- Cirrhosis, Infection, Sepsis, Renal failure
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- Hospital Clinic of BarcelonaUniversity, hospital or other
- Collaborators
- Fondo de Investigacion Sanitaria
- Study start
- Nov 2004
- Primary completion
- Oct 2008 (actual)
- Study completion
- Oct 2008 (actual)
- First posted
- 27 Jul 2005 (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.
Spontaneous bacterial peritonitis (SBP) present in cirrhotic patients induces severe circulatory dysfunction, which results in renal failure in up to 30% of the patients. Renal failure is an important prognostic marker, representing the major predictive factor of in-hospital mortality.
Recent studies have shown that plasma volume expansion with albumin associated with cefotaxime in patients with SBP is more efficient to prevent renal failure than cefotaxime treatment alone. The in-hospital and three-month mortality rates, furthermore, were significantly lower in the group treated with albumin.
It is not known if other bacterial infections unrelated to SBP represent a risk factor for the development of renal failure among cirrhotic patients. The researcher's group has recently performed a study to evaluate the incidence, characteristics and outcome, of renal failure in patients with cirrhosis and bacterial infections unrelated to SBP associated with the systemic inflammatory response syndrome (Terra, unpublished results). Among a total of 106 patients, 29 (27%) presented renal failure during the course of infection. Renal failure was characterized by intense renal vasoconstriction (intrarenal resistive index of 0.83 +/- 0.09, measured by Doppler ultrasound), reduction of mean arterial pressure and an important activation of endogenous vasoconstriction systems. The three-month survival probability of patients with infection and renal failure was 34 %, much lower than that of patients with infection but not presenting renal failure (87%, p<0.0001). These results suggest that the development of renal failure in patients with cirrhosis and bacterial infections different from SBP, associated with signs of a systemic inflammatory response, is very frequent and results in a very poor prognosis. Taken as a whole, these data strongly indicate the need to consider these patients as candidates for liver transplantation and to plan strategies for its prevention.
The objective of this project, therefore, is to evaluate if the plasma volume expansion with albumin, associated with conventional antibiotic therapy, can prevent the development of renal failure and increase survival rates in cirrhotic patients with bacterial infections unrelated to spontaneous bacterial peritonitis.
Detailed description
Recent studies have shown that the administration of cefotaxime (first choice treatment for SBP) associated with plasma volume expansion with albumin in patients with SBP, was more efficient to prevent renal failure than cefotaxime treatment alone (10% vs. 33%, respectively). The in-hospital and three-month mortality rates, furthermore, were significantly lower in the group treated with albumin (10% vs. 29% and 22% vs. 41%, respectively). There was a significant increase in the plasma renin activity in the group treated with cefotaxime alone as compared to the group receiving cefotaxime associated with the expansion with albumin. A direct relationship between plasma renin activity levels and the development of renal failure was also observed.
Based on the previous information the main objective of this study is to evaluate if the plasma volume expansion with albumin associated to conventional antibiotics therapy, can prevent the development of renal failure and increase survival rates in cirrhotic patients with bacterial infections unrelated to spontaneous bacterial peritonitis. If that proves to be the case, albumin should be administered as first choice treatment associated with antibiotics to all the cirrhotic patients with bacterial infection and systemic inflammatory response syndrome.
Other parameters to be investigated include:
- In-hospital mortality.
- Evaluation of the treatment effects over the renal vascular territory, estimated by Doppler ultrasonography of the intrarenal arteries.
- Evaluation of the relationship between the development of renal failure and the activity of endogenous vasoactive systems: plasma renin activity, plasma concentration of aldosterone, noradrenaline, atrial natriuretic factor and nitrites. Evaluation of the relationship between the development of renal failure and the concentration of inflammatory cytokines: tumor necrosis factor-α, interleukin-6, interleukin-1, interleukin-10.
- Evaluation of heart function and its relationship with the development of renal failure.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | No intervention | –Antibiotic following hospital Protocols according the cause of the infection . |
| 2 | Active comparator | Drug: Human AlbuminAntibiotic following hospital Protocols according the cause of infection plus albumin |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age between 18 and 75 years;
- Cirrhosis defined by clinical, analytical or histological criteria;
- Active infection defined by the presence of at least two of the criteria for systemic inflammatory response syndrome (SIRS), necessarily including neutrophilia in the hemogram. In case of a positive culture, the presence of only one of the SIRS criteria is considered sufficient for the infection diagnosis. SIRS is defined by: temperature >38º or <36º C, heart beat >90 beats/min, breath frequency >20 resp/min, white cell count >12000/mm3 or <4000/mm3 or >6% of immature cells.
- Written informed consent.
- Absence of the exclusion criteria described below
Key exclusion criteria (8 listed)
- Use of antibiotics during the week preceding the study, except for prophylaxis of spontaneous bacterial peritonitis;
- Hepatocarcinoma: hepatocarcinoma patients presenting more than 3 nodes > 3 cm, or one node larger than 5 cm, tumoral portal thrombosis or extrahepatic tumor extension;
- Heart insufficiency or advanced chronic obstructive pulmonary disease;
- Digestive bleeding during the week preceding the study;
- Presence of septic shock, defined as: sepsis with hypotension (systolic pressure <90 mm Hg or a decrease >40 mm Hg as compared to the basal pressure), in spite of an adequate liquid reposition, signs of a poor peripheral perfusion or need of vasoactive drugs;
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 |
|---|---|---|
| Human Albuminalbumin 1.5g/kg body weight the first day of inclusion plus 1g/kg/body weight the 3th day of inclusion. | Drug | 2 |
Primary outcome
Renal failure rate
Time frame: During hospitalization
presence of renal failure at admision or development during hospitalization
Renal failure rate
Time frame: at 3 month
outcome of renal failure 3 months after inclusion in the study
5 secondary outcomes
In-hospital and at 3 month mortality
Time frame: During hospitalization and 3-month mortality
Evaluation of the treatment effects over the renal vascular territory
Time frame: at the end of antibiotic treatment (infection resolution)
Evaluation of the relationship between the development of renal failure and the activity of endogenous vasoactive systems
Time frame: At baseline, at day 3rd and at the end of treatment
Evaluation of the relationship between the development of renal failure and the concentration of inflammatory cytokines
Time frame: At baseline, at day 3rd and at the end of treatment
Evaluation of heart function and its relationship with the development of renal failure
Time frame: At baseline and at the end of treatment
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 27 May 2010.
- Derived from this study: PubMed 22732511Guevara M, Terra C, Nazar A, Sola E, Fernandez J, Pavesi M, Arroyo V, Gines P. Albumin for bacterial infections other than spontaneous bacterial peritonitis in cirrhosis. A randomized, controlled study. J Hepatol. 2012 Oct;57(4):759-65. doi: 10.1016/j.jhep.2012.06.013. Epub 2012 Jun 23.
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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.
Pere Ginès, Dr principal investigator
Hospital Clinic of Barcelona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Human Albumin in people with Cirrhosis, run by Hospital Clinic of Barcelona 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 5 inclusion and 8 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 27 May 2010. 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. 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 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?
Renal failure rate (time frame: During hospitalization). The study lists 2 primary outcomes in all. 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 NCT00124228, which also lists 1 linked publication.
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 27 May 2010.