Systemic Inflammatory Response SyndromePhase 2NCT00773110
Study of Albumin to Reduce Inflammation Following Surgery
A Phase 2 study testing 20% Human albumin solution and Gelofusin in people with Systemic Inflammatory Response Syndrome and Cardiopulmonary Bypass, run by Imperial College London at 1 site in United Kingdom.
Trial summary
The purpose of this study is to determine whether albumin administration during cardiac surgery is effective in attenuating the development of inflammation following surgery. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Systemic Inflammatory Response Syndrome, Cardiopulmonary Bypass
- What is being tested?
- 20% Human albumin solution and Gelofusin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 232 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Dec 2008to May 2011
- Phase
- Phase 2
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- All patients over sixteen years of age undergoing surgery that requires cardiopulmonary bypass who provide informed written consent
Who cannot join
- Lack of informed consent
- Pregnancy
- Cyanotic congenital heart disease (due to high haemoglobin levels and increased haemolysis)
- Patients undergoing other extracorporeal interventions (ventricular assist devices, extracorporeal membrane oxygenators, pre-admission dialysis)
- Patients with congenital haemoglobinopathies (e.g. thalassaemia, cryoglobinuria, etc)
- Patients with disorders of iron metabolism (e.g. haemochromatosis)
Show all 10Show fewer
- Religious objections to transfusion of a plasma-derived product
- Patients with known blood borne infection
- Patients with known hypersensitivity to gelofusine or human albumin solution
- Patients with an additive EUROSCORE of 10 or more
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Adult Intensive Care Unit, Royal Brompton and Harefield NHS Trust
London, London, SW3 6NP
About this study
Official title: Scavenging Free Haemoglobin Attenuates the Systemic Inflammatory Response Following Surgery
The purpose of this study is to determine whether albumin administration during cardiac surgery is effective in attenuating the development of inflammation following surgery.
Read the detailed description
The host response to infection and other forms of tissue injury has been termed the systemic inflammatory response syndrome (SIRS). SIRS is seen in association with a wide variety of non-infective insults, including major trauma and surgical procedures, including those necessitating cardiopulmonary bypass (CPB). In this population the incidence of SIRS is high, afflicting up to 70% of patients. This may be manifest from an increased vasopressor requirement, to refractory hypotension, and multiple organ dysfunction syndrome (MODS) with liver, renal, myocardial, and neurological problems. MODS is associated with significant mortality rates of around 30-45%. Survivors require prolonged and costly intensive care, thereby representing a considerable burden for the healthcare services. Survivors often suffer considerable morbidity and have significantly impaired health related quality of life.
Despite intense investigations of anti-inflammatory therapies in SIRS and its sequelae, the case of patients is largely supportive whilst underlying triggers (such as infection) for the process are treated. Indeed, the only therapy drotrecogin alfa (activated) demonstrated to reduced mortality in a randomised study has only been investigated in patients with the most severe SIRS consequent of infection (i.e. severe sepsis) and is contra-indicated in those who have just undergone surgery.
Haemolysis is a common feature of surgery requiring CPB and may potentiate the development of SIRS and organ injury through the release of heme/iron. Furthermore, haemolysis during CPB may lead to the depletion of important mechanisms which scavenge free heme/hemoglobin from the circulation. Albumin, the most abundant plasma protein, has specific and non-specific heme and iron binding sites which are used under circumstances in which standard scavengers are overwhelmed. However, albumin is also depleted following CPB. It is therefore hypothesised that by priming the CPB circuit with albumin the heme/iron scavenging capability of the plasma will be maintained following surgery and that the systemic inflammatory response will be attenuated.
- Being tested
- 20% Human albumin solution, Gelofusin
- Keywords
- hemolysis, systemic inflammatory response syndrome, cardiopulmonary bypass, albumin
- Medical subject headings
- Systemic Inflammatory Response Syndrome, Hemolysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
20% Human albumin solutionDrug
Also called Zenalb injection
Priming of the cardiopulmonary bypass circuit with Hartmann's solution (1000 mL), 20% Human serum albumin(300 mL), 0.9% sodium chloride solution (200 mL) and heparin (10,000 IU)
GelofusinDrug
Priming of the cardiopulmonary bypass circuit with Hartmann's solution (1000 mL), Gelofusine (300 mL, 4% succinylated gelatin, a synthetic colloid) and heparin (10,000 IU)
| Study group | Role | What they receive |
|---|---|---|
| 1 Albumin | Experimental | Priming of the cardiopulmonary bypass circuit with 20% human albumin solution prior to surgery Receives: Drug: 20% Human albumin solution |
| 2 Gelofusin | Placebo comparator | Priming of the cardiopulmonary bypass circuit with gelofusin prior to surgery Receives: Drug: Gelofusin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time from surgery to intensive care unit discharge
Measured: Hourly
Secondary outcomes (4)
Degree of hemolysis - free hemoglobin and haptoglobin
Measured: Prior to and at 0, 2, 6 and 24 hours after CPB
Haematological and physiological markers of the inflammatory response - Temperature, pulse rate, respiratory rate, white cell count and C-reactive protein
Measured: At regular intervals following CPB until intensive care unit discharge
Biochemical and physiological markers of organ dysfunction
Measured: At regular intervals following CPB until intensive care unit discharge
Haematological markers of the inflammatory response
Measured: Prior to and at 0, 2, 6 and 24 hours after CPB
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2008 (estimated)
- Study startDec 2008
- Primary completionMay 2011
- Study completionMay 2011
Why it stopped: Recruitment under target, Finding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Inflammatory Response SyndromeStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 232 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark J Griffiths, Principal investigator, Royal Brompton & Harefield NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00773110
- Sponsor's protocol ID
- CRO888
- Other IDs
- DHTCA_P09889
- Status last verified
- May 2010
- First submitted
- 15 Oct 2008
- Last updated
- 28 May 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Scavenging Free Haemoglobin Attenuates the Systemic Inflammatory Response Following Surgery
- ClinicalTrials.gov ID
- NCT00773110
- Acronym / sponsor ID
- CRO888
- Keywords
- hemolysis, systemic inflammatory response syndrome, cardiopulmonary bypass, albumin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment under target, Finding
- Enrolment
- 232 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- Dec 2008
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 16 Oct 2008 (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 purpose of this study is to determine whether albumin administration during cardiac surgery is effective in attenuating the development of inflammation following surgery.
Detailed description
The host response to infection and other forms of tissue injury has been termed the systemic inflammatory response syndrome (SIRS). SIRS is seen in association with a wide variety of non-infective insults, including major trauma and surgical procedures, including those necessitating cardiopulmonary bypass (CPB). In this population the incidence of SIRS is high, afflicting up to 70% of patients. This may be manifest from an increased vasopressor requirement, to refractory hypotension, and multiple organ dysfunction syndrome (MODS) with liver, renal, myocardial, and neurological problems. MODS is associated with significant mortality rates of around 30-45%. Survivors require prolonged and costly intensive care, thereby representing a considerable burden for the healthcare services. Survivors often suffer considerable morbidity and have significantly impaired health related quality of life.
Despite intense investigations of anti-inflammatory therapies in SIRS and its sequelae, the case of patients is largely supportive whilst underlying triggers (such as infection) for the process are treated. Indeed, the only therapy drotrecogin alfa (activated) demonstrated to reduced mortality in a randomised study has only been investigated in patients with the most severe SIRS consequent of infection (i.e. severe sepsis) and is contra-indicated in those who have just undergone surgery.
Haemolysis is a common feature of surgery requiring CPB and may potentiate the development of SIRS and organ injury through the release of heme/iron. Furthermore, haemolysis during CPB may lead to the depletion of important mechanisms which scavenge free heme/hemoglobin from the circulation. Albumin, the most abundant plasma protein, has specific and non-specific heme and iron binding sites which are used under circumstances in which standard scavengers are overwhelmed. However, albumin is also depleted following CPB. It is therefore hypothesised that by priming the CPB circuit with albumin the heme/iron scavenging capability of the plasma will be maintained following surgery and that the systemic inflammatory response will be attenuated.
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 |
|---|---|---|
| 1 Albumin | Experimental | Drug: 20% Human albumin solutionPriming of the cardiopulmonary bypass circuit with 20% human albumin solution prior to surgery |
| 2 Gelofusin | Placebo comparator | Drug: GelofusinPriming of the cardiopulmonary bypass circuit with gelofusin prior to surgery |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- All patients over sixteen years of age undergoing surgery that requires cardiopulmonary bypass who provide informed written consent
Key exclusion criteria (10 listed)
- Lack of informed consent
- Pregnancy
- Cyanotic congenital heart disease (due to high haemoglobin levels and increased haemolysis)
- Patients undergoing other extracorporeal interventions (ventricular assist devices, extracorporeal membrane oxygenators, pre-admission dialysis)
- Patients with congenital haemoglobinopathies (e.g. thalassaemia, cryoglobinuria, etc)
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 |
|---|---|---|
| 20% Human albumin solutionAlso: Zenalb injectionPriming of the cardiopulmonary bypass circuit with Hartmann's solution (1000 mL), 20% Human serum albumin(300 mL), 0.9% sodium chloride solution (200 mL) and heparin (10,000 IU) | Drug | 1 Albumin |
| GelofusinPriming of the cardiopulmonary bypass circuit with Hartmann's solution (1000 mL), Gelofusine (300 mL, 4% succinylated gelatin, a synthetic colloid) and heparin (10,000 IU) | Drug | 2 Gelofusin |
Primary outcome
Time from surgery to intensive care unit discharge
Time frame: Hourly
4 secondary outcomes
Degree of hemolysis - free hemoglobin and haptoglobin
Time frame: Prior to and at 0, 2, 6 and 24 hours after CPB
Haematological and physiological markers of the inflammatory response - Temperature, pulse rate, respiratory rate, white cell count and C-reactive protein
Time frame: At regular intervals following CPB until intensive care unit discharge
Biochemical and physiological markers of organ dysfunction
Time frame: At regular intervals following CPB until intensive care unit discharge
Haematological markers of the inflammatory response
Time frame: Prior to and at 0, 2, 6 and 24 hours after CPB
Results and safety
The study was stopped early (reason given: Recruitment under target, Finding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2014.
Related trials for Systemic Inflammatory Response Syndrome
Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
RecruitingPhase 4
A Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients
Infection, Sepsis
Not yet recruiting
Double Plasma Separation and Adsorption in Acute-on-Chronic Liver Failure (DPMAS-ACLF Trial)
Acute-on-Chronic Liver Failure (ACLF)
Active, not recruitingPhase 4
Thymosin Alpha 1 and IgM Levels in Sepsis
Sepsis, Septic Shock
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.
Mark J Griffiths principal investigator
Royal Brompton & Harefield NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 20% Human albumin solution and Gelofusin in people with Systemic Inflammatory Response Syndrome and Cardiopulmonary Bypass, run by Imperial College London at 1 site in United Kingdom.
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 1 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: stopped early, as of the sponsor's last update on 28 May 2014. 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 United Kingdom. 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 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.
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 was stopped early (reason given: Recruitment under target, Finding). Results are not available in the source record.
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?
Time from surgery to intensive care unit discharge (time frame: Hourly). 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 28 May 2014.