Study of Albumin to Reduce Inflammation 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.
Systemic Inflammatory Response Syndrome
Drug: 20% Human albumin solution
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Scavenging Free Haemoglobin Attenuates the Systemic Inflammatory Response Following Surgery|
- Time from surgery to intensive care unit discharge [ Time Frame: Hourly ] [ Designated as safety issue: No ]
- Degree of hemolysis - free hemoglobin and haptoglobin [ Time Frame: Prior to and at 0, 2, 6 and 24 hours after CPB ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Biochemical and physiological markers of organ dysfunction [ Time Frame: At regular intervals following CPB until intensive care unit discharge ] [ Designated as safety issue: No ]
- Haematological markers of the inflammatory response [ Time Frame: Prior to and at 0, 2, 6 and 24 hours after CPB ] [ Designated as safety issue: No ]
|Study Start Date:||December 2008|
|Study Completion Date:||May 2011|
|Primary Completion Date:||May 2011 (Final data collection date for primary outcome measure)|
Experimental: 1 Albumin
Priming of the cardiopulmonary bypass circuit with 20% human albumin solution prior to surgery
Drug: 20% Human albumin solution
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)
Other Name: Zenalb injection
Placebo Comparator: 2 Gelofusin
Priming of the cardiopulmonary bypass circuit with gelofusin prior to surgery
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)
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00773110
|Adult Intensive Care Unit, Royal Brompton and Harefield NHS Trust|
|London, United Kingdom, SW3 6NP|
|Principal Investigator:||Mark J Griffiths||Royal Brompton & Harefield NHS Foundation Trust|