Clinical trial NCT00773110: Study of Albumin to Reduce Inflammation Following Surgery
Official title: Scavenging Free Haemoglobin Attenuates the Systemic Inflammatory Response Following Surgery
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Systemic Inflammatory Response Syndrome
Cardiopulmonary Bypass
Keywords: hemolysis
systemic inflammatory response syndrome
cardiopulmonary bypass
albumin
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2008-10-16
Enrollment: 232
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* All patients over sixteen years of age undergoing surgery that requires cardiopulmonary bypass who provide informed written consent

Exclusion Criteria:

* 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)
* 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

Primary outcomes:
measure: Time from surgery to intensive care unit discharge
timeFrame: Hourly
Secondary outcomes:
measure: Degree of hemolysis - free hemoglobin and haptoglobin
timeFrame: Prior to and at 0, 2, 6 and 24 hours after CPB
measure: Haematological and physiological markers of the inflammatory response - Temperature, pulse rate, respiratory rate, white cell count and C-reactive protein
timeFrame: At regular intervals following CPB until intensive care unit discharge
measure: Biochemical and physiological markers of organ dysfunction
timeFrame: At regular intervals following CPB until intensive care unit discharge
measure: Haematological markers of the inflammatory response
timeFrame: Prior to and at 0, 2, 6 and 24 hours after CPB
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Adult Intensive Care Unit, Royal Brompton and Harefield NHS Trust
Study officials:
affiliation: Royal Brompton & Harefield NHS Foundation Trust
name: Mark J Griffiths
role: PRINCIPAL_INVESTIGATOR
References: