Study of Albumin to Reduce Inflammation Following Surgery

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.

Study Overview

• Status: Terminated
• Conditions: Systemic Inflammatory Response Syndrome; Cardiopulmonary Bypass
• Intervention / Treatment: Drug: 20% Human albumin solution; Drug: Gelofusin

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 Type: Interventional
• Enrollment (Actual): 232
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SW3 6NP
    • Adult Intensive Care Unit, Royal Brompton and Harefield NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: Zenalb injection
PLACEBO_COMPARATOR: 2 Gelofusin; Priming of the cardiopulmonary bypass circuit with gelofusin prior to surgery	Drug: Gelofusin; 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time from surgery to intensive care unit discharge	Hourly

Secondary Outcome Measures

Outcome Measure	Time Frame
Degree of hemolysis - free hemoglobin and haptoglobin	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	At regular intervals following CPB until intensive care unit discharge
Biochemical and physiological markers of organ dysfunction	At regular intervals following CPB until intensive care unit discharge
Haematological markers of the inflammatory response	Prior to and at 0, 2, 6 and 24 hours after CPB

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Mark J Griffiths, Royal Brompton & Harefield NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (ACTUAL): May 1, 2011
• Study Completion (ACTUAL): May 1, 2011

Study Registration Dates

• First Submitted: October 15, 2008
• First Submitted That Met QC Criteria: October 15, 2008
• First Posted (ESTIMATE): October 16, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): May 28, 2014
• Last Update Submitted That Met QC Criteria: May 27, 2014
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: albumin; cardiopulmonary bypass; systemic inflammatory response syndrome; hemolysis
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Shock; Systemic Inflammatory Response Syndrome
• Other Study ID Numbers: CRO888; DHTCA_P09889