Study of Albumin to Reduce Inflammation Following Surgery

Cardiopulmonary Bypass Clinical Trial

Official title:

Scavenging Free Haemoglobin Attenuates the Systemic Inflammatory Response Following Surgery

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00773110
• Other study ID #: CRO888
• Secondary ID: DHTCA_P09889
• Status: Terminated
• Phase: Phase 2
• First received: October 15, 2008
• Last updated: May 27, 2014
• Start date: December 2008
• Est. completion date: May 2011

Study information

• Verified date: May 2010
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: National Health ServiceUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 232
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiopulmonary Bypass
• Systemic Inflammatory Response Syndrome

Intervention

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)
• 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)

Locations

Country	Name	City	State
United Kingdom	Adult Intensive Care Unit, Royal Brompton and Harefield NHS Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Imperial College London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time from surgery to intensive care unit discharge		Hourly	No
Secondary	Degree of hemolysis - free hemoglobin and haptoglobin		Prior to and at 0, 2, 6 and 24 hours after CPB	No
Secondary	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	No
Secondary	Biochemical and physiological markers of organ dysfunction		At regular intervals following CPB until intensive care unit discharge	No
Secondary	Haematological markers of the inflammatory response		Prior to and at 0, 2, 6 and 24 hours after CPB	No