Study of Albumin to Reduce Inflammation Following Surgery

This study has been terminated.
(Recruitment under target, Finding)
Sponsor:
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT00773110
First received: October 15, 2008
Last updated: May 27, 2014
Last verified: May 2010

October 15, 2008
May 27, 2014
December 2008
May 2011   (final data collection date for primary outcome measure)
Time from surgery to intensive care unit discharge [ Time Frame: Hourly ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00773110 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Systemic Inflammatory Response Syndrome
  • Cardiopulmonary Bypass
  • 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
  • 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)
  • Experimental: 1 Albumin
    Priming of the cardiopulmonary bypass circuit with 20% human albumin solution prior to surgery
    Intervention: Drug: 20% Human albumin solution
  • Placebo Comparator: 2 Gelofusin
    Priming of the cardiopulmonary bypass circuit with gelofusin prior to surgery
    Intervention: Drug: Gelofusin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
232
May 2011
May 2011   (final data collection date for primary outcome measure)

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
Both
16 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
NCT00773110
CRO888, DHTCA_P09889
Yes
Imperial College London
Imperial College London
Not Provided
Principal Investigator: Mark J Griffiths Royal Brompton & Harefield NHS Foundation Trust
Imperial College London
May 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP