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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
  Purpose

The purpose of this study is to determine whether albumin administration during cardiac surgery is effective in attenuating the development of inflammation following surgery.


Condition Intervention Phase
Systemic Inflammatory Response Syndrome
Cardiopulmonary Bypass
Drug: 20% Human albumin solution
Drug: Gelofusin
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Time from surgery to intensive care unit discharge [ Time Frame: Hourly ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 232
Study Start Date: December 2008
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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)

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

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00773110

Locations
United Kingdom
Adult Intensive Care Unit, Royal Brompton and Harefield NHS Trust
London, United Kingdom, SW3 6NP
Sponsors and Collaborators
Imperial College London
Investigators
Principal Investigator: Mark J Griffiths Royal Brompton & Harefield NHS Foundation Trust
  More Information

No publications provided

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT00773110     History of Changes
Other Study ID Numbers: CRO888, DHTCA_P09889
Study First Received: October 15, 2008
Last Updated: May 27, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: Research Ethics Committee

Keywords provided by Imperial College London:
hemolysis
systemic inflammatory response syndrome
cardiopulmonary bypass
albumin

Additional relevant MeSH terms:
Syndrome
Systemic Inflammatory Response Syndrome
Disease
Inflammation
Pathologic Processes
Shock
Albunex
Pharmaceutical Solutions
Contrast Media
Diagnostic Uses of Chemicals
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014