Preoperative Intravenous Iron to Treat Anaemia in Major Surgery (PREVENTT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University College, London
Sponsor:
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01692418
First received: September 14, 2012
Last updated: January 23, 2014
Last verified: January 2014
  Purpose

Anaemia is a common problem in patients undergoing surgery. About half of patients undergoing a major operation have anaemia, often a consequence of the disease requiring surgery. Anaemia causes patients to feel tired and unwell. Anaemia at the time of surgery increases the requirement for blood transfusion (50% if anaemic compared to only 15% without anaemia). Both anaemia and blood transfusions are associated with increased complications from surgery, delayed recovery and prolonged hospital stay. The investigators propose that giving intravenous iron before operation can be used to correct anaemia in these patients. Consequently if patients are not anaemic they are less likely to need blood transfusion. Also patients feel better and their health is improved before their operation they are more likely to tolerate the surgery, recover faster, be less likely to have complications from surgery and return home sooner. This will have benefits to the individual patient and also to the NHS by reducing costs.

Oral Iron tablets are not effective as they take 3-6 months to increase blood levels, the tablets are often not tolerated as cause constipation or stomach pain, overall only 30-50% of people continue taking oral iron. A full treatment dose of intravenous iron can be given in 15 minutes with minimal side effects. The effect is to rapidly increase blood counts in 2-4 weeks. The investigators propose that this treatment can be incorporated to patient preparation pathways for surgery as an outpatient without the need for additional visits to hospital.

Small studies have suggested a benefit of iron therapy in orthopaedic and gynaecological surgery. This study will look at 500 patients undergoing major surgery at 20 hospitals in the UK. The investigators anticipate half of patients treated will have their anaemia corrected before operation. Patients with anaemia will be identified as part of the routine blood tests taken preoperatively and invited to take part in the study. Following informed consent, they will be randomly allocated to receive either intravenous iron or a placebo infusion of saline. Intravenous iron is a dark liquid given continuously into a vein over 15 minutes. To ensure neither doctor nor patient knows which treatment is being given both infusions will be prepared and administered by an unblinded authorised person via a black bag through black tubing. There will be no other changes to the patient's normal treatment.

The main aim of this study is to assess if intravenous iron will reduce the need for blood transfusion in the time period around the operation. Further outcome measures will include; patient-reported quality of life, complications, length of hospital stay, and cost. Outcomes will be assessed both during hospital stay and after the patient has been discharged. The trial will be run through a Clinical Trials Unit with considerable experience in conducting large trials. The team has a large range of experience in anaemia management and assessment of complications, quality of life and the cost of health care.

The main aim of this study is to assess if intravenous iron will reduce the need for blood transfusion in the time period around the operation. Further outcome measures will include; patient-reported quality of life, complications, length of hospital stay, and cost. Outcomes will be assessed both during hospital stay and after the patient has been discharged. The trial will be run through a Clinical Trials Unit with considerable experience in conducting large trials. The team has a large range of experience in anaemia management and assessment of complications, quality of life and the cost of health care.


Condition Intervention Phase
Anaemia
Drug: Ferric carboxymaltose
Drug: Normal saline
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised Double-blind Controlled Phase III Study to Compare the Efficacy and Safety of Intravenous Ferric Carboxymaltose With Placebo in Patients With Anaemia Undergoing Major Open Abdominal Surgery

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Risk of blood transfusion or death [ Time Frame: From randomisation until 30-days following the index operation ] [ Designated as safety issue: Yes ]
    Co-primary outcome

  • Blood transfusion rate (including repeat transfusions) [ Time Frame: From randomisation until 30-days following the index operation ] [ Designated as safety issue: Yes ]
    Co-primary outcome


Secondary Outcome Measures:
  • Change in haemoglobin levels [ Time Frame: From randomisation to (i) day of index operation, (ii) 8-weeks post index operation and (iii) 6 months post index operation ] [ Designated as safety issue: No ]
  • Total number of units of blood or blood products cross matched, total number of packed red cells and any blood products transfused [ Time Frame: From randomisation to 30 days post index operation ] [ Designated as safety issue: Yes ]
  • Post operative morbidity survey (POMS) outcomes (outcomes will be presence of morbidity defined by the domains of the POMS e.g. gastrointestinal, cardiovascular) [ Time Frame: At days 3, 5, 7 and 14 following the index operation ] [ Designated as safety issue: No ]
  • Health-related quality of life: Change in The Multidimensional Fatigue Inventory (MFI) questionnaire total score [ Time Frame: From baseline to the 10 day assessment and at 8 weeks and 6 months post operatively ] [ Designated as safety issue: No ]
  • Health-related quality of life: Change in European Quality of Life: 5 Dimensions-5 Levels (EQ-5D-5L) questionnaire total score [ Time Frame: From baseline to the 10 day assessment and at 8 weeks and six months post operatively ] [ Designated as safety issue: No ]
  • Health-related quality of life: Change in Single Question Outcome Measure (SQOM) [ Designated as safety issue: No ]
  • Health resource utilisation [ Time Frame: Pre-admission, during admission for index operation, 8 weeks post index operation, and 6 months post index operation ] [ Designated as safety issue: No ]
  • Calculated direct, indirect and total costs for the NHS from two perspectives (payer's and societal perspective) [ Designated as safety issue: No ]
  • Cost effectiveness of treatment options using relevant effectiveness parameters [ Designated as safety issue: No ]
  • Any reaction or side effect from trial therapy [ Designated as safety issue: Yes ]
  • Any reaction or side effect from whole blood or blood product, transfusion reaction [ Designated as safety issue: Yes ]
  • Serious Adverse Events (SAEs) and Suspected Unexpected Serious Adverse Reactions (SUSARs) [ Designated as safety issue: Yes ]
  • Length of hospital stay [ Designated as safety issue: No ]
  • Mortality [ Time Frame: 8 weeks and 6 months post-operatively ] [ Designated as safety issue: No ]
  • Readmission [ Time Frame: Within 8 weeks and within 6 months of the index operation ] [ Designated as safety issue: No ]
  • Blood transfusion [ Time Frame: From randomisation to 8 weeks and 6 months post-operatively ] [ Designated as safety issue: Yes ]
  • Change in e-GFR [ Designated as safety issue: No ]

Estimated Enrollment: 500
Study Start Date: January 2014
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ferric carboxymaltose
1000mg of ferric carboxymaltose will be administered as an i.v. infusion (100ml normal saline) over a minimum of 15 minutes
Drug: Ferric carboxymaltose
1000mg of ferric carboxymaltose will be administered as an i.v. infusion (100ml normal saline)
Other Name: Ferinject
Drug: Normal saline
Normal saline will be administered as an i.v. infusion (100ml normal saline)
Placebo Comparator: Placebo
Normal saline will be administered as an i.v. infusion (100ml normal saline) over a minimum of 15 minutes
Drug: Normal saline
Normal saline will be administered as an i.v. infusion (100ml normal saline)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. At least 18 years of age and signed written informed consent.
  2. Patients undergoing elective major open abdominal surgery.

    • The Indication for operation may be for benign or malignant disease.
    • Major Surgery is defined as an operation of anticipated duration more than one hour where all or part of an abdominal organ is to be removed (hepatectomy, pancreatectomy procedure, gastrectomy, oesophagectomy, colectomy (total/partial), nephrectomy, cystectomy, hysterectomy).
  3. Screening haemoglobin (Hb) greater than or equal to 90 g/L (9.0 g/dL) but below or equal to 120 g/L (12.0 g/dL) within four weeks of randomisation.
  4. Randomisation and administration of study infusion a minimum of 10 days and maximum 42 days before planned operation.
  5. Negative pregnancy test for women of childbearing potential (within last 7 days), and agree to use effective form of contraception until 6 weeks post treatment.
  6. Laboratory data used for determination of eligibility at the baseline visit must not be older than four weeks.

Exclusion Criteria:

  1. Patients undergoing laparoscopic surgery.
  2. Body weight under 50kg.
  3. Known history of acquired iron overload, or family history of haemochromatosis or thalassemia or TSAT > 50%.
  4. Known reason for anaemia (e.g. B12 or folate deficiency or haemoglobinopathy).
  5. Known hypersensitivity to ferric carboxymaltose (Ferinject®) or its excipients.
  6. Temperature > 37.5 degrees celsius or patient on non-prophylactic antibiotics
  7. Chronic liver disease and/or screening alanine transaminase (ALT) or aspartate transaminase (AST) above three times the upper limit of the normal range.
  8. Received erythropoietin, i.v. iron therapy or blood transfusion in the previous 12 weeks.
  9. Immunosuppressive therapy (for organ transplantation) or renal dialysis (current or planned within the next 12 months).
  10. Patients with severe asthma or severe allergy.
  11. Unfit for elective surgery.
  12. Pregnancy or lactation.
  13. Inability to fully comprehend and/or perform study procedures in the investigator's opinion.
  14. Patient involvement in another IMP trial within the previous 4 weeks, prior to randomisation. Involvement in another IMP trial, following randomisation, that may impact on the results of the PREVENTT trial.
  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: NCT01692418

Contacts
Contact: Toby Richards, MD FRCS toby.richards@ucl.ac.uk

Locations
United Kingdom
Dorset County Hospital Recruiting
Dorchester, United Kingdom
Contact: Matthew Hough         
Principal Investigator: Matthew Hough         
Hillingdon Hospital Recruiting
Hillingdon, United Kingdom
Contact: Cheryl Messer         
Principal Investigator: Cheryl Messer         
Royal Free Hospital Recruiting
London, United Kingdom
Contact: Susan Mallett         
Principal Investigator: Susan Mallett         
University College London Recruiting
London, United Kingdom, WC1E 6AU
Contact: James Crosbie         
Principal Investigator: James Crosbie         
Maidstone Hospital Recruiting
Maidstone, United Kingdom
Contact: Andrew Taylor         
Principal Investigator: Andrew Taylor         
Northern General Hospital Recruiting
Sheffield, United Kingdom
Contact: Sumayer Sanghera         
Principal Investigator: Sumayer Sanghera         
Southampton General Hospital Recruiting
Southampton, United Kingdom, SO16 6YD
Contact: Mark Edwards         
Principal Investigator: Mark Edwards         
Royal Cornwall Hospital Recruiting
Truro, United Kingdom
Contact: Catherine Ralph         
Principal Investigator: Catherine Ralph         
York Hospital Recruiting
York, United Kingdom
Contact: Jonathan Wilson         
Principal Investigator: Jonathan Wilson         
Sponsors and Collaborators
University College, London
Investigators
Principal Investigator: Toby Richards, MD FRCS University College, London
  More Information

Additional Information:
No publications provided

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01692418     History of Changes
Other Study ID Numbers: 12/0246, 2012-002786-35, 10/104/06, 12/EE/0445, ISRCTN67322816
Study First Received: September 14, 2012
Last Updated: January 23, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University College, London:
Anaemia
Blood transfusion
Surgery
Iron
Ferric carboxymaltose

Additional relevant MeSH terms:
Anemia
Hematologic Diseases
Ferric Compounds
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014