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

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ClinicalTrials.gov Identifier: NCT01692418
Recruitment Status : Recruiting
First Posted : September 25, 2012
Last Update Posted : October 30, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:

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 or disease Intervention/treatment Phase
Anaemia Drug: Ferric carboxymaltose Drug: Normal saline Phase 3

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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
Study Start Date : January 2014
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : August 2019

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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)


Outcome Measures

Primary Outcome Measures :
  1. Risk of blood transfusion or death [ Time Frame: From randomisation until 30-days following the index operation ]
    Co-primary outcome

  2. Blood transfusion rate (including repeat transfusions) [ Time Frame: From randomisation until 30-days following the index operation ]
    Co-primary outcome


Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. Health-related quality of life: Change in Single Question Outcome Measure (SQOM)
  7. Health resource utilisation [ Time Frame: Pre-admission, during admission for index operation, 8 weeks post index operation, and 6 months post index operation ]
  8. Calculated direct, indirect and total costs for the NHS from two perspectives (payer's and societal perspective)
  9. Cost effectiveness of treatment options using relevant effectiveness parameters
  10. Any reaction or side effect from trial therapy
  11. Any reaction or side effect from whole blood or blood product, transfusion reaction
  12. Serious Adverse Events (SAEs) and Suspected Unexpected Serious Adverse Reactions (SUSARs)
  13. Length of hospital stay
  14. Mortality [ Time Frame: 8 weeks and 6 months post-operatively ]
  15. Readmission [ Time Frame: Within 8 weeks and within 6 months of the index operation ]
  16. Blood transfusion [ Time Frame: From randomisation to 8 weeks and 6 months post-operatively ]
  17. Change in e-GFR

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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.
  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) in women or 130 g/L (13.0 g/dL) in men 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. untreated 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. Known chronic liver disease
  8. If clinically indicated for the patient to have LFT's as part of pre-assessment for surgery and this screening alanine transaminase (ALT) or aspartate transaminase (AST) is above three times the upper limit of the normal range.
  9. Received erythropoietin or i.v. iron therapy in the previous 12 weeks.
  10. Immunosuppressive therapy (for organ transplantation) or renal dialysis (current or planned within the next 12 months).
  11. Patients with severe asthma or severe allergy (requiring hospitalisation within the last 12 months).
  12. Unfit for elective surgery.
  13. Pregnancy or lactation.
  14. Inability to fully comprehend and/or perform study procedures in the investigator's opinion.
  15. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01692418


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

Locations
United Kingdom
Basildon University Hospital Active, not recruiting
Basildon, United Kingdom
Blackpool Teaching Hospitals Recruiting
Blackpool, United Kingdom
Principal Investigator: Jason Cupitt         
Southmead Hospital Recruiting
Bristol, United Kingdom
Principal Investigator: Salah Albuheissi         
Broomfield Hospital Recruiting
Broomfield, United Kingdom
Principal Investigator: Toby Hammond         
Countess of Chester Hospital Active, not recruiting
Chester, United Kingdom
Russells Hall Hospital Recruiting
Dudley, United Kingdom
Principal Investigator: Stephen Jenkins         
Royal Infirmary of Edinburgh Recruiting
Edinburgh, United Kingdom
Principal Investigator: Ewen Harrison         
Queen Elizabeth Hospital Active, not recruiting
Gateshead, United Kingdom
Hereford County Hospital Recruiting
Hereford, United Kingdom
Principal Investigator: Lisa Penny         
Hillingdon Hospital Recruiting
Hillingdon, United Kingdom
Contact: Cheryl Messer         
Principal Investigator: Cheryl Messer         
St James's Hospital Recruiting
Leeds, United Kingdom
Principal Investigator: Alwyn Kotze         
Aintree University Hospital Recruiting
Liverpool, United Kingdom
Principal Investigator: Balsam Altemimi         
Liverpool Women's Hospital Recruiting
Liverpool, United Kingdom
Principal Investigator: Helen McNamara         
University College London Recruiting
London, United Kingdom, WC1E 6AU
Principal Investigator: Khaled Dawas         
Guy's and St Thomas' Hospital Recruiting
London, United Kingdom
Principal Investigator: Jugdeep Dhesi         
Imperial College Hospital Recruiting
London, United Kingdom
Principal Investigator: Asela Dharmadasa         
King's College Hospital Recruiting
London, United Kingdom
Principal Investigator: Tim Hughes         
Royal Marsden Recruiting
London, United Kingdom
Principal Investigator: Ravishankar Raobaikady         
James Cook University Hospital Recruiting
Middlesbrough, United Kingdom
Principal Investigator: Patrick Chiam         
Queen's Medical Centre Recruiting
Nottingham, United Kingdom
Principal Investigator: Austin Acheson         
Pennine Acute Hospitals Recruiting
Oldham, United Kingdom
Principal Investigator: Zahid Hussain         
John Radcliffe Hospital Recruiting
Oxford, United Kingdom
Principal Investigator: Ian Lindsey         
Peterborough and Stamford Hospitals Recruiting
Peterborough, United Kingdom
Principal Investigator: Alexander Hardy         
Salford Royal Recruiting
Salford, United Kingdom
Principal Investigator: Manju Patel         
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         
Morriston Hospital Recruiting
Swansea, United Kingdom
Principal Investigator: Simon Ford         
Royal Cornwall Hospital Recruiting
Truro, United Kingdom
Contact: Catherine Ralph         
Principal Investigator: Catherine Ralph         
Sponsors and Collaborators
University College, London
Investigators
Principal Investigator: Toby Richards, MD FRCS University College, London
More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01692418     History of Changes
Other Study ID Numbers: 12/0246
2012-002786-35 ( EudraCT Number )
10/104/06 ( Other Grant/Funding Number: NIHR HTA )
12/EE/0445 ( Other Identifier: REC )
ISRCTN67322816 ( Registry Identifier: ISRCTN )
First Posted: September 25, 2012    Key Record Dates
Last Update Posted: October 30, 2017
Last Verified: October 2017

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

Additional relevant MeSH terms:
Anemia
Hematologic Diseases
Ferric Compounds
Hematinics