Clinical trial NCT01692418: Preoperative Intravenous Iron to Treat Anaemia in Major Surgery
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anaemia
Keywords: Anaemia
Blood transfusion
Surgery
Iron
Ferric carboxymaltose
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2012-09-25
Enrollment: 487
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Risk of blood transfusion or death
timeFrame: From randomisation until 30-days following the index operation
measure: Blood transfusion rate (including repeat transfusions)
timeFrame: From randomisation until 30-days following the index operation
Secondary outcomes:
measure: Change in haemoglobin levels
timeFrame: From randomisation to (i) day of index operation, (ii) 8-weeks post index operation and (iii) 6 months post index operation
measure: Total number of units of blood or blood products cross matched, total number of packed red cells and any blood products transfused
timeFrame: From randomisation to 30 days post index operation
measure: Post operative morbidity survey (POMS) outcomes (outcomes will be presence of morbidity defined by the domains of the POMS e.g. gastrointestinal, cardiovascular)
timeFrame: At days 3, 5, 7 and 14 following the index operation
measure: Health-related quality of life: Change in The Multidimensional Fatigue Inventory (MFI) questionnaire total score
timeFrame: From baseline to the 10 day assessment and at 8 weeks and 6 months post operatively
measure: Health-related quality of life: Change in European Quality of Life: 5 Dimensions-5 Levels (EQ-5D-5L) questionnaire total score
timeFrame: From baseline to the 10 day assessment and at 8 weeks and six months post operatively
measure: Health-related quality of life: Change in Single Question Outcome Measure (SQOM)
timeFrame: From baseline to the 10 day assessment and at 8 weeks and six months post operatively
measure: Health resource utilisation
timeFrame: Pre-admission, during admission for index operation, 8 weeks post index operation, and 6 months post index operation
measure: Calculated direct, indirect and total costs for the NHS from two perspectives (payer's and societal perspective)
timeFrame: From baseline to 6 months post-surgery
measure: Cost effectiveness of treatment options using relevant effectiveness parameters
timeFrame: From baseline to 6 months post-surgery
measure: Any reaction or side effect from trial therapy
measure: Any reaction or side effect from whole blood or blood product, transfusion reaction
measure: Serious Adverse Events (SAEs) and Suspected Unexpected Serious Adverse Reactions (SUSARs)
measure: Length of hospital stay
measure: Mortality
timeFrame: 8 weeks and 6 months post-operatively
measure: Readmission
timeFrame: Within 8 weeks and within 6 months of the index operation
measure: Blood transfusion
timeFrame: From randomisation to 8 weeks and 6 months post-operatively
measure: Change in e-GFR
Other outcomes:
Locations:
city: Basildon
country: United Kingdom
facility: Basildon University Hospital
city: Blackpool
country: United Kingdom
facility: Blackpool Teaching Hospitals
city: Bristol
country: United Kingdom
facility: Southmead Hospital
city: Broomfield
country: United Kingdom
facility: Broomfield Hospital
city: Chester
country: United Kingdom
facility: Countess of Chester Hospital
city: Dudley
country: United Kingdom
facility: Russells Hall Hospital
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: Gateshead
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Hereford
country: United Kingdom
facility: Hereford County Hospital
city: Hillingdon
country: United Kingdom
facility: Hillingdon Hospital
city: Leeds
country: United Kingdom
facility: St James's Hospital
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital
city: Liverpool
country: United Kingdom
facility: Liverpool Women's Hospital
city: London
country: United Kingdom
facility: University College London
city: London
country: United Kingdom
facility: Guy's and St Thomas' Hospital
city: London
country: United Kingdom
facility: Imperial College Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Royal Marsden
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre
city: Oldham
country: United Kingdom
facility: Pennine Acute Hospitals
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
city: Peterborough
country: United Kingdom
facility: Peterborough and Stamford Hospitals
city: Salford
country: United Kingdom
facility: Salford Royal
city: Sheffield
country: United Kingdom
facility: Northern General Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Swansea
country: United Kingdom
facility: Morriston Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
Study officials:
affiliation: University College, London
name: Toby Richards, MD FRCS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Richards T, Baikady RR, Clevenger B, Butcher A, Abeysiri S, Chau M, Swinson R, Collier T, Dodd M, Dyck LV, Macdougall I, Murphy G, Browne J, Bradbury A, Klein A. Preoperative intravenous iron for anaemia in elective major open abdominal surgery: the PREVENTT RCT. Health Technol Assess. 2021 Feb;25(11):1-58. doi: 10.3310/hta25110.
citation: Richards T, Clevenger B, Keidan J, Collier T, Klein AA, Anker SD, Kelly JD. PREVENTT: preoperative intravenous iron to treat anaemia in major surgery: study protocol for a randomised controlled trial. Trials. 2015 Jun 4;16:254. doi: 10.1186/s13063-015-0774-2.