Plain English Summary
Background and study aims
About 25% of patients undergoing planned, elective heart surgery have an abnormally low blood count (hemoglobin). These patients are more likely to need a blood transfusion during and after surgery. They are also more likely to have complications after surgery. Most patients who have a low blood count have low levels of iron. Iron treatment in these patients can increase the blood count if it is given several weeks before surgery. Undergoing surgery at a higher blood count will lower the risk of needing a blood transfusion after surgery. The standard method of treating low iron is to take iron tablets, but iron can also be given by injection and this might be more effective. Additionally, drugs such as darbepoetin that stimulate the bone marrow can speed up the increase in blood count. This study will test whether the combination of intravenous iron and darbepoetin will more effectively raise the blood count before surgery and lead to a lower rate of blood transfusion compared to taking iron tablets alone.
Who can participate?
Patients undergoing elective heart surgery at our institution.
What does the study involve?
Patients who are seen in the outpatient clinic when first referred for surgery have their hemoglobin (Hb) level measured routinely. Those with an Hb between 10 and 13 g/dl will be invited to participate in the study. Tests will be performed to measure iron levels in the blood. Those with a low iron level will be randomly allocated to either iron tablets or to attend the hospital for a few hours to receive intravenous iron and darbepoetin. The participants will be scheduled for surgery in the usual way between 2 and 10 weeks after the start of iron treatment. During and after surgery, participants will be looked after according to our normal practice. Red blood cells will be transfused when the Hb is less than 7 g/dl, or higher if there are specific clinical reasons. In addition to monitoring for serious complications after surgery, we will assess the participants' general well being, mental function, mood and fatigue levels before and after iron treatment and after surgery.
What are the possible benefits and risks of participating?
Benefits include investigation and treatment of low Hb level before surgery. A higher Hb before surgery will decrease blood transfusion and may reduce postoperative complications. Risks include side effects from oral iron - constipation or diarrhoea may occur occasionally. Intravenous iron can cause blood pressure to increase or fall during infusion, muscle aches the following days, and very rarely an allergic reaction which may require hospital admission and antihistamine drugs to be given.
Where is the study run from?
The Royal Sussex County Hospital in Brighton (UK)
When is the study starting and how long is it expected to run for?
September 2012 to May 2017
Who is funding the study?
Royal College of Surgeons of England (UK), Sussex Heart Charity (UK) and Pharmacosmos A/S (Denmark)
Who is the main contact?
Dr Robert Kong
robert.kong@bsuh.nhs.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Robert Kong
ORCID ID
Contact details
Department of Anaesthesia
Royal Sussex County Hospital
Eastern Road
Brighton
BN2 5BE
United Kingdom
-
robert.kong@bsuh.nhs.uk
Additional identifiers
EudraCT number
2011-003695-36
ClinicalTrials.gov number
Protocol/serial number
11/104KON
Study information
Scientific title
Is intravenous iron and darbepoetin more effective than oral iron in reducing blood transfusion requirements for patients undergoing cardiac surgery? A pragmatic randomised trial
Acronym
INITIATE
Study hypothesis
In patients who have a low hemoglobin before elective cardiac surgery, treatment with a combination of intravenous iron and darbepoetin several weeks before surgery will reduce perioperative red cell transfusion compared to oral iron alone.
Ethics approval
NRES Committee London - Bentham, 11/01/2012, ref: 11/LO/1310
Study design
Pragmatic open-label randomised parallel group trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Preoperative anemia, cardiac surgery
Intervention
1. Monofer® [iron isomaltoside 1000] 1000mg, single dose, i.v. (or Ferinject® [ferric carboxymaltose] 1000mg, single dose i.v. if Monofer® contraindicated) AND Aranesp® (darbepoetin) 200 µg, single dose, s.c.
2. Compared to ferrous sulphate 200mg, three times daily, oral
Intervention type
Drug
Phase
Not Applicable
Drug names
Iron isomaltoside, ferric carboxymaltose, darbepoetin, ferrous sulphate
Primary outcome measure
Proportion of participants in each study arm that receives one or more packed red cell transfusion between the start of surgery until the end of the fifth postoperative day
Secondary outcome measures
1. Hemoglobin increase between randomisation and surgery
2. Total number of packs and volume of red cells transfused from the start of surgery until hospital discharge
3. Postoperative blood loss at 12 and 24 hours after surgery
4. Significant postoperative myocardial injury as measured by Troponin level 18-24h after surgery
5. Acute renal failure as defined by greater than 1.5 times increase in creatinine level after surgery
6. Length of hospital stay
Overall trial start date
15/09/2012
Overall trial end date
16/05/2019
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Preoperative Hb 10-13 g/dl
2. Serum ferritin <100µg/l or 100-800 µg/L with transferrin saturation <30%
3. First time cardiac surgery involving one or more of the following: coronary artery bypass grafting, repair or replacement of cardiac valve/s or ascending aorta
4. Surgery is elective - not an emergency or patient is not an inpatient immediately prior to surgery
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
320
Participant exclusion criteria
1. Hb <10 g/dl or >13 g/dl
2. Patient intends to refuse allogeneic blood transfusion
3. Patient is receiving renal replacement therapy (peritoneal or hemodialysis) before surgery
4. Patient has a history of allergic or toxic reaction to any of the study drugs
5. Patient has significant acute or chronic hepatic disease
6. Patient is undergoing chemotherapy
7. Redo cardiac surgery (i.e. second time or more)
8. Proposed surgery will require hypothermic circulatory arrest
9. Pregnant
10. Age <18
11. Lacks mental capacity to give consent
12. Already participating in another clinical trial that could interfere with this study
Recruitment start date
15/09/2012
Recruitment end date
30/05/2017
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Royal Sussex County Hospital
Brighton
BN2 5BE
United Kingdom
Sponsor information
Organisation
Brighton & Sussex University Hospitals NHS Trust (UK)
Sponsor details
c/o R & D Manager
Royal Sussex County Hospital
Eastern Road
Brighton
BN2 5BE
United Kingdom
-
robert.kong@bsuh.nhs.uk
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Research organisation
Funder name
Royal College of Surgeons of England (UK)
Alternative name(s)
RCS
Funding Body Type
private sector organisation
Funding Body Subtype
Associations and societies (private and public)
Location
United Kingdom
Funder name
Sussex Heart Charity (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Pharmacosmos A/S (Denmark)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-003695-36/results
Publication list