Is intravenous iron and darbepoetin more effective than oral iron in reducing blood transfusion requirements for patients undergoing cardiac surgery?
| ISRCTN | ISRCTN41421863 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN41421863 |
| Clinical Trials Information System (CTIS) | 2011-003695-36 |
| Protocol serial number | 11/104KON |
| Sponsor | Brighton & Sussex University Hospitals NHS Trust (UK) |
| Funders | Royal College of Surgeons of England (UK), Sussex Heart Charity (UK), Pharmacosmos A/S (Denmark) |
- Submission date
- 23/07/2012
- Registration date
- 28/08/2012
- Last edited
- 09/09/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Surgery
Plain English summary of protocol
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
Contact information
Scientific
Department of Anaesthesia
Royal Sussex County Hospital
Eastern Road
Brighton
BN2 5BE
United Kingdom
| robert.kong@bsuh.nhs.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Pragmatic open-label randomised parallel group trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| 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 |
| Study acronym | INITIATE |
| Study objectives | 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(s) | NRES Committee London - Bentham, 11/01/2012, ref: 11/LO/1310 |
| Health condition(s) or problem(s) studied | 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 / device / biological / vaccine name(s) | Iron isomaltoside, ferric carboxymaltose, darbepoetin, ferrous sulphate |
| Primary outcome measure(s) |
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 |
| Key secondary outcome measure(s) |
1. Hemoglobin increase between randomisation and surgery |
| Completion date | 16/05/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | All |
| Target sample size at registration | 320 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 15/09/2012 |
| Date of final enrolment | 30/05/2017 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
BN2 5BE
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | No | No | |||
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
09/09/2020: The following changes have been made:
1. The overall trial end date has been changed from 23/08/2018 to 16/05/2019.
2. The EudraCT number has been added.
3. A EudraCT link has been added to the basic results summary.
02/07/2019: The following changes were made:
1. The recruitment end date was changed from 30/03/2017 to 30/05/2017.
2. The overall trial end date was changed from 31/05/2017 to 23/08/2018.
05/09/2016: the following changes were made to the trial record:
1. The recruitment end date was changed from 14/09/2015 to 30/03/2017.
2. The overall trial end date was changed from 14/09/2015 to 31/05/2017.
