AnemiaPhase 4NCT02031289
Impact of Preoperative Treatment of Anemia and Iron Deficiency in Cardiac Surgery on Outcome.
A Phase 4 study testing Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic Acid in people with Anemia and Iron Deficiency, run by University of Zurich at 1 site in Switzerland.
Trial summary
We are performing the above prospective randomized trial in 1'000 patients undergoing cardiac surgery. The study will answer the question of whether preoperative treatment of anemia or iron deficiency indeed improves transfusion needs (primary outcome) and important clinical outcomes (secondary outcome) in a large… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anemia, Iron Deficiency
- What is being tested?
- Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic Acid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,003 participants
- Where
- 1 siteSwitzerland
- Study dates
- Dec 2013to May 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing valve- and/or coronary bypass surgery
- Signed patient informed consent
- Only patients will be enrolled who won't have an emergency surgery on the same day
Who cannot join
- Participation in another clinical trial within the last 4 weeks prior to enrollment
- Addiction or other disease that did not allow the patient to assess the nature, scope and possible consequences of the clinical tial
- Patients who do not sign the consent form or may not fully understand from inadequate knowledge of German.
- Patients who have not reached the age of legal majority
- Pregnant or lactating women
- Jehovah's Witnesses
- Patients with endocarditis
- Existing allergy or intolerance to ferric carboxymaltose or mannitol
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
University Hospital Zurich, Institute of Anaesthesiology
Zurich, Canton of Zurich, 8091
About this study
We are performing the above prospective randomized trial in 1'000 patients undergoing cardiac surgery. The study will answer the question of whether preoperative treatment of anemia or iron deficiency indeed improves transfusion needs (primary outcome) and important clinical outcomes (secondary outcome) in a large group of cardiac surgical patients. The list of inclusion and exclusion criteria was deliberately chosen short so that this patient group largely reflects today's clinical practice .
- Trial with medical product
Read the detailed description
Anemic or iron deficiency patients are randomized into treatment and placebo groups. Treatment (see below) will be given the day before the operation (day -1) or a maximum of 2 days prior to the operation (day -2) in iron deficiency patients and a maximum of 3 days prior to the operation in anemic patients (day -3). The treatment will not be disclosed to the patient or the health care workers treating the patients during and after the operation.
Patients without anemia or iron deficiency will also be observed and the same postoperative measurements performed. They will serve as a natural comparison group.
Treatment:
Erythropoietin alpha (Eprex, Janssen-Cilag AG, Baar) 40'000 U sc. Ferric carboxymaltose (Ferinject, Vifor (International) AG, St. Gallen) 1000 mg in 100 ml sodiumchloride (NaCl) over 30 min.
Vitamin B12 (Vitarubin®-superconc., Streuli Pharma AG, Uznach) 1 mg sc. Folic acid (Acidum folicum, Streuli Pharma AG, Uznach) 5 mg po.
The current transfusion and coagulation guidelines of the University Hospital of Zurich are followed in both groups identically. Postoperatively on the regular ward a Hb transfusion trigger of 80 g/L is applied
- Conditions
- Anemia, Iron Deficiency
- Being tested
- Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic Acid
- Keywords
- Anemia, Iron deficiency, Cardiac surgery, Perioperative Care
- Medical subject headings
- Anemia, Iron Deficiencies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic AcidDrug
Also called Eprex, Ferinject, Vitarubin®-superconc, Acidum folicum
Treatment ) will be given the day before the operation (day -1) or a maximum of 2 days prior to the operation (day -2) in iron deficiency patients and a maximum of 3 days prior to the operation in anemic patients (day -3).
Erythropoietin alpha (Eprex, Janssen-Cilag AG, Baar) 40'000 U sc. Ferric carboxymaltose (Ferinject, Vifor (International) AG, St. Gallen) 1000 mg in 100 ml NaCl over 30 min.
Vitamin B12 (Vitarubin®-superconc., Streuli Pharma AG, Uznach) 1 mg sc. Folic acid (Acidum folicum, Streuli Pharma AG, Uznach) 5 mg po.
| Study group | Role | What they receive |
|---|---|---|
| Anemia | Active comparator | Hb < 120 g/L in women, Hb < 130 g/L in men Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic Acid Receives: Drug: Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic Acid |
| Iron deficiency | Active comparator | ferritin < 100 µg/l Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic Acid Receives: Drug: Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic Acid |
| Natural comparison group | No intervention | Patients without anemia or iron deficiency will be observed and the same postoperative measurements performed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Red blood cell (RBC) units transfused
Measured: 7 days
Secondary outcomes (18)
Percentage of patients without any RBC transfusions
Measured: 90 days
Combined allogeneic transfusions (RBC, FFP( fresh frozen plasma), platelets)
Measured: 90 days
Length of stay in the intensive care unit (ICU)
Measured: 90 days
Duration of mechanical ventilation
Measured: 90 days
Acute kidney failure
RIFLE I, AKIN 2
Measured: 7 days
Major Adverse Cardiac and Cerebrovascular Events (MACCE)
Myocardial infarction, stroke, death
Measured: 90 days
New atrial fibrillation
Measured: 90 days
Infections
Pneumonia, hospital acquired Deep Sternal Wound Infection
Definition of infection: rise in inflammation markers after the initial postoperative period (acute phase reaction) and requires treatment and/ or prolongs days in hospital and/or microbiological confirmation of infection
Measured: 7 days
Thrombotic and thromboembolic complications (90 days)
clinical symptoms and evidence of thrombosis/ embolism in one of the following imaging methods (ultrasound, CT-scan)
Measured: 90 days
Length of stay (LOS) in the hospital
Measured: 90 days
Length of hospital stay (in comparison to median LOS published for relevant Swiss-DRGs)
Measured: 90 days
In hospital mortality
Measured: 90 days
30 day and 90-day mortality
Measured: 90 days
Costs (for blood products and pharmaceutical products related to transfusion and anemia management)
Comparison of costs for study medication versus costs for blood products and products related to transfusion
Measured: 90 days
Perioperative Hb concentrations
Measured: 90 days
Calculated RBC and blood loss
Measured: 90 days
Comparison of the treatment and placebo groups with the natural comparison group
Measured: 90 days
Safety and tolerance of administered study drug and placebo
Comparison of all serious adverse events between study drug group and placebo group
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2014 (estimated)
- Study startDec 2013
- Primary completionDec 2017
- Study completionMay 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AnemiaStudies of the same condition, open and under way.
- More trials run by University of ZurichThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,003 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Donat R Spahn, Prof MD, Principal investigator, University Hospital Zurich, Institute of Anaesthesiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02031289
- Sponsor's protocol ID
- IFA2012/IDCS
- Status last verified
- May 2018
- First submitted
- 16 Dec 2013
- Last updated
- 11 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Rossler J, Schoenrath F, Seifert B, Kaserer A, Spahn GH, Falk V, Spahn DR. Iron deficiency is associated with higher mortality in patients undergoing cardiac surgery: a prospective study. Br J Anaesth. 2020 Jan;124(1):25-34. doi: 10.1016/j.bja.2019.09.016. Epub 2019 Oct 24.
PubMed 31668348Spahn DR, Schoenrath F, Spahn GH, Seifert B, Stein P, Theusinger OM, Kaserer A, Hegemann I, Hofmann A, Maisano F, Falk V. Effect of ultra-short-term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery: a prospective randomised trial. Lancet. 2019 Jun 1;393(10187):2201-2212. doi: 10.1016/S0140-6736(18)32555-8. Epub 2019 Apr 26.
PubMed 31036337
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Preoperative Treatment of Anemia and Iron Deficiency in Cardiac Surgery on Outcome.
- ClinicalTrials.gov ID
- NCT02031289
- Acronym / sponsor ID
- IFA2012/IDCS
- Conditions
- Anemia, Iron Deficiency
- Keywords
- Anemia, Iron deficiency, Cardiac surgery, Perioperative Care
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,003 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- Dec 2013
- Primary completion
- Dec 2017 (actual)
- Study completion
- May 2018 (actual)
- First posted
- 9 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
We are performing the above prospective randomized trial in 1'000 patients undergoing cardiac surgery. The study will answer the question of whether preoperative treatment of anemia or iron deficiency indeed improves transfusion needs (primary outcome) and important clinical outcomes (secondary outcome) in a large group of cardiac surgical patients. The list of inclusion and exclusion criteria was deliberately chosen short so that this patient group largely reflects today's clinical practice .
- Trial with medical product
Detailed description
Anemic or iron deficiency patients are randomized into treatment and placebo groups. Treatment (see below) will be given the day before the operation (day -1) or a maximum of 2 days prior to the operation (day -2) in iron deficiency patients and a maximum of 3 days prior to the operation in anemic patients (day -3). The treatment will not be disclosed to the patient or the health care workers treating the patients during and after the operation.
Patients without anemia or iron deficiency will also be observed and the same postoperative measurements performed. They will serve as a natural comparison group.
Treatment:
Erythropoietin alpha (Eprex, Janssen-Cilag AG, Baar) 40'000 U sc. Ferric carboxymaltose (Ferinject, Vifor (International) AG, St. Gallen) 1000 mg in 100 ml sodiumchloride (NaCl) over 30 min.
Vitamin B12 (Vitarubin®-superconc., Streuli Pharma AG, Uznach) 1 mg sc. Folic acid (Acidum folicum, Streuli Pharma AG, Uznach) 5 mg po.
The current transfusion and coagulation guidelines of the University Hospital of Zurich are followed in both groups identically. Postoperatively on the regular ward a Hb transfusion trigger of 80 g/L is applied
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Anemia | Active comparator | Drug: Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic AcidHb < 120 g/L in women, Hb < 130 g/L in men Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic Acid |
| Iron deficiency | Active comparator | Drug: Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic Acidferritin < 100 µg/l Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic Acid |
| Natural comparison group | No intervention | –Patients without anemia or iron deficiency will be observed and the same postoperative measurements performed |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients undergoing valve- and/or coronary bypass surgery
- Signed patient informed consent
- Only patients will be enrolled who won't have an emergency surgery on the same day
Key exclusion criteria (8 listed)
- Participation in another clinical trial within the last 4 weeks prior to enrollment
- Addiction or other disease that did not allow the patient to assess the nature, scope and possible consequences of the clinical tial
- Patients who do not sign the consent form or may not fully understand from inadequate knowledge of German.
- Patients who have not reached the age of legal majority
- Pregnant or lactating women
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic AcidAlso: Eprex, Ferinject, Vitarubin®-superconc, Acidum folicumTreatment ) will be given the day before the operation (day -1) or a maximum of 2 days prior to the operation (day -2) in iron deficiency patients and a maximum of 3 days prior to the operation in anemic patients (day -3). Erythropoietin alpha (Eprex, Janssen-Cilag AG, Baar) 40'000 U sc. Ferric carboxymaltose (Ferinject, Vifor (International) AG, St. Gallen) 1000 mg in 100 ml NaCl over 30 min. Vitamin B12 (Vitarubin®-superconc., Streuli Pharma AG, Uznach) 1 mg sc. Folic acid (Acidum folicum, Streuli Pharma AG, Uznach) 5 mg po. | Drug | Anemia, Iron deficiency |
Primary outcome
Red blood cell (RBC) units transfused
Time frame: 7 days
18 secondary outcomes
Percentage of patients without any RBC transfusions
Time frame: 90 days
Combined allogeneic transfusions (RBC, FFP( fresh frozen plasma), platelets)
Time frame: 90 days
Length of stay in the intensive care unit (ICU)
Time frame: 90 days
Duration of mechanical ventilation
Time frame: 90 days
Acute kidney failure
Time frame: 7 days
Major Adverse Cardiac and Cerebrovascular Events (MACCE)
Time frame: 90 days
New atrial fibrillation
Time frame: 90 days
Infections
Time frame: 7 days
Thrombotic and thromboembolic complications (90 days)
Time frame: 90 days
Length of stay (LOS) in the hospital
Time frame: 90 days
Length of hospital stay (in comparison to median LOS published for relevant Swiss-DRGs)
Time frame: 90 days
In hospital mortality
Time frame: 90 days
30 day and 90-day mortality
Time frame: 90 days
Costs (for blood products and pharmaceutical products related to transfusion and anemia management)
Time frame: 90 days
Perioperative Hb concentrations
Time frame: 90 days
Calculated RBC and blood loss
Time frame: 90 days
Comparison of the treatment and placebo groups with the natural comparison group
Time frame: 90 days
Safety and tolerance of administered study drug and placebo
Time frame: 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2018.
- Derived from this study: PubMed 31668348Rossler J, Schoenrath F, Seifert B, Kaserer A, Spahn GH, Falk V, Spahn DR. Iron deficiency is associated with higher mortality in patients undergoing cardiac surgery: a prospective study. Br J Anaesth. 2020 Jan;124(1):25-34. doi: 10.1016/j.bja.2019.09.016. Epub 2019 Oct 24.
- Derived from this study: PubMed 31036337Spahn DR, Schoenrath F, Spahn GH, Seifert B, Stein P, Theusinger OM, Kaserer A, Hegemann I, Hofmann A, Maisano F, Falk V. Effect of ultra-short-term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery: a prospective randomised trial. Lancet. 2019 Jun 1;393(10187):2201-2212. doi: 10.1016/S0140-6736(18)32555-8. Epub 2019 Apr 26.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Donat R Spahn, Prof MD principal investigator
University Hospital Zurich, Institute of Anaesthesiology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic Acid in people with Anemia and Iron Deficiency, run by University of Zurich at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Red blood cell (RBC) units transfused (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02031289, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2018.