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Anemia PostoperativePhase 4PICSNCT04608539

A Clinical Trial Assessing the Efficacy of Intravenous Iron for the Treatment of Anemia Following Cardiac Surgery

A Phase 4 study testing Ferric Derisomaltose, Ferrous sulfate and normal saline in people with Anemia Postoperative, run by Michael Kremke at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

BACKGROUND Anemia and iron deficiency are highly prevalent in cardiac surgery patients. Both conditions may adversely affect postoperative rehabilitation. At hospital discharge, anemia is almost invariably present due to perioperative blood loss and frequent blood sampling. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Anemia Postoperative
What is being tested?
Ferric Derisomaltose, Ferrous sulfate and normal saline
Could I receive a placebo?
No, everyone receives an active treatment
How many people
110 participants
Where
1 siteDenmark
Study dates
21 May 2021to 27 Jun 2023
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 18 years of age or older undergoing first-time, non-emergent cardiac surgery with cardiopulmonary bypass. Eligible procedures are A: isolated CABG surgery (+/- arrhythmia surgery), B: isolated cardiac valve surgery (+/- arrhythmia surgery), C: a combination of CABG and cardiac valve surgery (+/- arrhythmia surgery)
  • Moderate anaemia on the first postoperative day. According to World Health Organization-criteria defined as a haemoglobin concentration of equal to or greater than 5.0 mmol/l (8 g/dl) and less than 6.8 mmol/l (11 g/dl).

Who cannot join

  • Known hypersensitivity to any iron formulation
  • Multiple drug allergies or history of previous anaphylaxis
  • Severe asthma, eczema or another atopic allergy
  • Rheumatoid arthritis or systemic lupus erythematosus
  • History of iron overload or disturbances in iron utilisation (e.g. haemochromatosis, hemosiderosis)
  • History of liver disease (e.g. cirrhosis)
Show all 16Show fewer
  • Severe active infection or inflammation (e.g. endocarditis)
  • Porphyria cutanea tarda
  • Treatment with intravenous iron within 4 weeks prior to surgery.
  • Untreated vitamin B12 or folate deficiency.
  • Anticipated inability to perform a six-minute walk test.
  • Women of childbearing potential, pregnant and nursing women.
  • Anticipated postoperative length of stay in the intensive care unit (ICU) > 48 hours.
  • Patients incapable of giving consent personally.
  • Significantly increased risk of non-adherence or loss to follow-up.
  • Active participation in another interventional trial with potential impact on postoperative anaemia or exercise capacity.

Trial locations and contacts

1 site in 1 country.

Denmark1 site

  • Aarhus University Hospital

    Aarhus, 8200

Other trials in Denmark

About this study

Official title: The Postoperative Iron in Cardiac Surgery (PICS-) Trial: A Randomised Clinical Trial Comparing the Efficacy of Single-, High-dose Intravenous Iron and Oral Iron for the Treatment of Anaemia Following Cardiac Surgery

BACKGROUND Anemia and iron deficiency are highly prevalent in cardiac surgery patients. Both conditions may adversely affect postoperative rehabilitation.

At hospital discharge, anemia is almost invariably present due to perioperative blood loss and frequent blood sampling. Two previous analyses demonstrated a prevalence of anemia early after coronary artery bypass grafting (CABG) of 94% and 98%, respectively. Almost half of CABG patients had persistent anemia two months after surgery. Postoperative anemia may result in debilitating symptoms, like dyspnoea, fatigue and poor exercise tolerance, and is associated with an increased likelihood of cardiovascular events and death after cardiac surgery.

Read more

Mild to moderate anemia is commonly corrected with oral iron supplements. Oral iron is however poorly absorbed in patients with chronic diseases, and about 40% of patients suffer from debilitating gastrointestinal side-effects. As iron stores are frequently reduced or depleted after cardiac surgery, treatment with oral iron supplements may take several months.

In patients with chronic heart failure (CHF), iron deficiency is associated with reduced exercise capacity, quality of life and survival even in the absence of anemia. Several large randomised trials demonstrated that treatment with intravenous iron improved clinical symptoms, exercise capacity and quality of life of CHF patients.

RATIONALE It is desirable to replenish body iron stores rapidly after cardiac surgery with the aim to effectively correct anemia, optimize exercise tolerance and improve patient wellbeing.

Modern intravenous iron formulations permit fast replenishment of body iron stores and have emerged as potential alternatives to oral iron. These formulations are well-tolerated and have become an established therapeutic option in anemic patients with reduced intestinal iron absorption. Several studies have demonstrated the efficacy of intravenous iron for the treatment of anemia following major non-cardiac surgery.

Data regarding the efficacy of intravenous iron in cardiac surgery, however, are conflicting.

HYPOTHESIS Single-dose intravenous iron therapy with ferric derisomaltose/iron isomaltoside is superior to oral iron supplementation for the correction of anemia following cardiac surgery. Moreover, single-dose intravenous iron therapy with ferric derisomaltose/iron isomaltoside results in a greater postoperative exercise capacity, an improved quality of life and less fatigue.

Being tested
Ferric Derisomaltose, Ferrous sulfate, normal saline
Keywords
Anemia, Iron deficiency, Transfusion, Postoperative period, Rehabilitation
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.

  • Ferric DerisomaltoseDrug

    Also called MonoFer, iron isomaltoside 1000

    Single-dose intravenous infusion, 20 mg/kg body weight, postoperative day 1

  • Ferrous sulfateDrug

    Also called Ferro Duretter

    Oral therapy, 100 mg twice daily, from postoperative day 4 until 4-week follow-up

  • normal salineDrug

    Also called 0.9% natriumchloride

    Single-dose infusion (placebo), postoperative day 1

Study groups in NCT04608539
Study groupRoleWhat they receive
Intravenous iron groupExperimentalSingle-dose intravenous infusion of 20 mg/kg body weight ferric derisomaltose/iron isomaltoside 1000 (MonoFer®)
Receives: Drug: Ferric Derisomaltose
Oral iron groupActive comparatorOral therapy with 100 mg oral ferrous sulfate twice daily
Receives: Drug: Ferrous sulfate; Drug: normal saline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The proportion of participants who are neither anemic nor have received allogeneic red blood cells since randomisation

    Unit: percentage; anemia according to WHO criteria defined as hemoglobin < 12 g/dl in women and < 13 g/dl in men.

    Measured: 4-week follow-up

Secondary outcomes (17)

  1. Mean change in hemoglobin level

    Unit: g/dl

    Measured: From baseline to 4-week follow-up

  2. Proportion of participants with a haemoglobin increase ≥ 1.3 mmol/l (≥ 2 g/dL)

    Unit: %

    Measured: From baseline to 4-week follow-up

  3. Mean haemoglobin level

    Unit: g/dl

    Measured: 4-week follow-up

  4. Mean reticulocyte count

    Unit: 10^9/l

    Measured: 4-week follow-up

  5. Mean plasma iron

    μmol/l

    Measured: 4-week follow-up

  6. Mean plasma ferritin

    µg/l

    Measured: 4-week follow-up

  7. Mean transferrin saturation

    Unit: %

    Measured: 4-week follow-up

  8. Mean change in haemoglobin level

    Unit: g/dl

    Measured: From the day before surgery to 4-week follow-up

  9. Mean change in reticulocyte count

    Unit: 10^9/l

    Measured: From the day before surgery to 4-week follow-up

  10. Mean change in plasma iron

    μmol/l

    Measured: From the day before surgery to 4-week follow-up

  11. Mean change in plasma ferritin

    µg/l

    Measured: From the day before surgery to 4-week follow-up

  12. Mean change in transferrin saturation

    Unit: %

    Measured: From the day before surgery to 4-week follow-up

  13. Proportion of participants transfused with allogeneic red blood cells

    Units: %

    Measured: From the time of randomisation to 4-week follow-up

  14. Six-minute walk distance

    Units: meter

    Measured: 4-week follow-up

  15. Health-related quality of life

    Health-related quality of life is assessed with the standardized European Quality of Life (EuroQol) Group five dimensions questionnaire (EQ-5D). The outcome of interest is the visual analogue scale (EQ VAS). The 5-level EQ-5D (EQ-5D-5L) consists of a descriptive system and the EQ VAS. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the best endpoint is "100" and the worst "0".

    Measured: 4-week follow-up

  16. Fatique

    Fatigue is assessed using the validated Multidimensional Fatigue Inventory (MFI-20). The outcome of interest is physical fatigue. The MFI-20 consists of 20 items for the assessment of fatigue in five different dimensions: general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. Each dimension contains four items for which participants have to indicate on a five-point scale how the particular statement suited their experience. An equal number of items are worded in a positive and a negative way to counteract for response tendencies. A score of four indicates no presence of fatigue, while a score of 20 indicates the highest level of fatigue.

    Measured: 4-week follow-up

  17. New York Heart Association (NYHA) functional class

    Assessing symptoms (i.e. angina and dyspnea) and the resulting limitations during ordinary physical activity. Class I-IV. I=no symptoms, higher classes are associated with more severe symptoms and limitations. IV=severe symptoms and limitations. The outcome of interest is the proportion of participants with a NYHA functional class of I.

    Measured: 4-week follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Oct 2020
  2. Study start21 May 2021
  3. Primary completion27 Jun 2023
  4. Study completion27 Jun 2023

Resources

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
None (open label)
Enrolment
110 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04608539
Sponsor's protocol ID
PICS-01
Acronym
PICS
Status last verified
Jun 2023
First submitted
17 Sep 2020
Last updated
28 Jun 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Hogan M, Klein AA, Richards T. The impact of anaemia and intravenous iron replacement therapy on outcomes in cardiac surgery. Eur J Cardiothorac Surg. 2015 Feb;47(2):218-26. doi: 10.1093/ejcts/ezu200. Epub 2014 May 13.

    PubMed 24824650

  • Tramarin R, Pistuddi V, Maresca L, Pavesi M, Castelvecchio S, Menicanti L, de Vincentiis C, Ranucci M; Surgical and Clinical Outcome Research (SCORE) Group. Patterns and determinants of functional and absolute iron deficiency in patients undergoing cardiac rehabilitation following heart surgery. Eur J Prev Cardiol. 2017 May;24(8):799-807. doi: 10.1177/2047487317689975. Epub 2017 Jan 24.

    PubMed 28117617

  • Westenbrink BD, Kleijn L, de Boer RA, Tijssen JG, Warnica WJ, Baillot R, Rouleau JL, van Gilst WH; IMAGINE Investigators. Sustained postoperative anaemia is associated with an impaired outcome after coronary artery bypass graft surgery: insights from the IMAGINE trial. Heart. 2011 Oct;97(19):1590-6. doi: 10.1136/heartjnl-2011-300118. Epub 2011 Jul 13.

    PubMed 21757458

  • Ranucci M, La Rovere MT, Castelvecchio S, Maestri R, Menicanti L, Frigiola A, D'Armini AM, Goggi C, Tramarin R, Febo O. Postoperative anemia and exercise tolerance after cardiac operations in patients without transfusion: what hemoglobin level is acceptable? Ann Thorac Surg. 2011 Jul;92(1):25-31. doi: 10.1016/j.athoracsur.2011.02.058. Epub 2011 May 18.

    PubMed 21592458

  • Society of Thoracic Surgeons Blood Conservation Guideline Task Force; Ferraris VA, Brown JR, Despotis GJ, Hammon JW, Reece TB, Saha SP, Song HK, Clough ER; Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion; Shore-Lesserson LJ, Goodnough LT, Mazer CD, Shander A, Stafford-Smith M, Waters J; International Consortium for Evidence Based Perfusion; Baker RA, Dickinson TA, FitzGerald DJ, Likosky DS, Shann KG. 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg. 2011 Mar;91(3):944-82. doi: 10.1016/j.athoracsur.2010.11.078.

    PubMed 21353044

  • Task Force on Patient Blood Management for Adult Cardiac Surgery of the European Association for Cardio-Thoracic Surgery (EACTS) and the European Association of Cardiothoracic Anaesthesiology (EACTA); Boer C, Meesters MI, Milojevic M, Benedetto U, Bolliger D, von Heymann C, Jeppsson A, Koster A, Osnabrugge RL, Ranucci M, Ravn HB, Vonk ABA, Wahba A, Pagano D. 2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery. J Cardiothorac Vasc Anesth. 2018 Feb;32(1):88-120. doi: 10.1053/j.jvca.2017.06.026. Epub 2017 Sep 30. No abstract available.

    PubMed 29029990

  • Mazer CD, Whitlock RP, Fergusson DA, Belley-Cote E, Connolly K, Khanykin B, Gregory AJ, de Medicis E, Carrier FM, McGuinness S, Young PJ, Byrne K, Villar JC, Royse A, Grocott HP, Seeberger MD, Mehta C, Lellouche F, Hare GMT, Painter TW, Fremes S, Syed S, Bagshaw SM, Hwang NC, Royse C, Hall J, Dai D, Mistry N, Thorpe K, Verma S, Juni P, Shehata N; TRICS Investigators and Perioperative Anesthesia Clinical Trials Group. Six-Month Outcomes after Restrictive or Liberal Transfusion for Cardiac Surgery. N Engl J Med. 2018 Sep 27;379(13):1224-1233. doi: 10.1056/NEJMoa1808561. Epub 2018 Aug 26.

    PubMed 30146969

  • Tolkien Z, Stecher L, Mander AP, Pereira DI, Powell JJ. Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis. PLoS One. 2015 Feb 20;10(2):e0117383. doi: 10.1371/journal.pone.0117383. eCollection 2015.

    PubMed 25700159

  • Piednoir P, Allou N, Driss F, Longrois D, Philip I, Beaumont C, Montravers P, Lasocki S. Preoperative iron deficiency increases transfusion requirements and fatigue in cardiac surgery patients: a prospective observational study. Eur J Anaesthesiol. 2011 Nov;28(11):796-801. doi: 10.1097/EJA.0b013e32834ad97b.

    PubMed 21885979

  • Camaschella C. Iron-deficiency anemia. N Engl J Med. 2015 May 7;372(19):1832-43. doi: 10.1056/NEJMra1401038. No abstract available.

    PubMed 25946282

  • Jankowska EA, Malyszko J, Ardehali H, Koc-Zorawska E, Banasiak W, von Haehling S, Macdougall IC, Weiss G, McMurray JJ, Anker SD, Gheorghiade M, Ponikowski P. Iron status in patients with chronic heart failure. Eur Heart J. 2013 Mar;34(11):827-34. doi: 10.1093/eurheartj/ehs377. Epub 2012 Nov 23.

    PubMed 23178646

  • von Haehling S, Ebner N, Evertz R, Ponikowski P, Anker SD. Iron Deficiency in Heart Failure: An Overview. JACC Heart Fail. 2019 Jan;7(1):36-46. doi: 10.1016/j.jchf.2018.07.015. Epub 2018 Dec 12.

    PubMed 30553903

  • Enjuanes C, Klip IT, Bruguera J, Cladellas M, Ponikowski P, Banasiak W, van Veldhuisen DJ, van der Meer P, Jankowska EA, Comin-Colet J. Iron deficiency and health-related quality of life in chronic heart failure: results from a multicenter European study. Int J Cardiol. 2014 Jun 15;174(2):268-75. doi: 10.1016/j.ijcard.2014.03.169. Epub 2014 Apr 3.

    PubMed 24768464

  • Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Luscher TF, Bart B, Banasiak W, Niegowska J, Kirwan BA, Mori C, von Eisenhart Rothe B, Pocock SJ, Poole-Wilson PA, Ponikowski P; FAIR-HF Trial Investigators. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009 Dec 17;361(25):2436-48. doi: 10.1056/NEJMoa0908355. Epub 2009 Nov 17.

    PubMed 19920054

  • Ponikowski P, van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V, McDonagh T, Parkhomenko A, Tavazzi L, Levesque V, Mori C, Roubert B, Filippatos G, Ruschitzka F, Anker SD; CONFIRM-HF Investigators. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiencydagger. Eur Heart J. 2015 Mar 14;36(11):657-68. doi: 10.1093/eurheartj/ehu385. Epub 2014 Aug 31.

    PubMed 25176939

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Ferric Derisomaltose, Ferrous sulfate and normal saline in people with Anemia Postoperative, run by Michael Kremke at 1 site in Denmark.

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 2 inclusion and 16 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 28 Jun 2023. 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 Denmark. 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?

The proportion of participants who are neither anemic nor have received allogeneic red blood cells since randomisation (time frame: 4-week follow-up). 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 NCT04608539, which also lists 18 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 28 Jun 2023.

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