Ferric Carboxymaltose Methemoglobinemia Study

NCT06958822 | Completed FDA Drug

• 1 other identifier: 2024-KAEK-30 / 2025-43
• Study Type: observational
• Target: 977
• Locations: 1 country
• Sites: 23

Brief Summary

Anemia that develops due to iron deficiency is called iron deficiency anemia. This common condition is treated with iron supplements taken either orally or given through an intravenous (IV) infusion. Ferric carboxymaltose (FCM) is one of the widely used, comparably newer IV iron preparations. Recently, several publications have raised the possibility that FCM may be associated with mild elevations in methemoglobin (metHb), a form of hemoglobin that cannot effectively deliver oxygen to tissues. Methemoglobinemia is a known, though uncommon, side effect of some drugs. While usually mild and self-limiting, in certain cases it can become clinically significant or even life-threatening. This observational study is being conducted across multiple centers to better understand how often methemoglobinemia occurs after administration of FCM. As part of routine care, venous blood samples will be used to measure metHb levels in patients receiving FCM, and these results will be compared with those from individuals not exposed to the drug.

Conditions

Methemoglobinemia; Anemia, Iron-Deficiency; Parenteral Iron Therapy; Ferric Carboxymaltose

Keywords

iron deficiency anemia; ferric carboxymaltose; intravenous iron; methemoglobinemia

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Treatment-Related Clinically Significant Methemoglobinemia

  Methemoglobin levels will be measured just before the infusion and at the 15th and 30th minutes post-infusion through venous sampling. The levels equal to or above 3% will be regarded as clinically significant methemoglobinemia.

  From the time of enrollment through 30 minutes following completion of the infusion. If methemoglobin level is ≥3% after infusion, blood sampling will continue every half hour after the last blood gas for 24 hours until methemoglobinemia is <3%.

Study Arms (2)

FCM Group

It will represent the group of patients who will be administered ferric carboxymaltose (FCM), i.e., the exposed group.

Drug: Ferric Carboxymaltose (FCM)

Control Group

It will represent the control group of patients who do not receive FCM or any form of iron therapy, i.e., the unexposed group.

Interventions

Ferric Carboxymaltose (FCM) DRUG

As this is an observational study, ferric carboxymaltose recipients are determined based on routine medical care practices. The researchers do not define which participants will receive ferric carboxymaltose.

FCM Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study participants will consist of persons admitted to a total of 21 different secondary or tertiary care hospitals in 16 different provinces across Turkey.

You may qualify if:

• FCM Group:
• Adults (≥18 years)
• Presence of anemia (Hb \<12 g/dl in women, \<13 g/dl in men)
• Low ferritin (\<30 mcg/l)
• Patients for whom FCM administration has been decided in routine medical care practice
• Control Group:
• Healthy adult (≥18 years) individuals who applied to the internal medicine outpatient clinic, who had no current or pre-existing chronic disease, who did not have anemia and iron deficiency (ferritin ≥30 mcg/L).

You may not qualify if:

• Known methemoglobinemia-related diseases (Hb M disease, cytochrome b5 reductase deficiency, etc.)
• Use of drugs associated with methemoglobinemia (acetylsalicylic acid, dapsone, chloroquine, metoclopramide, benzocaine, lidocaine, prilocaine, rasburicase, primaquine, sulfonamide, nitric oxide)
• Those with B12 and/or folate deficiency
• Those with Charlson Comorbidity Index ≥3
• Presence of advanced organ failure (Stage 4 and 5 chronic kidney disease, Child C cirrhosis, NYHA class 3 and 4 chronic heart failure, respiratory failure requiring oxygen supplementation and similar processes)
• Presence of malignancy (with or without cure)
• Presence of active infection (CRP \> 5 mg/dL) and/or other acute disorder/disease
• Pregnancy status

Sponsors & Collaborators

• Ordu University: lead
• Marmara University Pendik Training and Research Hospital: collaborator

Study Sites (23)

University of Health Sciences Adana City Health Application and Research Center

Adana, Adana, 01100, Turkey (Türkiye)

Location

Akdeniz University Hospital

Konyaalti, Antalya, 07070, Turkey (Türkiye)

Location

Balıkesir University Health Practice and Research Hospital

Merkez, Balıkesir, 10145, Turkey (Türkiye)

Location

Bursa City Hospital

Nilufer, Bursa, 16110, Turkey (Türkiye)

Location

University of Health Sciences Diyarbakır Gazi Yaşargil Training and Research Hospital

Kayapınar, Diyarbakır, 21070, Turkey (Türkiye)

Location

Mehmet Yılmaz Aydınlar Acıbadem University

Ataşehir, Istanbul, 34758, Turkey (Türkiye)

Location

Marmara University Training and Research Hospital

Pendik, Istanbul, 34890, Turkey (Türkiye)

Location

Umraniye Training and Research Hospital

Ümraniye, Istanbul, 34764, Turkey (Türkiye)

Location

Izmir Bakircay University Cigli Training and Research Hospital

Çiğli, İzmir, 35610, Turkey (Türkiye)

Location

Karabuk University Training and Research Hospital

Karabük, Karabük Province, 78100, Turkey (Türkiye)

Location

Kayseri City Hospital

Kocasinan, Kayseri, 38080, Turkey (Türkiye)

Location

Antalya City Hospital

Antalya, Kepez, 07080, Turkey (Türkiye)

Location

Bursa Kestel State Hospital

Bursa, Kestel, 16450, Turkey (Türkiye)

Location

Mardin Kızıltepe State Hospital

Mardin, Kızıltepe, 47400, Turkey (Türkiye)

Location

Mardin Artuklu University Training and Research Hospital

Merkez, Mardin, 47100, Turkey (Türkiye)

Location

Ordu University Training and Research Hospital

Altinordu, Ordu, 52200, Turkey (Türkiye)

Location

Recep Tayyip Erdoğan University Faculty of Medicine Training and Research Hospital

Rize, Rize Province, 53100, Turkey (Türkiye)

Location

Sakarya University Training and Research Hospital

Adapazarı, Sakarya, 54100, Turkey (Türkiye)

Location

Siirt University Faculty of Medicine Training and Research Hospital

Siirt, Siirt, 56100, Turkey (Türkiye)

Location

Van Yüzüncü Yıl University Training and Research Hospital

Merkez, Van, 65000, Turkey (Türkiye)

Location

Bursa Yuksek Ihtisas Training and Research

Bursa, Yıldırım, 16310, Turkey (Türkiye)

Location

Çankırı State Hospital

Çankırı, Çankırı, 18100, Turkey (Türkiye)

Location

Çorlu Vatan Hospital

Tekirdağ, Çorlu, 59850, Turkey (Türkiye)

Location

Related Publications (3)

• Tazegul Gokhan, Kimyon Yusuf, Odabasi Zekaver. Ferric carboxymaltose induced methaemoglobinemia: Preliminary data of a novel side effect. 22nd European Congress of Internal Medicine , İstanbul, Turkey, 2024.

  BACKGROUND

• Özbilen M, Savrun ŞT, Aygün A, Kaya Y. P1492: A New Potential And Prevalent Side Effect of Ferric Carboxymaltose: Methemoglobinemia. A Case-Control Study. Hemasphere. 2023 Aug 8;7(Suppl 3):e825173f.

  BACKGROUND

• Ozbilen M, Savrun ST, Aygun A, Kaya Y. Ferric Carboxymaltose-mediated Methemoglobinemia. Curr Drug Saf. 2024;19(1):134-137. doi: 10.2174/1574886318666230213111038.

  PMID: 36779493 BACKGROUND

MeSH Terms

Conditions

Methemoglobinemia; Anemia, Iron-Deficiency

Interventions

ferric carboxymaltose

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia, Hypochromic; Anemia; Iron Deficiencies; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Muhammet Özbilen, MD

  Ordu University Faculty of Medicine

  STUDY DIRECTOR

• Gökhan Tazegül, MD

  Marmara University

  STUDY DIRECTOR

• Volkan Aydın, MD PhD

  Marmara University School of Dentistry

  STUDY DIRECTOR

• Murat Bahadır, MD

  Ordu University Faculty of Medicine, Department of Internal Medicine

  PRINCIPAL INVESTIGATOR

• Bilge Ada Özcan, MD

  Marmara University Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• Mehmet Bankir, MD

  University of Health Sciences Adana City Health Application and Research Center

  PRINCIPAL INVESTIGATOR

• Mehmet Can Erişen, MD

  University of Health Sciences Adana City Health Application and Research Center

  PRINCIPAL INVESTIGATOR

• Nurhayat Özkan Sevencan, MD

  Karabuk University Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• Ceren Çevik, MD

  Karabuk University Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• Aysel Toçoğlu, MD

  Sakarya University Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• Sümeyye Çekiç, MD

  Sakarya University Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• Arzu Denler Kılıç, MD

  Çankırı State Hospital

  PRINCIPAL INVESTIGATOR

• Mehmet Selim Mamiş, MD

  Siirt University Faculty of Medicine Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• Necip Nas, MD

  Siirt University Faculty of Medicine Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• Teslime Ayaz, MD

  Izmir Bakircay University Cigli Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• Barış Emekdaş, MD

  Izmir Bakircay University Cigli Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• İhsan Solmaz, MD

  University of Health Sciences Diyarbakır Gazi Yaşargil Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• Ömer Faruk Alakuş, MD

  University of Health Sciences Diyarbakır Gazi Yaşargil Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• Kamil Konur, MD

  Recep Tayyip Erdoğan University Faculty of Medicine Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• Hasan Sözel, MD

  Akdeniz University Hospital

  PRINCIPAL INVESTIGATOR

• Esin Avşar Küçükkurt, MD

  Akdeniz University Hospital

  PRINCIPAL INVESTIGATOR

• Hacer Şen, MD

  Balıkesir University Health Practice and Research Hospital

  PRINCIPAL INVESTIGATOR

• Özge Kama Başçı, MD

  Balıkesir University Health Practice and Research Hospital

  PRINCIPAL INVESTIGATOR

• Nizameddin Koca, MD

  Bursa City Hospital

  PRINCIPAL INVESTIGATOR

• Fatih İleri, MD

  Bursa City Hospital

  PRINCIPAL INVESTIGATOR

• Banu Açmaz, MD

  Kayseri City Hospital

  PRINCIPAL INVESTIGATOR

• Erdem Aydın, MD

  Kayseri City Hospital

  PRINCIPAL INVESTIGATOR

• İdris Baydar, MD

  Mardin Artuklu University Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• Şengül Baran Yerlikaya, MD

  Mardin Artuklu University Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• Yıldız Okuturlar, MD

  Mehmet Yılmaz Aydınlar Acıbadem University

  PRINCIPAL INVESTIGATOR

• Sibel Serin Ocak, MD

  Umraniye Training and Research Hospita

  PRINCIPAL INVESTIGATOR

• Nur Düzen Oflas, MD

  Van Yüzüncü Yıl University Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• Abdullah Güneş, MD

  Van Yüzüncü Yıl University Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• Nazire Osmançelebioğlu, MD

  Recep Tayyip Erdoğan University Faculty of Medicine Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• Ant Uzay, MD

  Mehmet Yılmaz Aydınlar Acıbadem University

  PRINCIPAL INVESTIGATOR

• Sevgi Gülşen Koç, MD

  Antalya City Hospital

  PRINCIPAL INVESTIGATOR

• Ayşe Karaduru, MD

  Antalya City Hospital

  PRINCIPAL INVESTIGATOR

• Gamze Kocaman, MD

  Bursa Yuksek Ihtisas Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• Ali Erol, MD

  Bursa Yuksek Ihtisas Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• Mehmet Biricik, MD

  Mardin Kiziltepe State Hospital

  PRINCIPAL INVESTIGATOR

• Emine Binnetoğlu, MD

  Çorlu Vatan Hospital

  PRINCIPAL INVESTIGATOR

• Muhammet Fatih Şahin, MD

  Bursa Kestel State Hospital

  PRINCIPAL INVESTIGATOR

• Ebru Çağrı Çakır Özden, MD

  Bursa Kestel State Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Day
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: April 13, 2025
• First Posted: May 6, 2025
• Study Start: April 14, 2025
• Primary Completion: September 30, 2025
• Study Completion: September 30, 2025
• Last Updated: November 19, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 3 months after publication with no end date
• Access Criteria: De-identified individual participant data (IPD) that underlie the results reported in this article (text, tables, figures, and appendices) will be made available to researchers who provide a methodologically sound proposal in order to achieve aims in the approved proposal. Access to the IPD will require prior approval from the principal investigator. Researchers will need to submit a formal data access request including: A detailed research protocol with clear objectives and statistical analysis plan, A data use agreement, Proof of institutional ethics approval (if applicable). Decisions regarding data access will be made by the study's data sharing committee within a reasonable time frame, and applicants will be notified via email. Requests should be directed to: drozbilen@gmail.com Data will be shared via a secure data transfer system or repository, depending on the nature and size of the dataset.

Locations

TU (23)