Inflammatory Bowel DiseasesOVI-IBDNCT05581420
Oral Versus Intravenous Iron in IBD Patients With Anti-inflammatory Therapy.
A study testing Ferrous fumarate and MonoFer in people with Inflammatory Bowel Diseases, run by Leiden University Medical Center at 1 site in Netherlands.
Trial summary
Rationale: Iron deficiency anemia is the most common systemic manifestation of Inflammatory Bowel Diseases (IBD)-Crohn's disease and ulcerative colitis. Iron deficiency with or without anemia poses a diagnostic and therapeutic challenge due to chronic gastrointestinal blood loss and the inflammatory nature of IBD. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Inflammatory Bowel Diseases
- What is being tested?
- Ferrous fumarate and MonoFer
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 152 participants
- Where
- 1 siteNetherlands
- Study dates
- 2 Jun 2022to May 2025
- Phase
- Interventional
- 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
- Established IBD diagnosis (Crohn's disease, ulcerative colitis, IBD-unclassified)
- Adults (≥18 years of age)
- Any single Hb level between 6,2 - 7,3 mmol/L (females) 6,2 - 8,0 mmol/L (males)
- Any single ferritin <100 μg/L and transferrin saturation <20% within 4 weeks of study inclusion
- CRP > 5 mg/L and / or fecal calprotectin > 150 within 4 weeks of randomization
- Patients on immunosuppressive medication (thiopurine, methotrexate, biologicals, JAK inhibitor) for at least 8 weeks or if prednisone, for at least 2 weeks
- Mild to moderate disease according to the treating physician; a Physician Global Assessment (PGA) score of 1 or 2
- Documented informed consent
Who cannot join
- Anemia due to reasons other than iron deficiency or chronic disease (e.g. hemoglobinopathy).
- Severe disease with a PGA score of 3
- IBD patients with a location of IBD at other places than ileum and / or colon (according to treating physician)
- Patients who are prescribed PPI
- Earlier significant side effect of oral iron or iv iron
- Folic acid deficiency (<2.5 μg/ml)
Show all 14Show fewer
- Vitamin B12 deficiency (<150 mg/l)
- Patients can proceed with their regular diet, but during the study they cannot take supplements that contain iron. For example, commercial vitamins with iron or a well-known iron supplement Floradix®. Intake of said supplements must be stopped at the moment of inclusion.
- Documented history of bariatric surgery or gastric/duodenal resections due to benign or malignant pathologies
- Documented major operation (e.g., laparotomy) less than six weeks before inclusion
- Documented history of liver cirrhosis, heart failure, hemoglobinopathies, autoimmune hemolytic anemia, myelodysplastic syndrome, or chronic obstructive pulmonary disease (COPD)
- Documented history of recent treatment for a malignancy (excluding dermatological malignancies such as basal cell carcinoma or squamous cell carcinoma). Patients can be included if the treatment for malignancy has been finalized ≥6 months before the inclusion date.
- End-stage renal disease (impaired renal function, defined as eGFR <30 ml/min/1.73m2)
- Documented pregnancy or breastfeeding at the time of inclusion
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Leiden University Medical Centre
Leiden, South Holland, 2300 RC
L.J.M. Koppelman, MSc, 0031715297902, patientenibd@lumc.nl
About this study
Official title: Oral Versus Intravenous Iron in IBD Patients With Anti-inflammatory Therapy
Rationale: Iron deficiency anemia is the most common systemic manifestation of Inflammatory Bowel Diseases (IBD)-Crohn's disease and ulcerative colitis. Iron deficiency with or without anemia poses a diagnostic and therapeutic challenge due to chronic gastrointestinal blood loss and the inflammatory nature of IBD. Oral iron supplementation in active disease states is controversial. Hepcidin levels can be considered as the sum effect of all regulatory processes. Studies suggested that iron stores and hypoxia reduce hepcidin levels even in an inflammatory state. This is also reflected by a study which demonstrated low levels of hepcidin in patients with ferritin levels under 30μg/ml, regardless of disease activity or type. Furthermore, studies show that immunosuppressive medication decrease the level of hepcidin. This raises the question: is oral iron a viable alternative for patients under immunosuppressive treatment for active IBD? Objective: The hypothesis is that patients with mild to moderate IBD activity on immunosuppressive medication, show the same level of Hb increase after 12 weeks after either oral or iv iron supplementation, while the price of oral iron supplementation is significantly lower.
Read the detailed description
Study design: multicenter, prospective randomized non-inferiority study. Study population: Patients with inflammatory bowel disease on immunosuppressive medication with iron deficiency anemia, with increased inflammation parameters, but without an elevated ferritin (<100 μg/L).
Intervention: 152 patients will be randomized to a treatment group with either low dose oral iron or iv iron supplementation.
Main study endpoints: Normalization of Hb concentration (> 7.3 mmol/L (females) or > 8.0 mmol/L (males)) from baseline to week 12 in both oral and iv iron supplementation group.
Patients will receive either oral or intravenous iron therapy. Both therapies will be given according to existing guidelines. Participation to this trial will not increase the frequency of regular follow-up visits for patients. Blood for study measurements will be drawn simultaneously as blood for standard care tests. In addition, three questionnaires will be sent out regarding the patient's quality of life, disease activity, and productivity impairment. Iron therapy and biomaterial acquisition do not increase patients' risk because patients would have to undergo the same tests for standard IBD-care and receive iron therapy outside of the study. The study will be directly beneficial to participating patients because patients will undergo treatment for iron deficiency. The findings might help to develop guidelines for personalized iron therapy in the IBD population.
- Conditions
- Inflammatory Bowel Diseases
- Being tested
- Ferrous fumarate, MonoFer
- Medical subject headings
- Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ferrous fumarateDrug
Patients randomized in the oral group, will all be prescribed ferrous fumarate 200 mg d.d. for the first 4 weeks. Then, depending on their iron status, 100 mg d.d. for the following 12 weeks or 4 more weeks 200 mg d.d. followed by 4 weeks 100 mg d.d.. If iron levels are still too low after 12 weeks, the intervention has failed.
MonoFerDrug
Also called Ferinject, Cosmofer, Venofer
Study patients will be treated with intravenous iron. The brand name of the iv iron is dependent on the hospital policy and the doses will be according to recommended guidelines (weight of patient). Iv iron is intramural medication without add-on status and needs infusion at daycare.
| Study group | Role | What they receive |
|---|---|---|
| Oral iron | Active comparator | Ferrous fumarate 200mg daily for 4 weeks.
Group A1 (Normal Hb at week 4):
Ferrous fumarate 100mg daily for 12 weeks
Group A2 (Abnormal Hb at week 4):
Ferrous fumarate 200mg daily for 8 weeks
Group A2 at week 12:
Normal Hb: ferrous fumarate 100 mg daily till week 16 Abnormal Hb: intervention failure. End of study. Receives: Drug: Ferrous fumarate |
| IV Iron | Active comparator | Dosage based on iron formulation and instructions according to recommended guidelines (weight of patient) Receives: Drug: MonoFer |
What is being measured
The primary outcome is the main question the study is designed to answer.
Normalization of Hb concentration (> 7.3 mmol/L (females) or > 8.0 mmol/L (males)) from baseline to week 12 in both oral and iv iron supplementation group.
Percentage of patients who achieved an adequate hematologic response (defined by Hb > 7.3 mmol/L (females) or > 8.0 mmol/L (males)) after 12 weeks
Measured: After 12 weeks
Secondary outcomes (13)
Change in Hb levels
Change in Hb levels from baseline to weeks 4, 12, and 16 in both both oral and iv iron supplementation group.
Measured: baseline, weeks 4, 12 and 16
percentage of participants with ferritin levels > 100 microg/l
Percentage of patients who achieve ferritin levels > 100 microg/l in both both oral and iv iron supplementation group.
Measured: after 4, 12 and 16 weeks
Preference of patient for oral versus i.v. iron
percentage of patients who prefer oral or i.v. iron supplementation
Measured: at baseline and at week 16
Change in Disease-specific Quality of life (IBDQ)
Change in health related quality of life (measured by the sIBDQ) measuring physical, social, and emotional status (score 10-70, poor to good HRQoL) from baseline to week 16 in both both oral and iv iron supplementation group.
Measured: at week 16 in comparison with baseline
Change in overall/generic Quality of life (EQ-5D-5L)
Change in overall/generic quality of life from baseline to week 16 in both oral and iv iron supplementation group. This is measured by the EQ-5D-5L generating a 5-digit number that describes the patient's health state and a VAS that can be used as a quantitative measure of health outcome that reflect the patient's own judgement.
Measured: at week 16 in comparison with baseline
Change in productivity cost (iPCQ)
Change in productivity cost (measured by the iPCQ) from baseline to week 16 in both both oral and iv iron supplementation group. To calculate the cost of productivity losses, volumes are multiplied by unit cost prices.
Measured: at baseline and week 16
Change in medical consumption use (iMCQ)
Change in medical consumption use (measured by the iMCQ) from baseline to week 16 in both both oral and iv iron supplementation group. The costs of medical consumption are calculated by multiplying measured volumes of care by the cost per unit of care.
Measured: at baseline and week 16
Therapy adherence measured with the modified MMAS-8 for patients in the oral iron group
Therapy adherence measured with the modified MMAS-8 for patients in the oral iron group. Scores of 8 points, <8 to >6 points and ≤6 points are considered to have high, medium and low adherence, respectively.
Measured: at week 4, 8, 12 and at week 16 if patients still use iron according to the protocol
Correlation between response to iron therapy and disease activity
he correlation of disease activity (evaluated by fecal calprotectin levels and c-reactive protein levels) and response to iron therapy in both oral and iv iron supplementation group.
Measured: At week 4, 12 and 16
Incidence of hypophosphatemia during iron therapy
Percentage of patients who experienced hypophosphatemia throughout iron therapy in both oral and iv iron supplementation group.
Measured: At week 4, 12 and 16
Number of (serious) adverse events and adverse reactions according to MedDRA criteria.
Number of (serious) adverse events and adverse reactions according to MedDRA criteria throughout the study period.
Measured: From baseline until week 16
Change in clinical disease activity
Change in clinical disease activity (measured by mobile Health Index (mHI) 0-24 for patients with Crohn's disease and 0-34 for patients with ulcerative colitis; higher scores indicate a more active disease) 16 in both oral and iv iron supplementation group from baseline to week 16.
Measured: baseline, weeks 4, 12 and 16
Hepcidin - and soluble Transferrin Receptor (sTfR) - fecal calprotectin / CRP ratio
Measured: at baseline and week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2022
- Study start2 Jun 2022
- Primary completionMay 2025 (estimated)
- Study completionMay 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Inflammatory Bowel DiseasesStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 152 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University Medical Center Groningen, UMC Utrecht, Rijnstate Hospital, Erasmus Medical Center, Sint Franciscus Gasthuis, Adrz, Goes, Medical Center Haaglanden
- Responsible party
- Principal investigator, Andrea E. van der Meulen - de Jong, MD, PhD, Leiden University Medical Center
- Investigators
- A.E. van der Meulen - de Jong, MD, PhD, Principal investigator, Leiden University Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05581420
- Sponsor's protocol ID
- NL79363.058.21
- Acronym
- OVI-IBD
- Status last verified
- Oct 2022
- First submitted
- 17 Aug 2022
- Last updated
- 14 Oct 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Koppelman LJM, Loveikyte R, Goetgebuer RL, van der Marel S, de Vries AC, Dijkstra G, van der Meulen-de Jong AE; Dutch Iron Study Group. Clinical Trial: Predicting Response to Iron Therapy in Patients With Active Inflammatory Bowel Disease Using Hepcidin and Functional Iron Indices: A Multicentre Randomised Trial. Aliment Pharmacol Ther. 2026 Jul;64(2):166-176. doi: 10.1111/apt.70775. Epub 2026 Jun 8.
PubMed 42261111
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oral Versus Intravenous Iron in IBD Patients With Anti-inflammatory Therapy
- ClinicalTrials.gov ID
- NCT05581420
- Acronym / sponsor ID
- OVI-IBD / NL79363.058.21
- Conditions
- Inflammatory Bowel Diseases
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 152 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- University Medical Center Groningen, UMC Utrecht, Rijnstate Hospital, Erasmus Medical Center, Sint Franciscus Gasthuis, Adrz, Goes, Medical Center Haaglanden
- Study start
- 2 Jun 2022 (actual)
- Primary completion
- May 2025 (estimated)
- Study completion
- May 2025 (estimated)
- First posted
- 14 Oct 2022 (actual)
- 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.
Rationale: Iron deficiency anemia is the most common systemic manifestation of Inflammatory Bowel Diseases (IBD)-Crohn's disease and ulcerative colitis. Iron deficiency with or without anemia poses a diagnostic and therapeutic challenge due to chronic gastrointestinal blood loss and the inflammatory nature of IBD. Oral iron supplementation in active disease states is controversial. Hepcidin levels can be considered as the sum effect of all regulatory processes. Studies suggested that iron stores and hypoxia reduce hepcidin levels even in an inflammatory state. This is also reflected by a study which demonstrated low levels of hepcidin in patients with ferritin levels under 30μg/ml, regardless of disease activity or type. Furthermore, studies show that immunosuppressive medication decrease the level of hepcidin. This raises the question: is oral iron a viable alternative for patients under immunosuppressive treatment for active IBD? Objective: The hypothesis is that patients with mild to moderate IBD activity on immunosuppressive medication, show the same level of Hb increase after 12 weeks after either oral or iv iron supplementation, while the price of oral iron supplementation is significantly lower.
Detailed description
Study design: multicenter, prospective randomized non-inferiority study. Study population: Patients with inflammatory bowel disease on immunosuppressive medication with iron deficiency anemia, with increased inflammation parameters, but without an elevated ferritin (<100 μg/L).
Intervention: 152 patients will be randomized to a treatment group with either low dose oral iron or iv iron supplementation.
Main study endpoints: Normalization of Hb concentration (> 7.3 mmol/L (females) or > 8.0 mmol/L (males)) from baseline to week 12 in both oral and iv iron supplementation group.
Patients will receive either oral or intravenous iron therapy. Both therapies will be given according to existing guidelines. Participation to this trial will not increase the frequency of regular follow-up visits for patients. Blood for study measurements will be drawn simultaneously as blood for standard care tests. In addition, three questionnaires will be sent out regarding the patient's quality of life, disease activity, and productivity impairment. Iron therapy and biomaterial acquisition do not increase patients' risk because patients would have to undergo the same tests for standard IBD-care and receive iron therapy outside of the study. The study will be directly beneficial to participating patients because patients will undergo treatment for iron deficiency. The findings might help to develop guidelines for personalized iron therapy in the IBD population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral iron | Active comparator | Drug: Ferrous fumarateFerrous fumarate 200mg daily for 4 weeks. Group A1 (Normal Hb at week 4): Ferrous fumarate 100mg daily for 12 weeks Group A2 (Abnormal Hb at week 4): Ferrous fumarate 200mg daily for 8 weeks Group A2 at week 12: Normal Hb: ferrous fumarate 100 mg daily till week 16 Abnormal Hb: intervention failure. End of study. |
| IV Iron | Active comparator | Drug: MonoFerDosage based on iron formulation and instructions according to recommended guidelines (weight of patient) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Established IBD diagnosis (Crohn's disease, ulcerative colitis, IBD-unclassified)
- Adults (≥18 years of age)
- Any single Hb level between 6,2 - 7,3 mmol/L (females) 6,2 - 8,0 mmol/L (males)
- Any single ferritin <100 μg/L and transferrin saturation <20% within 4 weeks of study inclusion
- CRP > 5 mg/L and / or fecal calprotectin > 150 within 4 weeks of randomization
Key exclusion criteria (14 listed)
- Anemia due to reasons other than iron deficiency or chronic disease (e.g. hemoglobinopathy).
- Severe disease with a PGA score of 3
- IBD patients with a location of IBD at other places than ileum and / or colon (according to treating physician)
- Patients who are prescribed PPI
- Earlier significant side effect of oral iron or iv iron
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 |
|---|---|---|
| Ferrous fumaratePatients randomized in the oral group, will all be prescribed ferrous fumarate 200 mg d.d. for the first 4 weeks. Then, depending on their iron status, 100 mg d.d. for the following 12 weeks or 4 more weeks 200 mg d.d. followed by 4 weeks 100 mg d.d.. If iron levels are still too low after 12 weeks, the intervention has failed. | Drug | Oral iron |
| MonoFerAlso: Ferinject, Cosmofer, VenoferStudy patients will be treated with intravenous iron. The brand name of the iv iron is dependent on the hospital policy and the doses will be according to recommended guidelines (weight of patient). Iv iron is intramural medication without add-on status and needs infusion at daycare. | Drug | IV Iron |
Primary outcome
Normalization of Hb concentration (> 7.3 mmol/L (females) or > 8.0 mmol/L (males)) from baseline to week 12 in both oral and iv iron supplementation group.
Time frame: After 12 weeks
Percentage of patients who achieved an adequate hematologic response (defined by Hb > 7.3 mmol/L (females) or > 8.0 mmol/L (males)) after 12 weeks
13 secondary outcomes
Change in Hb levels
Time frame: baseline, weeks 4, 12 and 16
percentage of participants with ferritin levels > 100 microg/l
Time frame: after 4, 12 and 16 weeks
Preference of patient for oral versus i.v. iron
Time frame: at baseline and at week 16
Change in Disease-specific Quality of life (IBDQ)
Time frame: at week 16 in comparison with baseline
Change in overall/generic Quality of life (EQ-5D-5L)
Time frame: at week 16 in comparison with baseline
Change in productivity cost (iPCQ)
Time frame: at baseline and week 16
Change in medical consumption use (iMCQ)
Time frame: at baseline and week 16
Therapy adherence measured with the modified MMAS-8 for patients in the oral iron group
Time frame: at week 4, 8, 12 and at week 16 if patients still use iron according to the protocol
Correlation between response to iron therapy and disease activity
Time frame: At week 4, 12 and 16
Incidence of hypophosphatemia during iron therapy
Time frame: At week 4, 12 and 16
Number of (serious) adverse events and adverse reactions according to MedDRA criteria.
Time frame: From baseline until week 16
Change in clinical disease activity
Time frame: baseline, weeks 4, 12 and 16
Hepcidin - and soluble Transferrin Receptor (sTfR) - fecal calprotectin / CRP ratio
Time frame: at baseline and week 12
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2022.
- Derived from this study: PubMed 42261111Koppelman LJM, Loveikyte R, Goetgebuer RL, van der Marel S, de Vries AC, Dijkstra G, van der Meulen-de Jong AE; Dutch Iron Study Group. Clinical Trial: Predicting Response to Iron Therapy in Patients With Active Inflammatory Bowel Disease Using Hepcidin and Functional Iron Indices: A Multicentre Randomised Trial. Aliment Pharmacol Ther. 2026 Jul;64(2):166-176. doi: 10.1111/apt.70775. Epub 2026 Jun 8.
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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.
A.E. van der Meulen - de Jong, MD, PhD principal investigator
Leiden University Medical Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ferrous fumarate and MonoFer in people with Inflammatory Bowel Diseases, run by Leiden University Medical Center at 1 site in Netherlands.
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 8 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 14 Oct 2022. 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 Netherlands. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact L.J.M. Koppelman, Msc. (0031715297902, patientenibd@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Normalization of Hb concentration (> 7.3 mmol/L (females) or > 8.0 mmol/L (males)) from baseline to week 12 in both oral and iv iron supplementation group. (time frame: After 12 weeks). 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 NCT05581420, which also lists 1 linked publication.
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 14 Oct 2022.