Clinical trial NCT05581420: Oral Versus Intravenous Iron in IBD Patients With Anti-inflammatory Therapy.
Official title: Oral Versus Intravenous Iron in IBD Patients With Anti-inflammatory Therapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Inflammatory Bowel Diseases
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: University Medical Center Groningen
name: UMC Utrecht
name: Rijnstate Hospital
name: Erasmus Medical Center
name: Sint Franciscus Gasthuis
name: Adrz, Goes
name: Medical Center Haaglanden
First posted: 2022-10-14
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)
* 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

Primary outcomes:
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.
timeFrame: After 12 weeks
Secondary outcomes:
measure: Change in Hb levels
timeFrame: baseline, weeks 4, 12 and 16
measure: percentage of participants with ferritin levels > 100 microg/l
timeFrame: after 4, 12 and 16 weeks
measure: Preference of patient for oral versus i.v. iron
timeFrame: at baseline and at week 16
measure: Change in Disease-specific Quality of life (IBDQ)
timeFrame: at week 16 in comparison with baseline
measure: Change in overall/generic Quality of life (EQ-5D-5L)
timeFrame: at week 16 in comparison with baseline
measure: Change in productivity cost (iPCQ)
timeFrame: at baseline and week 16
measure: Change in medical consumption use (iMCQ)
timeFrame: at baseline and week 16
measure: Therapy adherence measured with the modified MMAS-8 for patients in the oral iron group
timeFrame: at week 4, 8, 12 and at week 16 if patients still use iron according to the protocol
measure: Correlation between response to iron therapy and disease activity
timeFrame: At week 4, 12 and 16
measure: Incidence of hypophosphatemia during iron therapy
timeFrame: At week 4, 12 and 16
measure: Number of (serious) adverse events and adverse reactions according to MedDRA criteria.
timeFrame: From baseline until week 16
measure: Change in clinical disease activity
timeFrame: baseline, weeks 4, 12 and 16
measure: Hepcidin - and soluble Transferrin Receptor (sTfR) - fecal calprotectin / CRP ratio
timeFrame: at baseline and week 12
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Centre
state: Zuid-Holland
Study officials:
affiliation: Leiden University Medical Centre
name: A.E. van der Meulen - de Jong, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: