Inflammatory Bowel DiseasePhase 3CAESARNCT06321887
EffiCacy and sAfEty of Low doSe orAl iRon for Anaemia in IBD
A Phase 3 study testing Ferrous fumarate syrup 2.5ml/70mg (22.5mg elemental iron), Ferrous fumarate syrup 2.5ml/70mg(45mg elemental iron) and Ferrous fumarate syrup 2.5ml/70mg (90mg elemental iron) in people with Inflammatory Bowel Disease and Iron Deficiency Anemia, run by Liverpool University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Iron deficiency anaemia (IDA) is common in inflammatory bowel disease (IBD). However, although iron is commonly prescribed, the amount of elemental iron needed to achieve clinical efficacy, and the optimal method of supplementation, are under debate. Read more about this study
- Who is it for?
- Ages 18 to 79 yearsHealthy volunteers can take part
- Conditions the study is for
- Inflammatory Bowel Disease, Iron Deficiency Anemia
- What is being tested?
- Ferrous fumarate syrup 2.5ml/70mg (22.5mg elemental iron), Ferrous fumarate syrup 2.5ml/70mg(45mg elemental iron) and Ferrous fumarate syrup 2.5ml/70mg (90mg elemental iron)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 20 Oct 2023to 1 Oct 2025
- Phase
- Phase 3
- 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 to 79 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patient is willing to participate in the study and has signed the informed consent.
- Patients aged 18-80 years.
- Patients diagnosed with Crohn's disease or ulcerative colitis diagnosed by conventional clinical, radiological and histological criteria.
- Remission or active disease.
- Haemoglobin level 7-13 g/dL men, 7-12 g/dL women and ferritin <30, normal B12 and folate (or ferritin <100 but iron sats <16 in the presence of inflammation defined as CRP>5mg/L, faecal calprotectin>250 microgram/g and presence of endoscopic inflammation).
Who cannot join
- Patients under 18 or unable to give informed consent.
- Patients with advanced liver disease.
- Patients with advanced renal disease with eGFR<45ml/min
- Previous intolerance to even low doses of oral iron
- Patients with severe cardiovascular disease defined as previous unstable angina and or previous MI without intervention.
- Participation in other trials in the last 3 months.
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- Serious inter-current infection or other clinically important active disease (including renal and hepatic disease) and recently diagnosed gastrointestinal tract cancers
- Pregnant, post-partum (<3months) or breast feeding females
- Erythropoietin therapy.
- Recent blood transfusion within 30 days.
- Recent iron infusion within 30 days.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Liverpool University Foundation NHS Trust
Liverpool
S Subramanian, 01517062000, RGT@liverpoolft.nhs.uk
T Conley, 01517062000, RGT@liverpoolft.nhs.uk
About this study
Official title: A Pilot Study to Assess the Efficacy and Tolerability of Reduced Dose Oral Iron in the Treatment of Iron Deficiency Anaemia in Inflammatory Bowel Disease Patients.
Iron deficiency anaemia (IDA) is common in inflammatory bowel disease (IBD). However, although iron is commonly prescribed, the amount of elemental iron needed to achieve clinical efficacy, and the optimal method of supplementation, are under debate. This pilot study aims to investigate the efficacy and safety of low dose and standard dose oral iron preparations for the treatment of IDA in patients with IBD.
Read the detailed description
BACKGROUND:
Anaemia, particularly iron-deficiency anaemia, is a common complication of inflammatory bowel disease (IBD). The prevalence of anaemia (6-74%) and iron deficiency (36-90%) varies widely among reported studies. The predominant cause of iron deficiency in IBD is intestinal blood loss but other factors such as malabsorption and reduced intake may also play a role. Thus, the need for iron supplementation is an often encountered clinical problem in IBD. Although iron is commonly prescribed, the amount of elemental iron needed to achieve clinical efficacy, and the optimal method of supplementation, are under debate. As intravenous (IV) iron supplementation has become safer, calls for increased utilization have appeared. However, there are significant cost implications to using IV iron. On average, a 1-month supply of oral ferrous sulfate costs $12, in comparison with approximately $600-$700 for a treatment cycle of (IV) iron sucrose, excluding the cost of IV administration.
Overall, the comparative studies of IV vs. oral iron do not demonstrate a significant difference in haemoglobin repletion favouring IV iron therapy. Haemoglobin concentrations were similar at the end of treatment in all studies. A single study suggested a superiority for IV iron with a haemoglobin increase greater than 2 g/dl in 47% of the patients on oral iron compared with 66% on IV iron (P = 0.07). However, this could be accounted for by a high withdrawal rate (24%) in the oral iron group. In the largest comparative study, of 196 subjects, median haemoglobin improved similarly, from 8.7 to 12.3 g/dl in the IV group and from 9.1 to 12.1 g/dl in the ferrous sulfate group (P = 0.70). Thus, intravenous iron appears no more effective than oral iron in repletion of iron status as the rate-limiting step appears to be synthesis of red cells, which is not accelerated by IV iron delivery.
The main reason behind the preference of IV iron over oral iron is based on the concern that oral iron may exacerbate IBD. An often-cited study investigating whether oral iron worsens IBD in comparison with IV iron assessed disease activity in 19 IBD patients, 11 with CD and 8 with UC, randomized to either oral ferrous fumarate or IV iron sucrose over a 14-day period. Although the authors argued that disease activity was worsened by oral iron therapy, their use of numerous unconventional assessments weakens this conclusion. The trial was done as a crossover study with a minimum 6-week washout period, so the previous drug therapy may have affected the results. The number of subjects with IBD was small (N = 19). The authors created a synthesized overall disease activity score by combining UC and CD scales and also reported on subscales within activity indexes to identify significant differences. When the two groups were compared, however, there was no statistically significant difference in the overall synthesized disease activity score.
Another factor associated with intolerance of oral iron may be related to the dose of elemental iron administered. In order to maintain iron balance, adult men need to absorb 1-1.5 mg/d, menstruating women need 1-3 mg/d, and pregnant women need approximately 4-5 mg/d. Based on this, the recommended daily allowance of elemental iron is about 8 mg in adult men and postmenopausal women, 18 mg in premenopausal women, and 27 mg in pregnant women. However, most studies investigating the efficacy of oral iron have used a typical dose of 150-200mg/d of elemental iron, 10-20 fold in excess of the recommended daily allowance. Because of the 20% incidence level of intolerance at these conventional doses of elemental iron, recent studies have investigated the efficacy and side effects associated with low-dose oral iron supplementation. A study in the elderly (age >80) randomised 90 patients with iron-deficiency anaemia to 15, 50, or 150 mg of daily oral elemental iron over 2 months. All three dosage groups experienced a similar, statistically significant increase in haemoglobin after 2 months. These studies have not been done in IBD.
This pilot study aims to investigate the efficacy and safety of low dose and standard dose oral iron preparations.
HYPOTHESIS:
Low dose oral iron is effective and safe in the treatment of iron deficiency anaemia in inflammatory bowel disease.
- Conditions
- Inflammatory Bowel Disease, Iron Deficiency Anemia
- Being tested
- Ferrous fumarate syrup 2.5ml/70mg (22.5mg elemental iron), Ferrous fumarate syrup 2.5ml/70mg(45mg elemental iron), Ferrous fumarate syrup 2.5ml/70mg (90mg elemental iron)
- Medical subject headings
- Inflammatory Bowel Diseases, Anemia, Iron-Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ferrous fumarate syrup 2.5ml/70mg (22.5mg elemental iron)Drug
Ferrous fumarate syrup 2.5ml/70mg (22.5mg elemental iron) daily for 8 weeks (N=10).
Ferrous fumarate syrup 2.5ml/70mg(45mg elemental iron)Drug
Ferrous fumarate syrup 5ml/140mg (45mg elemental iron) daily for 8 weeks (N=10).
Ferrous fumarate syrup 2.5ml/70mg (90mg elemental iron)Drug
Ferrous fumarate syrup 5ml/140mg twice daily (90mg elemental iron) for 8 weeks (N=10).
| Study group | Role | What they receive |
|---|---|---|
| STAGE 1 | Experimental | The first stage shall recruit 10 patients and is used to assess the incidence of oral iron related toxicity.
Patients will be prescribed:
• Ferrous fumarate syrup 2.5ml/70mg (22.5mg elemental iron) daily for 8 weeks.
If patients experience toxicity (defined as symptoms not tolerated by the patient), the trial medication would be stopped and IV Iron treatment given.
If toxicity occurs in 2 or more patients where we have to stop treatment, we will continue to recruit 30 patients only to the Ferrous fumarate syrup 2.5ml/70mg (22.5mg elemental iron) daily for 8 weeks. If the toxicity is acceptable and the Hb improves, we will continue to recruit to 22.5mg oral iron/day.
If the toxicity is acceptable but there is no improvement in haemoglobin the next patients will be recruited to stage 2. Receives: Drug: Ferrous fumarate syrup 2.5ml/70mg (22.5mg elemental iron) |
| STAGE 2 | Experimental | Ten subjects each will then be sequentially assigned to one of the following groups:
* Ferrous fumarate syrup 5ml/140mg (45mg elemental iron) daily for 8 weeks.
* Ferrous fumarate syrup 5ml/140mg twice daily (90mg elemental iron) for 8 weeks.
If 2 or more patients experience toxicity at Ferrous fumarate syrup 5ml/140mg (45mg elemental iron) or Ferrous fumarate syrup 5ml/140mg twice daily (90mg elemental iron) we will reduce the dose to the previous level of Ferrous fumarate syrup 2.5ml/70mg (22.5mg elemental iron) and continue to recruit.
30 patients shall be used to estimate the change in haemoglobin between baseline and the final analysis point.
If no dose reduction is required, only the last 20 patients shall be used to assess haemoglobin.
The overall endpoint is the haemoglobin level. Receives: Drug: Ferrous fumarate syrup 2.5ml/70mg(45mg elemental iron); Drug: Ferrous fumarate syrup 2.5ml/70mg (90mg elemental iron) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in haemoglobin concentration from baseline to week 8.
Measured using serum haemoglobin concentration measured in g/L, taken at week 0 and week 8.
Measured: 8 weeks
Secondary outcomes (8)
Assessment of iron stores at baseline and week 8
Measured using serum ferritin values measured in ug/L taken at week 0 and week 8.
Measured: 8 weeks
Assessment of faecal calprotectin at baseline and week 8
Measures on a continuous numeric scale ranging from 21ug/g to 2099ugug. Values outside these thresholds reported as <20ug/g to >2100ug/g.
Measured: 8 weeks
Assessment of IBD severity. For ulcerative colitis this will be done using simple colitis clinical activity index (SCCAI). Values calculated at week 0 and week 8.
SCCAI measured from 0-19 on a continuous numeric scale.
Measured: 8 weeks
Assessment of IBD severity. For Crohn's disease (or IBD-unclassified) the Harvey Bradshaw Index (HBI) will be used. Values calculated at week 0 and week 8.
HBI measured from 0-28 on a continuous numeric scale.
Measured: 8 weeks
Assessment of quality of life using the IBD-QUK score at baseline and week 8
IBD-QUK measured from 0-96 on a continuous numeric scale, then expressed as a percentage from 0-100%.
Measured: 8 weeks
Assessment of patient global assessment of symptom severity by visual analogue score at baseline and week 8.
A series of eight questions, each comprising a score. The higher the sum of scores, the more severe the symptom profile. Question one pertains to bowel frequency (total number of stools per week), questions two through eight refer to specific gastrointestinal complaints, the severity of which are scored by placing a marker on a 10cm visual scale - the total length of the line marked denotes the severity score for each question.
Measured: 8 weeks
Assessment of fatigue at baseline and week 8 using IBD-F fatigue score
Scored using a series of 35 questions, each scored from 0 to 4. The higher the total score (out of a possible total of 140), the higher the severity of fatigue.
Measured: 8 weeks
Assessment of possible drug-related side effects: nausea, diarrhoea, mood disturbance, sleep disturbance - will all be assessed at baseline and week 8.
Measured using a binary outcome (yes/no) measure when asked whether any of the aforementioned symptoms have been experienced by the participant during the study period.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2024
- Study start20 Oct 2023
- Primary completion1 Oct 2024 (estimated)
- Study completion1 Oct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Inflammatory Bowel DiseaseStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- This is an adaptive, open label study to compare the efficacy and tolerability of 8 weeks of low dose oral iron, in the treatment of iron deficiency anaemia in patients with inflammatory bowel disease (IBD).
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Liverpool University Hospitals NHS Foundation Trust
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- T Conley, Principal investigator, Liverpool University Foundation NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06321887
- Sponsor's protocol ID
- 5155
- Acronym
- CAESAR
- Status last verified
- Feb 2024
- First submitted
- 14 Feb 2024
- Last updated
- 20 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Kulnigg S, Gasche C. Systematic review: managing anaemia in Crohn's disease. Aliment Pharmacol Ther. 2006 Dec;24(11-12):1507-23. doi: 10.1111/j.1365-2036.2006.03146.x.
PubMed 17206940Gasche C, Berstad A, Befrits R, Beglinger C, Dignass A, Erichsen K, Gomollon F, Hjortswang H, Koutroubakis I, Kulnigg S, Oldenburg B, Rampton D, Schroeder O, Stein J, Travis S, Van Assche G. Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel diseases. Inflamm Bowel Dis. 2007 Dec;13(12):1545-53. doi: 10.1002/ibd.20285.
PubMed 17985376Hodges P, Gee M, Grace M, Thomson AB. Vitamin and iron intake in patients with Crohn's disease. J Am Diet Assoc. 1984 Jan;84(1):52-8.
PubMed 6690565Gisbert JP, Gomollon F. Common misconceptions in the diagnosis and management of anemia in inflammatory bowel disease. Am J Gastroenterol. 2008 May;103(5):1299-307. doi: 10.1111/j.1572-0241.2008.01846.x.
PubMed 18477354Stein J, Hartmann F, Dignass AU. Diagnosis and management of iron deficiency anemia in patients with IBD. Nat Rev Gastroenterol Hepatol. 2010 Nov;7(11):599-610. doi: 10.1038/nrgastro.2010.151. Epub 2010 Oct 5.
PubMed 20924367Schroder O, Mickisch O, Seidler U, de Weerth A, Dignass AU, Herfarth H, Reinshagen M, Schreiber S, Junge U, Schrott M, Stein J. Intravenous iron sucrose versus oral iron supplementation for the treatment of iron deficiency anemia in patients with inflammatory bowel disease--a randomized, controlled, open-label, multicenter study. Am J Gastroenterol. 2005 Nov;100(11):2503-9. doi: 10.1111/j.1572-0241.2005.00250.x.
PubMed 16279906Erichsen K, Ulvik RJ, Nysaeter G, Johansen J, Ostborg J, Berstad A, Berge RK, Hausken T. Oral ferrous fumarate or intravenous iron sucrose for patients with inflammatory bowel disease. Scand J Gastroenterol. 2005 Sep;40(9):1058-65. doi: 10.1080/00365520510023198.
PubMed 16165718Kulnigg S, Stoinov S, Simanenkov V, Dudar LV, Karnafel W, Garcia LC, Sambuelli AM, D'Haens G, Gasche C. A novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT) randomized controlled trial. Am J Gastroenterol. 2008 May;103(5):1182-92. doi: 10.1111/j.1572-0241.2007.01744.x. Epub 2008 Mar 26.
PubMed 18371137Lindgren S, Wikman O, Befrits R, Blom H, Eriksson A, Granno C, Ung KA, Hjortswang H, Lindgren A, Unge P. Intravenous iron sucrose is superior to oral iron sulphate for correcting anaemia and restoring iron stores in IBD patients: A randomized, controlled, evaluator-blind, multicentre study. Scand J Gastroenterol. 2009;44(7):838-45. doi: 10.1080/00365520902839667.
PubMed 19330567Munoz M, Villar I, Garcia-Erce JA. An update on iron physiology. World J Gastroenterol. 2009 Oct 7;15(37):4617-26. doi: 10.3748/wjg.15.4617.
PubMed 19787824Hallberg L, Ryttinger L, Solvell L. Side-effects of oral iron therapy. A double-blind study of different iron compounds in tablet form. Acta Med Scand Suppl. 1966;459:3-10. doi: 10.1111/j.0954-6820.1966.tb19403.x. No abstract available.
PubMed 5957969
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Assess the Efficacy and Tolerability of Reduced Dose Oral Iron in the Treatment of Iron Deficiency Anaemia in Inflammatory Bowel Disease Patients.
- ClinicalTrials.gov ID
- NCT06321887
- Acronym / sponsor ID
- CAESAR / 5155
- Conditions
- Inflammatory Bowel Disease, Iron Deficiency Anemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Liverpool University Hospitals NHS Foundation TrustOther government
- Study start
- 20 Oct 2023 (actual)
- Primary completion
- 1 Oct 2024 (estimated)
- Study completion
- 1 Oct 2025 (estimated)
- First posted
- 20 Mar 2024 (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.
Iron deficiency anaemia (IDA) is common in inflammatory bowel disease (IBD). However, although iron is commonly prescribed, the amount of elemental iron needed to achieve clinical efficacy, and the optimal method of supplementation, are under debate. This pilot study aims to investigate the efficacy and safety of low dose and standard dose oral iron preparations for the treatment of IDA in patients with IBD.
Detailed description
BACKGROUND:
Anaemia, particularly iron-deficiency anaemia, is a common complication of inflammatory bowel disease (IBD). The prevalence of anaemia (6-74%) and iron deficiency (36-90%) varies widely among reported studies. The predominant cause of iron deficiency in IBD is intestinal blood loss but other factors such as malabsorption and reduced intake may also play a role. Thus, the need for iron supplementation is an often encountered clinical problem in IBD. Although iron is commonly prescribed, the amount of elemental iron needed to achieve clinical efficacy, and the optimal method of supplementation, are under debate. As intravenous (IV) iron supplementation has become safer, calls for increased utilization have appeared. However, there are significant cost implications to using IV iron. On average, a 1-month supply of oral ferrous sulfate costs $12, in comparison with approximately $600-$700 for a treatment cycle of (IV) iron sucrose, excluding the cost of IV administration.
Overall, the comparative studies of IV vs. oral iron do not demonstrate a significant difference in haemoglobin repletion favouring IV iron therapy. Haemoglobin concentrations were similar at the end of treatment in all studies. A single study suggested a superiority for IV iron with a haemoglobin increase greater than 2 g/dl in 47% of the patients on oral iron compared with 66% on IV iron (P = 0.07). However, this could be accounted for by a high withdrawal rate (24%) in the oral iron group. In the largest comparative study, of 196 subjects, median haemoglobin improved similarly, from 8.7 to 12.3 g/dl in the IV group and from 9.1 to 12.1 g/dl in the ferrous sulfate group (P = 0.70). Thus, intravenous iron appears no more effective than oral iron in repletion of iron status as the rate-limiting step appears to be synthesis of red cells, which is not accelerated by IV iron delivery.
The main reason behind the preference of IV iron over oral iron is based on the concern that oral iron may exacerbate IBD. An often-cited study investigating whether oral iron worsens IBD in comparison with IV iron assessed disease activity in 19 IBD patients, 11 with CD and 8 with UC, randomized to either oral ferrous fumarate or IV iron sucrose over a 14-day period. Although the authors argued that disease activity was worsened by oral iron therapy, their use of numerous unconventional assessments weakens this conclusion. The trial was done as a crossover study with a minimum 6-week washout period, so the previous drug therapy may have affected the results. The number of subjects with IBD was small (N = 19). The authors created a synthesized overall disease activity score by combining UC and CD scales and also reported on subscales within activity indexes to identify significant differences. When the two groups were compared, however, there was no statistically significant difference in the overall synthesized disease activity score.
Another factor associated with intolerance of oral iron may be related to the dose of elemental iron administered. In order to maintain iron balance, adult men need to absorb 1-1.5 mg/d, menstruating women need 1-3 mg/d, and pregnant women need approximately 4-5 mg/d. Based on this, the recommended daily allowance of elemental iron is about 8 mg in adult men and postmenopausal women, 18 mg in premenopausal women, and 27 mg in pregnant women. However, most studies investigating the efficacy of oral iron have used a typical dose of 150-200mg/d of elemental iron, 10-20 fold in excess of the recommended daily allowance. Because of the 20% incidence level of intolerance at these conventional doses of elemental iron, recent studies have investigated the efficacy and side effects associated with low-dose oral iron supplementation. A study in the elderly (age >80) randomised 90 patients with iron-deficiency anaemia to 15, 50, or 150 mg of daily oral elemental iron over 2 months. All three dosage groups experienced a similar, statistically significant increase in haemoglobin after 2 months. These studies have not been done in IBD.
This pilot study aims to investigate the efficacy and safety of low dose and standard dose oral iron preparations.
HYPOTHESIS:
Low dose oral iron is effective and safe in the treatment of iron deficiency anaemia in inflammatory bowel disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is an adaptive, open label study to compare the efficacy and tolerability of 8 weeks of low dose oral iron, in the treatment of iron deficiency anaemia in patients with inflammatory bowel disease (IBD).
| Arm | Type | Receives |
|---|---|---|
| STAGE 1 | Experimental | Drug: Ferrous fumarate syrup 2.5ml/70mg (22.5mg elemental iron)The first stage shall recruit 10 patients and is used to assess the incidence of oral iron related toxicity. Patients will be prescribed: • Ferrous fumarate syrup 2.5ml/70mg (22.5mg elemental iron) daily for 8 weeks. If patients experience toxicity (defined as symptoms not tolerated by the patient), the trial medication would be stopped and IV Iron treatment given. If toxicity occurs in 2 or more patients where we have to stop treatment, we will continue to recruit 30 patients only to the Ferrous fumarate syrup 2.5ml/70mg (22.5mg elemental iron) daily for 8 weeks. If the toxicity is acceptable and the Hb improves, we will continue to recruit to 22.5mg oral iron/day. If the toxicity is acceptable but there is no improvement in haemoglobin the next patients will be recruited to stage 2. |
| STAGE 2 | Experimental | Drug: Ferrous fumarate syrup 2.5ml/70mg(45mg elemental iron), Drug: Ferrous fumarate syrup 2.5ml/70mg (90mg elemental iron)Ten subjects each will then be sequentially assigned to one of the following groups: * Ferrous fumarate syrup 5ml/140mg (45mg elemental iron) daily for 8 weeks. * Ferrous fumarate syrup 5ml/140mg twice daily (90mg elemental iron) for 8 weeks. If 2 or more patients experience toxicity at Ferrous fumarate syrup 5ml/140mg (45mg elemental iron) or Ferrous fumarate syrup 5ml/140mg twice daily (90mg elemental iron) we will reduce the dose to the previous level of Ferrous fumarate syrup 2.5ml/70mg (22.5mg elemental iron) and continue to recruit. 30 patients shall be used to estimate the change in haemoglobin between baseline and the final analysis point. If no dose reduction is required, only the last 20 patients shall be used to assess haemoglobin. The overall endpoint is the haemoglobin level. |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patient is willing to participate in the study and has signed the informed consent.
- Patients aged 18-80 years.
- Patients diagnosed with Crohn's disease or ulcerative colitis diagnosed by conventional clinical, radiological and histological criteria.
- Remission or active disease.
- Haemoglobin level 7-13 g/dL men, 7-12 g/dL women and ferritin <30, normal B12 and folate (or ferritin <100 but iron sats <16 in the presence of inflammation defined as CRP>5mg/L, faecal calprotectin>250 microgram/g and presence of endoscopic inflammation).
Key exclusion criteria (11 listed)
- Patients under 18 or unable to give informed consent.
- Patients with advanced liver disease.
- Patients with advanced renal disease with eGFR<45ml/min
- Previous intolerance to even low doses of oral iron
- Patients with severe cardiovascular disease defined as previous unstable angina and or previous MI without intervention.
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 fumarate syrup 2.5ml/70mg (22.5mg elemental iron)Ferrous fumarate syrup 2.5ml/70mg (22.5mg elemental iron) daily for 8 weeks (N=10). | Drug | STAGE 1 |
| Ferrous fumarate syrup 2.5ml/70mg(45mg elemental iron)Ferrous fumarate syrup 5ml/140mg (45mg elemental iron) daily for 8 weeks (N=10). | Drug | STAGE 2 |
| Ferrous fumarate syrup 2.5ml/70mg (90mg elemental iron)Ferrous fumarate syrup 5ml/140mg twice daily (90mg elemental iron) for 8 weeks (N=10). | Drug | STAGE 2 |
Primary outcome
Change in haemoglobin concentration from baseline to week 8.
Time frame: 8 weeks
Measured using serum haemoglobin concentration measured in g/L, taken at week 0 and week 8.
8 secondary outcomes
Assessment of iron stores at baseline and week 8
Time frame: 8 weeks
Assessment of faecal calprotectin at baseline and week 8
Time frame: 8 weeks
Assessment of IBD severity. For ulcerative colitis this will be done using simple colitis clinical activity index (SCCAI). Values calculated at week 0 and week 8.
Time frame: 8 weeks
Assessment of IBD severity. For Crohn's disease (or IBD-unclassified) the Harvey Bradshaw Index (HBI) will be used. Values calculated at week 0 and week 8.
Time frame: 8 weeks
Assessment of quality of life using the IBD-QUK score at baseline and week 8
Time frame: 8 weeks
Assessment of patient global assessment of symptom severity by visual analogue score at baseline and week 8.
Time frame: 8 weeks
Assessment of fatigue at baseline and week 8 using IBD-F fatigue score
Time frame: 8 weeks
Assessment of possible drug-related side effects: nausea, diarrhoea, mood disturbance, sleep disturbance - will all be assessed at baseline and week 8.
Time frame: 8 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2024.
- Background: PubMed 17206940Kulnigg S, Gasche C. Systematic review: managing anaemia in Crohn's disease. Aliment Pharmacol Ther. 2006 Dec;24(11-12):1507-23. doi: 10.1111/j.1365-2036.2006.03146.x.
- Background: PubMed 17985376Gasche C, Berstad A, Befrits R, Beglinger C, Dignass A, Erichsen K, Gomollon F, Hjortswang H, Koutroubakis I, Kulnigg S, Oldenburg B, Rampton D, Schroeder O, Stein J, Travis S, Van Assche G. Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel diseases. Inflamm Bowel Dis. 2007 Dec;13(12):1545-53. doi: 10.1002/ibd.20285.
- Background: PubMed 6690565Hodges P, Gee M, Grace M, Thomson AB. Vitamin and iron intake in patients with Crohn's disease. J Am Diet Assoc. 1984 Jan;84(1):52-8.
- Background: PubMed 18477354Gisbert JP, Gomollon F. Common misconceptions in the diagnosis and management of anemia in inflammatory bowel disease. Am J Gastroenterol. 2008 May;103(5):1299-307. doi: 10.1111/j.1572-0241.2008.01846.x.
- Background: PubMed 20924367Stein J, Hartmann F, Dignass AU. Diagnosis and management of iron deficiency anemia in patients with IBD. Nat Rev Gastroenterol Hepatol. 2010 Nov;7(11):599-610. doi: 10.1038/nrgastro.2010.151. Epub 2010 Oct 5.
- Background: PubMed 16279906Schroder O, Mickisch O, Seidler U, de Weerth A, Dignass AU, Herfarth H, Reinshagen M, Schreiber S, Junge U, Schrott M, Stein J. Intravenous iron sucrose versus oral iron supplementation for the treatment of iron deficiency anemia in patients with inflammatory bowel disease--a randomized, controlled, open-label, multicenter study. Am J Gastroenterol. 2005 Nov;100(11):2503-9. doi: 10.1111/j.1572-0241.2005.00250.x.
- Background: PubMed 16165718Erichsen K, Ulvik RJ, Nysaeter G, Johansen J, Ostborg J, Berstad A, Berge RK, Hausken T. Oral ferrous fumarate or intravenous iron sucrose for patients with inflammatory bowel disease. Scand J Gastroenterol. 2005 Sep;40(9):1058-65. doi: 10.1080/00365520510023198.
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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.
T Conley principal investigator
Liverpool University Foundation NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ferrous fumarate syrup 2.5ml/70mg (22.5mg elemental iron), Ferrous fumarate syrup 2.5ml/70mg(45mg elemental iron) and Ferrous fumarate syrup 2.5ml/70mg (90mg elemental iron) in people with Inflammatory Bowel Disease and Iron Deficiency Anemia, run by Liverpool University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
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 5 inclusion and 11 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 20 Mar 2024. 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 United Kingdom. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 S Subramanian (01517062000, RGT@liverpoolft.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in haemoglobin concentration from baseline to week 8. (time frame: 8 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 NCT06321887, which also lists 11 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 20 Mar 2024.