EffiCacy and sAfEty of Low doSe orAl iRon for Anaemia in IBD

NCT06321887 | Recruiting Phase 3 DMC

• 1 other identifier: 5155
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Inflammatory Bowel Disease; Iron Deficiency Anemia

Outcome Measures

Primary Outcomes (1)

• 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.

  8 weeks

Secondary Outcomes (8)

• Assessment of iron stores at baseline and week 8

  8 weeks

• Assessment of faecal calprotectin at baseline and week 8

  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.

  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.

  8 weeks

• Assessment of quality of life using the IBD-QUK score at baseline and week 8

  8 weeks

Other Outcomes (2)

• Experimental arm 1: Assessment of faecal metabolome composition at baseline and week 8

  8 weeks

• Experimental arm 2: Assessment of faecal microbiota composition at baseline and week 8

  8 weeks

Study Arms (2)

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.

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.

Drug: Ferrous fumarate syrup 2.5ml/70mg(45mg elemental iron); Drug: Ferrous fumarate syrup 2.5ml/70mg (90mg elemental iron)

Interventions

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).

STAGE 1

Ferrous fumarate syrup 2.5ml/70mg(45mg elemental iron) DRUG

Ferrous fumarate syrup 5ml/140mg (45mg elemental iron) daily for 8 weeks (N=10).

STAGE 2

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).

STAGE 2

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Liverpool University Hospitals NHS Foundation Trust: lead

Study Sites (1)

Liverpool University Foundation NHS Trust

Liverpool, United Kingdom

RECRUITING

Related Publications (11)

• 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.

  PMID: 17206940 BACKGROUND

• Gasche 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.

  PMID: 17985376 BACKGROUND

• Hodges 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.

  PMID: 6690565 BACKGROUND

• Gisbert 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.

  PMID: 18477354 BACKGROUND

• Stein 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.

  PMID: 20924367 BACKGROUND

• Schroder 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.

  PMID: 16279906 BACKGROUND

• Erichsen 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.

  PMID: 16165718 BACKGROUND

• Kulnigg 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.

  PMID: 18371137 BACKGROUND

• Lindgren 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.

  PMID: 19330567 BACKGROUND

• Munoz 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.

  PMID: 19787824 BACKGROUND

• Hallberg 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.

  PMID: 5957969 BACKGROUND

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Anemia, Iron-Deficiency

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Anemia, Hypochromic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• T Conley

  Liverpool University Foundation NHS Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

S Subramanian

CONTACT

01517062000; RGT@liverpoolft.nhs.uk

T Conley

CONTACT

01517062000; RGT@liverpoolft.nhs.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: February 14, 2024
• First Posted: March 20, 2024
• Study Start: October 20, 2023
• Primary Completion: October 1, 2024
• Study Completion: October 1, 2025
• Last Updated: March 20, 2024

Record last verified: 2024-02

Locations

GB (1)