Clinical Burden of Anemia in Inflammatory Bowel Disease: Therapeutic Trial

NCT04587141 | Unknown Phase 3 DMC

• 1 other identifier: IRCCSPSM 2
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Anemia is the most common extraintestinal manifestation of inflammatory bowel diseases (IBD), Although most cases of anemia in IBD are due to iron deficiency, many patients with iron deficiency anemia (IDA) are not treated with iron supplementation. In addition, it has not been firmly established which iron supplementation modality provides the best results in terms of effectiveness and safety. In the present study the investigators will compare the effectiveness and efficacy of three iron supplementation modalities in IBD-associated IDA. There will be two arms of parenteral (iv) iron supplementation (ferric carboxymaltose and ferric gluconate) and one arm of oral supplementation (sucrosomial iron). Primary objective of the study is is to compare the efficacy of oral iron with that of the iv iron supplementation regimens. The primary outcome is measured as the percentage of patients responsive to iron supplementation. Response is defined by Hb normalization or by an Hb increase ≥2 g/dL by week 8 from start of therapy. As secondary objectives the influence of anemia and its treatment on fatigue, quality of life, hospitalizations, additional outpatient visits, number of endoscopic examinations; further treatments and relative side effects will be evaluated.

Conditions

Iron Deficiency Anemia; Inflammatory Bowel Diseases

Keywords

anemia; iron deficiency; Crohn's disease; Ulcerative colitis

Outcome Measures

Primary Outcomes (1)

• Relative efficacy of the three iron supplementation regimens

  Primary endpoint of the trial is to compare the efficacy of oral iron with that of the iv iron supplementation regimens in the treatment of IDA in IBD. The primary comparison of interest regards the 2 combined iv regimens vs. the oral iron supplementation. Non inferiority of the oral regimen is hypothesized. Primary outcome measure is the proportion of patients responsive to iron supplementation. Response is defined by Hb normalization or by an Hb increase ≥2 g/dL by week 8. Normalization of Hb occurs with Hb values ≥12 g/dL in females or ≥13 g/dL in males.

  The primary outcome will be measured at week 8 from start of iron supplementation

Secondary Outcomes (4)

• Safety evaluation: Adverse events

  Enrollment to 24 weeks

• Influence of anemia and its treatment on fatigue

  Enrollment to 24 weeks

• Evaluation of quality of life

  Enrollmen to to 24 weeks

• Number of hospitalizations, additional outpatient visits, number of endoscopic examinations, further treatments

  Enrollment to 24 weeks

Other Outcomes (4)

• Serum Hepcidin

  8 weeks

• Serul IL-6

  Enrollment

• Serum IL-1 beta

  Enrollment

Study Arms (3)

Sucrosomial iron

EXPERIMENTAL

One or two capsules/die of sucrosomial iron will be assumed by the participant, depending on hemoglobin (Hb) concentration and participant body weight, for 8 weeks. Each capsule contains 30 mg of iron.

Drug: Sucrosomial iron

Ferric gluconate

ACTIVE COMPARATOR

Ferric gluconate will be administered by iv infusion, 125 mg of elemental iron once or twice weekly for 4 or 8 weeks depending on Hb concentration and patient body weight.

Drug: Ferric Gluconate

Ferric carboxymaltose

ACTIVE COMPARATOR

Two or three iv infusions of 500-1000 mg of elemental iron will be given as ferric carboxymaltose, over a 4 week period. Dosage and number of infusions will be established depending on Hb concentration and patient body weight.

Drug: Ferric carboxymaltose

Interventions

Sucrosomial iron DRUG

This is an oral iron formulation commercially available as an integrator

Also known as: Sideral

Sucrosomial iron

Ferric Gluconate DRUG

This is a commercially available iron formulation for parenteral administration

Also known as: Ferrlecit

Ferric gluconate

Ferric carboxymaltose DRUG

This is a commercially available iron formulation for parenteral administration

Also known as: Ferinject

Ferric carboxymaltose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be included in the trial the patient must:
• Have given written informed consent to participate
• Be aged 18 years and over
• Have a BMI \>16
• Have IBD and IDA with or without inflammation

You may not qualify if:

• Patients with hypersensitivity to the IMPs, to other iron containing products and to sucrose or benzil alcohol will be excluded from the study.
• Pregnancy, lactation and women of childbearing potential (WOCBP) (i.e. fertile, following menarche and until becoming post-menopausal, no menses for 12 months without an alternative medical cause, unless permanently sterile) that are not willing to use highly efficient contraceptive measures according to the CTFG recommendations on contraception (Table 4);
• male patients with WOCBP partners who are unwilling to use highly efficient contraceptive measures (Table 4);
• an history of erythropoietin treatment within 4 weeks prior to recruitment;
• alcohol abuse, liver cirrhosis, active hepatitis or signs of liver disease with a Child-Pugh class B or C;
• chronic renal failure stage 3 or higher (estimated glomerular filtration rate \<60mL/min as determined using either the CKD-EPI equation, the MDRD equation or the Cockcroft-Gault formula);
• major surgery in the previous 3 months;
• significant overt bleeding, acute severe anemia with hemodynamic instability;
• active malignancy and any hematologic disease causing anemia;
• known active infection;
• known human immunodeficiency virus HCV and HBV infections;
• evidence of tubercular (TB) infection (see section 5.2.1 for the TB screening criteria necessary to rule out active or latent TB infection).

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead
• Italian Group for the study of Inflammatory Bowel Disease (IG-IBD): collaborator

Study Sites (1)

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

RECRUITING

Related Publications (4)

• Nutritional anaemias. Report of a WHO scientific group. World Health Organ Tech Rep Ser. 1968;405:5-37. No abstract available.

  PMID: 4975372 BACKGROUND

• Dignass AU, Gasche C, Bettenworth D, Birgegard G, Danese S, Gisbert JP, Gomollon F, Iqbal T, Katsanos K, Koutroubakis I, Magro F, Savoye G, Stein J, Vavricka S; European Crohn's and Colitis Organisation [ECCO]. European consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases. J Crohns Colitis. 2015 Mar;9(3):211-22. doi: 10.1093/ecco-jcc/jju009. Epub 2014 Dec 3. No abstract available.

  PMID: 25518052 BACKGROUND

• Ciccocioppo R, Klersy C, Russo ML, Valli M, Boccaccio V, Imbesi V, Ardizzone S, Porro GB, Corazza GR. Validation of the Italian translation of the Inflammatory Bowel Disease Questionnaire. Dig Liver Dis. 2011 Jul;43(7):535-41. doi: 10.1016/j.dld.2010.12.014. Epub 2011 Feb 18.

  PMID: 21315666 BACKGROUND

• Bergamaschi G, Di Sabatino A, Albertini R, Ardizzone S, Biancheri P, Bonetti E, Cassinotti A, Cazzola P, Markopoulos K, Massari A, Rosti V, Porro GB, Corazza GR. Prevalence and pathogenesis of anemia in inflammatory bowel disease. Influence of anti-tumor necrosis factor-alpha treatment. Haematologica. 2010 Feb;95(2):199-205. doi: 10.3324/haematol.2009.009985. Epub 2009 Oct 8.

  PMID: 19815838 BACKGROUND

Related Links

• RIDART studies site
• RIDART I study site

MeSH Terms

Conditions

Anemia, Iron-Deficiency; Inflammatory Bowel Diseases; Anemia; Iron Deficiencies; Crohn Disease; Colitis, Ulcerative

Interventions

sucrosomial iron; ferric gluconate; ferric carboxymaltose

Condition Hierarchy (Ancestors)

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

Study Officials

• Antonio Di Sabatino, MD

  Fondazione IRCCS Policlinico San Matteo di Pavia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Antonio Di Sabatino, MD

CONTACT

+39 3357425904; adisabatino@smatteo.pv.it

Gaetano Bergamaschi, MD

CONTACT

+39 3403811265; gaetanobergamaschi@libero.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Three iron supplementation regimens will be compared in terms of effectiveness and safety in the treatment of IBD-associated IDA. Primary outcome is the relative effectiveness of an oral iron supplementation regimen compared with two iv iron regimens.

Study Record Dates

• First Submitted: October 7, 2020
• First Posted: October 14, 2020
• Study Start: January 1, 2020
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: October 19, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)