Ferrous Acetyl-Aspartate Casein Formulation Evaluation Over Ferrous Sulfate in Iron Deficiency Anemia

NCT ID: NCT03524651

Last Updated: 2021-04-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-02
• Study Completion Date: 2021-01-08

Brief Summary

The scope of this study is to compare the efficacy of the new oral formulation of Fe-ASP to oral ferrous sulfate in patients with iron deficiency anemia (IDA) for the restoration of decreased circulating Hb. The improvement of symptoms of anemia, the restoration of biomarkers of iron deficiency into the normal range and the incidence of GI tract side effects are the study secondary endpoints.

Detailed Description

Anemia is a major problem in the general population affecting 5.6% in the United States. Iron deficiency is the most common cause of anemia. Although traditionally considered to be mainly a problem of underdeveloped countries, a recent epidemiological survey reported high incidence of iron deficiency anemia (IDA) in Europe in 2011. The incidence rate measured per 1,000 person-years was 8.18 in Belgium, 8.93 in Italy, 12.42 in Germany and 14.14 in Spain. Women were affected four-times more than men. The major causes of IDA are chronic blood loss, chronic disorders and excess needs.

The cornerstones of management of IDA are recognition and management of the cause of iron loss and efficient iron supplementation. Iron supplementation is usually done through oral formulations of iron. Three oral iron preparations are broadly used: ferrous sulfate, ferrous gluconate, and ferrous fumarate. The usual dosage is 325 mg (corresponding to 65 mg of elemental iron) two times a day. One major limitation with oral iron supplementation is GI side effects observed in almost 40% of cases. These are gastric discomfort, nausea, vomiting and constipation and they are caused due to the oxidation of ferrous irons in the stomach by acidic gastric fluid into insoluble salts.

A new formulation of iron conjugated to one N-acetyl-aspartate derivative of casein (Fe-ASP) has recently been developed. Due to the casein coating, it is anticipated that iron is converted to a smaller extent in the stomach into insoluble salts. In this way, more iron reaches the duodenum to become absorbed whereas GI side effects are less often. In parallel, animal studies have shown that casein itself primes the expression of enzymes that facilitate the absorption of iron across the duodenal mucosa.

This formulation is anticipated to be better tolerated for oral ingestion since iron is readily absorbed in the duodenum. The aim is to compare the efficacy of the new oral formulation of Fe-ASP to oral ferrous sulfate in patients with IDA for the restoration of decreased circulating Hb.

Conditions

Iron Deficiency Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Ferrous sulfate

Patients will take every day for 12 weeks two oral capsules of 150 mg ferrous sulfate delivering 47 mg of active elemental iron. Capsules should be taken orally either two hours before meal or two hours after meal. The same patients will take every day on exactly the same time for 12 weeks two placebo vials of 15 ml volume with excipients contained in the commercially available formulation Fe-Asp Omalin (Uni-Pharma SA).

Group Type: ACTIVE_COMPARATOR

Ferrous Sulfate

Intervention Type: DRUG

Blisters of 10 capsules containing 150 mg of ferrous sulfate.

Ferrous Sulfate

Intervention Type: DRUG

Boxes of 10 vials of 15 ml containing inactive ingredients of Omalin.

Fe-ASP

Patients will take every day for 12 weeks two oral placebo capsules. Capsules should be taken orally either two hours before meal or two hours after meal. The same patients will take every day on exactly the same time for 12 weeks two vials of 15 ml volume of the Fe-Asp preparation Omalin (Uni-Pharma SA) delivering 40 mg of elemental iron.

Group Type: ACTIVE_COMPARATOR

Fe-ASP

Intervention Type: DRUG

Boxes of 10 vials of 15 ml containing 800 mg of Iron protein acetyl aspartate.

Fe-ASP

Intervention Type: DRUG

Blisters of 10 capsules containing inactive ingredients of Microfer.

Interventions

Ferrous Sulfate

Blisters of 10 capsules containing 150 mg of ferrous sulfate.

Intervention Type: DRUG

Fe-ASP

Boxes of 10 vials of 15 ml containing 800 mg of Iron protein acetyl aspartate.

Intervention Type: DRUG

Ferrous Sulfate

Boxes of 10 vials of 15 ml containing inactive ingredients of Omalin.

Intervention Type: DRUG

Fe-ASP

Blisters of 10 capsules containing inactive ingredients of Microfer.

Intervention Type: DRUG

Other Intervention Names

Microfer; Omalin; Omalin placebo; Microfer placebo

Eligibility Criteria

Inclusion Criteria

• Male or female
• Age equal to or more than 18 years
• Written informed consent provided by the patient
• Hb below 10g/dl, as defined by other trials
• Absolute red blood cell (RBC) count below 4.5 x 106/mm3 for men or 4.0 x 106/mm3 for women
• Mean corpuscular volume (MCV) of RBCs below 80 fl
• Mean corpuscular Hb (MCH) of RBCs below 27 pg
• Total ferritin below 30 ng/ml; this criterion is associated with sensitivity more than 99% for iron deficiency

Exclusion Criteria

• Age below 18 years
• Denial to provide written informed consent
• Acute myelogenous or lymphoblastic leukemia
• Multiple myeloma
• Primary or secondary myelodysplastic syndrome
• Planning for start of chemotherapy within the first 30 days after inclusion in the trial
• Planning for start of radiotherapy within the first 30 days after inclusion in the trial
• Intake of erythropoietin
• Planning for start of erythropoietin within the first 30 days after inclusion in the trial
• Intake of chemotherapy the last six months
• Intake of radiotherapy the last six months
• Known hemochromatosis
• Known celiac disease
• Liver cirrhosis of Child-Pugh stage II or III
• Any active overt bleeding
• Pregnancy or lactation

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Attikon Hospital

OTHER

Sponsor Role: collaborator

Amalia Fleming Prefecture General Hospital of Melissia

UNKNOWN

Sponsor Role: collaborator

G.Gennimatas General Hospital

OTHER

Sponsor Role: collaborator

Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Evangelos Giamarellos-Bourboulis, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Attikon Hospital

Nikolaos Tsokos, MD

Role: PRINCIPAL_INVESTIGATOR

Amalia Fleming Prefecture General Hospital of Melissia

Georgios Adamis, MD

Role: PRINCIPAL_INVESTIGATOR

G.Gennimatas General Hospital

Locations

General Hospital of Athens G. Gennimatas

Athens, , Greece

Attikon University Hospital

Haidari/Athens, , Greece

Amalia Fleming Prefecture General Hospital of Melissia

Melíssia, , Greece

Countries

Greece

References

Lazzari F, Carrara M. Overview of clinical trials in the treatment of iron deficiency with iron-acetyl-aspartylated casein. Clin Drug Investig. 2005;25(11):679-89. doi: 10.2165/00044011-200525110-00001.

Reference Type: BACKGROUND

PMID: 17532714 (View on PubMed)

Other Identifiers

Omalin-01/ACCESS

Identifier Type: -

Identifier Source: org_study_id