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

April 8, 2021 updated by: Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.

Ferrous Acetyl-Aspartate Casein Formulation Evaluation Over Ferrous Sulfate in Iron Deficiency Anemia (ACCESS): A Double-Dummy Randomized Clinical Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Greece
      • Athens, Greece, 115 27
        • General Hospital of Athens G. Gennimatas
      • Haidari/Athens, Greece, 12462
        • Attikon University Hospital
      • Melíssia, Greece, 15127
        • Amalia Fleming Prefecture General Hospital of Melissia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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
  • In the case of patients with anemia after GI tract hemorrhage, inclusion criteria 6 and 7 DO NOT apply for study inclusion.

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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).
Drug: Ferrous Sulfate
Blisters of 10 capsules containing 150 mg of ferrous sulfate.
Other Names:
  • Microfer
Drug: Ferrous Sulfate
Boxes of 10 vials of 15 ml containing inactive ingredients of Omalin.
Other Names:
  • Omalin placebo
Active Comparator: 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.
Drug: Fe-ASP
Boxes of 10 vials of 15 ml containing 800 mg of Iron protein acetyl aspartate.
Other Names:
  • Omalin
Drug: Fe-ASP
Blisters of 10 capsules containing inactive ingredients of Microfer.
Other Names:
  • Microfer placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparative increase of baseline Hb
Time Frame: 4 weeks
The primary study endpoint is the comparative increase of baseline Hb in each study group after the first 4 weeks of treatment. Since the daily amount of elemental iron delivered with the ferrous sulfate regimen is 94 mg and with the Fe-ASP regimen 80 mg, the increase of baseline Hb will be adjusted per mg of delivered elemental iron.
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Normalization of Hb
Time Frame: 4 weeks and 12 weeks
Differences between the two groups of treatment in normalization of Hb; this is defined as Hb≥13 g/dl for mean and ≥12 g/dl for women.
4 weeks and 12 weeks
Ferritin levels
Time Frame: 4 weeks and 12 weeks
Differences between the two groups of treatment in ferritin levels.
4 weeks and 12 weeks
Absolute reticulocyte count
Time Frame: 1 week, 4 weeks and 12 weeks
Differences between the two groups of treatment in absolute reticulocyte count.
1 week, 4 weeks and 12 weeks
Absolute RBC count, Hb, MCV and MCH
Time Frame: 4 weeks and 12 weeks
Differences between the two groups of treatment in absolute RBC count, Hb, MCV and MCH.
4 weeks and 12 weeks
Fatigue symptoms of IDA
Time Frame: 4 weeks and 12 weeks
Differences between the two groups of treatment in change of the fatigue symptoms of IDA.
4 weeks and 12 weeks
Physical findings of IDA
Time Frame: 4 weeks and 12 weeks
Differences between the two groups of treatment in change of physical findings of IDA.
4 weeks and 12 weeks
Incidence of GI side effects
Time Frame: 4 weeks and 12 weeks
Differences between the two groups of treatment in the incidence of GI side effects.
4 weeks and 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.

Collaborators

Attikon Hospital
Amalia Fleming Prefecture General Hospital of Melissia
General Hospital of Athens G. Gennimatas

Investigators

  • Principal Investigator: Evangelos Giamarellos-Bourboulis, MD, PhD, Attikon Hospital
  • Principal Investigator: Nikolaos Tsokos, MD, Amalia Fleming Prefecture General Hospital of Melissia
  • Principal Investigator: Georgios Adamis, MD, General Hospital of Athens G. Gennimatas

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 2, 2018

Primary Completion (Actual)

January 8, 2021

Study Completion (Actual)

January 8, 2021

Study Registration Dates

First Submitted

May 2, 2018

First Submitted That Met QC Criteria

May 2, 2018

First Posted (Actual)

May 15, 2018

Study Record Updates

Last Update Posted (Actual)

April 9, 2021

Last Update Submitted That Met QC Criteria

April 8, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Omalin-01/ACCESS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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