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

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ClinicalTrials.gov Identifier: NCT03524651
Recruitment Status : Recruiting
First Posted : May 15, 2018
Last Update Posted : July 3, 2018
Sponsor:
Collaborators:
Attikon Hospital
General Hospital of Chalkida
Information provided by (Responsible Party):
Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.

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.

Condition or disease Intervention/treatment Phase
Iron Deficiency Anemia Drug: Ferrous Sulfate Drug: Fe-ASP Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-dummy, blind, randomized, phase IV clinical trial
Masking: Double (Participant, Investigator)
Masking Description: Double blind
Primary Purpose: Treatment
Official Title: Ferrous Acetyl-Aspartate Casein Formulation Evaluation Over Ferrous Sulfate in Iron Deficiency Anemia (ACCESS): A Double-Dummy Randomized Clinical Trial
Actual Study Start Date : May 2, 2018
Estimated Primary Completion Date : December 1, 2018
Estimated Study Completion Date : March 1, 2019


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 Name: Microfer

Drug: Ferrous Sulfate
Boxes of 10 vials of 15 ml containing inactive ingredients of Omalin.
Other Name: 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 Name: Omalin

Drug: Fe-ASP
Blisters of 10 capsules containing inactive ingredients of Microfer.
Other Name: Microfer placebo




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. Ferritin levels [ Time Frame: 4 weeks and 12 weeks ]
    Differences between the two groups of treatment in ferritin levels.

  3. Absolute reticulocyte count [ Time Frame: 1 week, 4 weeks and 12 weeks ]
    Differences between the two groups of treatment in absolute reticulocyte count.

  4. 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.

  5. 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.

  6. 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.

  7. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03524651


Contacts
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Contact: Evangelos Giamarellos-Bourboulis, MD, PhD 0030 210 5831994 egiamarel@med.uoa.gr

Locations
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Greece
General Hospital of Chalkida Not yet recruiting
Chalkida, Greece, 34100
Contact: Nikolaos Tsokos, MD    30 22213 50459    ntsokos@hotmail.com   
Principal Investigator: Nikolaos Tsokos, MD         
Sub-Investigator: Georgios Haliotis, MD         
Attikon University Hospital Recruiting
Haidari/Athens, Greece, 12462
Contact: Evangelos Giamarellos-Bourboulis, MD, PhD    0030 210 5831994    egiamarel@med.uoa.gr   
Principal Investigator: Evangelos Giamarellos-Bourboulis, MD, PhD         
Sub-Investigator: Maria Argiropoulou, MD         
Sub-Investigator: Evdoxia Kiriazopoulou, MD         
Sponsors and Collaborators
Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.
Attikon Hospital
General Hospital of Chalkida
Investigators
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Principal Investigator: Evangelos Giamarellos-Bourboulis, MD, PhD Attikon University Hospital
Principal Investigator: Nikolaos Tsokos, MD General Hospital of Halkida

Publications:
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Responsible Party: Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.
ClinicalTrials.gov Identifier: NCT03524651     History of Changes
Other Study ID Numbers: Omalin-01/ACCESS
First Posted: May 15, 2018    Key Record Dates
Last Update Posted: July 3, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.:
Iron Deficiency Anemia
Fe-ASP
Casein
Iron protein acetyl aspartate
Restoration of decreased hemoglobin
Ferrous sulfate
Additional relevant MeSH terms:
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Anemia
Anemia, Iron-Deficiency
Deficiency Diseases
Hematologic Diseases
Anemia, Hypochromic
Iron Metabolism Disorders
Metabolic Diseases
Malnutrition
Nutrition Disorders
Iron
Caseins
N-Methylaspartate
Trace Elements
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Excitatory Amino Acid Agonists
Excitatory Amino Acid Agents
Neurotransmitter Agents