Clinical trial NCT03524651: Ferrous Acetyl-Aspartate Casein Formulation Evaluation Over Ferrous Sulfate in Iron Deficiency Anemia
Official title: Ferrous Acetyl-Aspartate Casein Formulation Evaluation Over Ferrous Sulfate in Iron Deficiency Anemia (ACCESS): A Double-Dummy Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Iron Deficiency Anemia
Keywords: Iron Deficiency Anemia
Fe-ASP
Casein
Iron protein acetyl aspartate
Restoration of decreased hemoglobin
Ferrous sulfate
Lead sponsor: Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.
Sponsor class: INDUSTRY
Collaborators: name: Attikon Hospital
name: Amalia Fleming Prefecture General Hospital of Melissia
name: G.Gennimatas General Hospital
First posted: 2018-05-15
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-dummy, blind, randomized, phase IV clinical trial
Primary purpose: TREATMENT

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.

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
* 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

Primary outcomes:
measure: Comparative increase of baseline Hb
timeFrame: 4 weeks
Secondary outcomes:
measure: Normalization of Hb
timeFrame: 4 weeks and 12 weeks
measure: Ferritin levels
timeFrame: 4 weeks and 12 weeks
measure: Absolute reticulocyte count
timeFrame: 1 week, 4 weeks and 12 weeks
measure: Absolute RBC count, Hb, MCV and MCH
timeFrame: 4 weeks and 12 weeks
measure: Fatigue symptoms of IDA
timeFrame: 4 weeks and 12 weeks
measure: Physical findings of IDA
timeFrame: 4 weeks and 12 weeks
measure: Incidence of GI side effects
timeFrame: 4 weeks and 12 weeks
Other outcomes:
Locations:
city: Athens
country: Greece
facility: General Hospital of Athens G. Gennimatas
city: Haidari/Athens
country: Greece
facility: Attikon University Hospital
city: Melíssia
country: Greece
facility: Amalia Fleming Prefecture General Hospital of Melissia
Study officials:
affiliation: Attikon Hospital
name: Evangelos Giamarellos-Bourboulis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Amalia Fleming Prefecture General Hospital of Melissia
name: Nikolaos Tsokos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: G.Gennimatas General Hospital
name: Georgios Adamis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.