A Study to Demonstrate the Efficacy and Tolerability of Ferrous Bisglycinate Chelate in Iron Deficiency Anaemia and to Compare These With Those of Ferrous Ascorbate.
Condition: Haematopoiesis
MeSH terms: Anemia, Iron-Deficiency; Iron Deficiencies
Study type: Interventional
Phase: Phase 3

Summary: 
      Iron deficiency anaemia (Haemoglobin, Hb < 12gm/dl) is one of India's major public health
      problems particularly in women. Effective control of iron deficiency anaemia decreases the
      incidence of fatigue, bodyache, headache, lack of concentration and menstrual complications.
      Iron bisglycine chelate has been used successfully to treat iron deficiency anaemia and is
      also a well tolerated therapy. Use of ferrous bisglycinate chelate one tablet daily as a
      nutritional supplement is well established in India. For treatment of iron deficiency
      anaemia, some women may need 1 tablet/day, while some may need 2 tablets/day. In India,
      ferrous ascorbate, 1 tablet daily is a widely accepted form of treatment for iron deficiency
      anaemia. The primary purpose of this study is to demonstrate the efficacy and tolerability
      profile of ferrous bisglycinate chelate to support the registration of this product as a
      'drug' in India. Comparative data between ferrous bisglycinate chelate and ferrous ascorbate
      will also augment our existing knowledge, which will further support appropriate use of
      ferrous bisglycinate chelate for the treatment of iron deficiency anaemia. Study design and
      patient population: This will be a multicentre, randomized, laboratory-blinded, parallel-
      group study. It is projected that the study will randomize 270 women (90 subjects in each
      treatment arm) with iron deficiency anaemia (Hb 6-9 gm/dl + serum Ferritin <15 μg/l) to
      either ferrous bisglycinate chelate 1 or 2 tablets/day, or ferrous ascorbate 1 tablet/day for
      8 weeks. At fortnightly visits, blood will be collected for Hb (to evaluate efficacy),
      adverse events will be documented (to evaluate tolerability), the investigational drugs will
      be dispensed and reasons for non compliance will be recorded. Study endpoints: The primary
      endpoint is defined as the rise of Hb from baseline after 8 weeks of treatment in each
      ferrous bisglycinate chelate group (1 tablet/day and 2 tablets/day). The secondary endpoints
      include the difference in the average change in Hb, difference in the rate of rise of Hb,
      difference in the proportion of patients who achieve a target Hb ≥12gm/dl and difference in
      the % incidence of gastrointestinal side effects during 8 week therapy with 2 dosing regimens
      of ferrous bisglycinate chelate (1 tablet/day and 2 tablets/day) and ferrous ascorbate 1
      tablet/day.
    

Detailed description: 
      Rationale Iron deficiency is the most common form of malnutrition globally. In India, nearly
      70% of women are estimated to be iron deficient. Iron deficiency anemia (IDA, Hb <12gm/dl) is
      a very late manifestation of iron deficiency. IDA is a consequence of decreased iron intake,
      increased iron loss from the body or increased iron requirements Blood loss during
      menstruation can predispose women to have poor iron stores and the presence of excess
      menstrual bleeding can contribute to the development of IDA in women. Patients with IDA
      usually present with fatigue, headache, bodyache, paraesthesia and lack of concentration. IDA
      can cause menorrhagia, which in turn can aggravate IDA. With severe anemia, there may be
      amenorrhoea as well.

      Iron deficiency anaemia is often treated with iron tablets such as ferrous sulphate, ferrous
      fumarate and ferrous gluconate. It usually takes about 6-10 weeks for Hb to return to normal
      after initiation of oral iron therapy. Although efficacious from a haematological point of
      view, most of these therapies are associated with limiting gastrointestinal side effects
      (e.g. nausea, vomiting, constipation, diarrhoea and abdominal pain), which eventually reduce
      patient compliance.

      Among the recent alternatives, iron bisglycine chelate has been used successfully to treat
      iron deficiency anaemia and is also a well tolerated therapy.

      Use of ferrous bisglycinate chelate (each tablet contains 60mg of elemental iron as ferrous
      bisglycinate chelate, 1 mg folic acid, 5 mcg cyanocobalamin and 15 mg zinc bis-glycinate), 1
      tablet daily is well established as a nutritional supplement in India. However, for treatment
      of iron deficiency anaemia, some women may need 1 tablet/day, while some may need 2 tablets
      /day.

      In India, ferrous ascorbate tablets (each tablet contains 100 mg elemental iron as ferrous
      ascorbate, with 1 mg folic acid) in the recommended dose of 1 tablet daily are a widely
      accepted form of treatment for iron deficiency anaemia.

      The primary purpose of this study is to demonstrate the efficacy and tolerability profile of
      ferrous bisglycinate chelate to support the registration of this product as a 'drug' in
      India. Comparative data between ferrous bisglycinate chelate and ferrous ascorbate will also
      augment our existing knowledge, which will further support the use of ferrous bisglycinate
      chelate for the treatment of iron deficiency anaemia.

      Objective(s)

      Primary:

      To estimate the mean rise in haemoglobin level in patients with iron deficiency anaemia after
      8 weeks of treatment (vs. baseline) with ferrous bisglycinate chelate (1 tablet and 2 tablets
      daily).

      Secondary:

        1. To compare the mean rise in haemoglobin in patients with iron deficiency anaemia after 8
           weeks treatment with ferrous bisglycinate chelate, 1 tablet and 2 tablets daily vs.
           ferrous ascorbate 1 tablet daily.

        2. To compare the average rate of rise of haemoglobin during 8 weeks of treatment with
           ferrous bisglycinate chelate 1 tablet daily, ferrous bisglycinate chelate 2 tablets
           daily and ferrous ascorbate 1 tablet daily.

        3. To compare the proportion of patients who achieve a target Hb ≥ 12gm/dl after 8 weeks of
           treatment with ferrous bisglycinate chelate 1 tablet daily, ferrous bisglycinate chelate
           2 tablets daily and ferrous ascorbate 1 tablet daily.

        4. To compare the % incidence of gastrointestinal side effects during 8 weeks treatment
           with ferrous bisglycinate chelate 1 tablet daily, ferrous bisglycinate chelate 2 tablets
           daily and ferrous ascorbate 1 tablet daily.

      Study Design This will be a multicentre, randomized, laboratory-blinded, parallel-group
      study. It is projected that the study will randomize 270 women (90 subjects in each treatment
      arm) with iron deficiency anaemia (Hb 6-9 gm/dl + serum Ferritin <15 μg/l) to either ferrous
      bisglycinate chelate 1 tablet/day, ferrous bisglycinate chelate 2 tablets/day or ferrous
      ascorbate 1 tablet/day for 8 weeks. At fortnightly visits, blood will be collected for Hb (to
      evaluate efficacy), adverse events will be documented (to evaluate tolerability), the
      investigational drugs will be dispensed and reasons for non compliance will be recorded.

      The total study duration consists of an 8-week treatment period and will involve 6 clinic
      visits.

      Study Endpoints/Assessments Primary Endpoint(s) Rise of haemoglobin from baseline to 8 weeks
      in each ferrous bisglycinate chelate group (1 tablet daily and 2 tablets daily).

      Secondary Endpoint(s)

        1. The difference in the average change in Hb from baseline to 8 weeks with ferrous
           bisglycinate chelate 1 and 2 tablets daily, and ferrous ascorbate 1 tablet daily.

        2. The difference in the average rate of rise of Hb during 8 weeks of treatment with
           ferrous bisglycinate chelate 1 tablet daily, ferrous bisglycinate chelate 2 tablets
           daily, and ferrous ascorbate 1 tablet daily.

        3. The difference in proportion of patients who achieve a target Hb ≥12gm/dl after 8 weeks
           of treatment with ferrous bisglycinate chelate 1 tablet daily, ferrous bisglycinate
           chelate 2 tablets daily, and ferrous ascorbate 1 tablet daily.

        4. The difference in % incidence of gastrointestinal side effects during 8 weeks treatment
           with ferrous bisglycinate chelate 1 tablet daily, ferrous bisglycinate chelate 2 tablets
           daily and ferrous ascorbate 1 tablet daily.
    

Intervention name(s): ferrous ascorbate; ferrous bisglycinate chelate 1 OD; ferrous bisglycinate chelate 2 OD
Intervention type(s): Drug; Dietary Supplement; Dietary Supplement
Intervention description(s): 100 mg elemental iron; 60 mg elemental iron; 120 mg elemental iron
Intervention MeSH terms: Ascorbic Acid; Chelating Agents; Glycine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Other