A Randomised, Double-blinded, Parallel Group Study to Demonstrate the Adherence and Efficacy of Different Doses of Iron Supplement in Subjects With or At-risk of Iron Deficiency With a History of Intolerance to Oral Iron
试验速览
- 阶段
- 不适用
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Proportion of subjects adherent/persistant (12 weeks)
研究概览
简要总结
A randomized, placebo controlled, parallel group, double blind study to compare the 3-month adherence and efficacy of Active Iron in subjects with or at-risk of iron deficiency and a history of intolerance to oral iron. Subjects with intolerance and treatment failure due to oral iron (male and female subjects, aged 18 to 55 years, with mild to moderate iron deficiency, with or without anaemia) are eligible. Sixty subjects are randomised into three groups (14 mg elemental iron, 25mg elemental iron and 50mg elemental iron daily). The primary objective is to assess adherence/persistence (including using pill counts). Secondary objectives are to assess gastrointestinal tolerability, haematological efficacy and health related quality of life.
详细描述
More than 2.2. billion people worldwide have anaemia and half of this burden is caused by iron deficiency [Lopez 2016]. The commonest causes of iron deficiency are inadequate intake, poor absorption of iron [Stoffel 2017] and blood loss, for example due to menstruation [World Health Organization Guideline: Daily iron supplementation in adult women and adolescent girls; Geneva 2016, Low 2016]. Supplementation with oral iron is well established to prevent and treat iron deficiency anaemia and to promote recovery of iron and haemoglobin levels post blood loss or blood donation [Low 2016, McNamee 2013]. However, iron food fortification and oral iron supplements are frequently limited by poor absorption and poor tolerability [Munoz 2009]. Ferrous sulfate is considered the gold standard and the only oral iron form on the WHO Essential Medicines List, yet has fractional absorption of only 16%-21% from daily or alternative daily doses [Stoffel et al 2017]. It is also poorly tolerated, causing adverse GI effects in a majority of patients [Pereira 2014]. This results in poor adherence in up to 50% of users, significant nutritional deficit and treatment failure [Tolkien 2015]
We have previously evaluated a formulation of microspheres of iron sulfate in a denatured whey protein (WP) matrix at a daily elemental iron dose of 25mg daily, marketed as Active Iron, in comparison with equi-dose immediate release and modified release ferrous sulfate (Wang et al. Acta Haematologica Acta Haematol 2017;138:223-232). In these evaluations, the iron-WP formulation has shown better absorption and there were no reports of adverse effects. Furthermore, in-vitro data show that the iron-WP matrix formulation can protect HT20 gut endothelial cells and CaCO2 cells from oxidative stress and cell damage associated with ferrous sulfate. In a post-marketing survey of 101 people taking Active Iron (age 43 ± 10 years, 83% female) with a history of intolerance to oral iron, 87% reported no adverse effects after 2 weeks.
Therefore, the present study aims to compare the 3-month adherence and efficacy associated with a 25mg single daily dose, a lower (14mg) single daily dose and twice daily dosing with 25mg (50mg daily), in subjects with treatment failure (iron deficiency and with a history of intolerance to oral iron). The primary objective of the study is to assess the proportion of subjects adherent and persistent (>80% based on pill counts) from baseline to weeks 6 and baseline to week 12. Secondary objectives aim to further assess compliance (average compliance), tolerability (incidence of gastrointestinal symptoms GSRS instrument), efficacy (change in haemoglobin, ferritin, transferrin saturation, iron binding protein) and health related quality of life (SF36 instrument).
At least 90 subjects will be screened in order to identify up to 60 eligible subjects, and 54 evaluable subjects. Participants will be male and female, between 18 and 55 years of age, with mild to moderate iron deficiency anaemia (haemoglobin ≥9.5 g/dL and <12.0 g/dL for females and ≥10.0 g/dL and <13.0 g/dL for males and ferritin < 30 µg/L) or ferritin < 30 µg/L and no anaemia. There will be stratified randomisation to include up to 30 patients with iron deficiency and mild to moderate anaemia as well as up to 30 patients with iron deficiency without anaemia. Other pre-specified sub-groups for evaluation of the primary and secondary endpoints include women with reported symptoms of heavy menstrual bleeding and participants with intolerance of liquid iron products or lower doses (< 50mg elemental iron). Separate analysis of primary and secondary endpoints will be carried out in participants in the multivitamin and mineral sub study. Finally, due to the suspension of some clinics during Covid lockdown, we carried out a prespecified analysis of patients completing the study before the onset of the Covid 19 Pandemic.
Subjects will be randomised to one of three treatment arms:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Subjects will be randomized into one of three arms (20 subjects per arm) but will be blinded as to which group they are in. The three arms are as follows:
Group 1: ACTIVE IRON™ (ferrous sulfate) 14 mg elemental iron once daily (and matching placebo) Group 2: ACTIVE IRON™ (ferrous sulfate) 25 mg elemental iron once daily (and matching placebo) Group 3: ACTIVE IRON™ (ferrous sulfate) 25 mg elemental iron twice daily (and matching placebo)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Be able to give written informed consent
- •Be between 18 and 55 years of age
- •Have ferritin levels <30 µg/L
- •Have a history of intolerance to oral iron
- •Have mild to moderate anaemia (haemoglobin ≥9.5 g/dL and <12.0 g/dL for females and ≥10.0 g/dL and <13.0 g/dL for males, up to 30 patients) or no anaemia (up to 30 patients)
- •Be in generally good health as determined by the investigator
排除标准
- •A history of dairy allergy or are hypersensitive to any of the components of the test product,
- •Are currently taking any iron supplements, or have done so in the previous 2 weeks,
- •Current inflammatory bowel disease (Crohn's disease or ulcerative colitis),
- •Severe anemia (females with hemoglobin <9.5 g/dL and males with hemoglobin <10.0 g/dL)
- •Females that have started menopause,
- •Females using extended-cycle birth control pills
- •Have a significant acute or chronic, unstable and untreated disease or any condition, which contraindicates, in the investigator's judgement, entry to the study,
- •Having a condition or have taken a medication that the investigator believes would interfere with the objectives of the study, pose a safety risk or confound the interpretation of the study results; for example, no concurrent medication which interferes with the absorption of iron (e.g. tetracyclines, calcium supplements),
- •Individuals who, in the opinion of the investigator, are considered to be poor attendees or unlikely for any reason to be able to comply with the trial,
- •Subjects may not be receiving treatment involving experimental drugs. If the subject has been in a recent experimental trial, these must have been completed not less than 30 days prior to this study,
- •Have a malignant disease or any concomitant end-stage organ disease.
结局指标
主要结局
Proportion of subjects adherent/persistant (12 weeks)
时间窗: 12 weeks
To assess the change in proportion of subjects adherent/persistant (\>80% based on pill counts) from baseline to week 12
Proportion of subjects adherent/persistent (6 weeks)
时间窗: 6 weeks
To assess the change in proportion of subjects adherent/persistent (\>80% based on pill counts) from baseline to week 6
次要结局
- Upper gastrointestinal symptoms (12 weeks)(12 weeks)
- Change in haemaglobin (12 weeks)(12 weeks)
- Change in ferritin (12 weeks)(12 weeks)
- Lower gastrointestinal symptoms (12 weeks)(12 weeks)
- Change in GSRS (12 weeks)(12 weeks)
- Change in health related quality of life (12 weeks)(12 weeks)
- Change in transferrin saturation (12 weeks)(12 weeks)