An Epidemiological Study to Assess the Prevalence of Iron Overload Using MRI in Patients With Transfusional Siderosis (TIMES Study)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 243
- 试验地点
- 14
- 主要终点
- Percentage of Participants With Cardiac and Liver Iron Overload.
研究概览
简要总结
Iron, one of the most common elements in nature and the most abundant transition metal in the body, is readily capable of accepting and donating electrons. This capability makes iron a useful component of various, essential biochemical processes. Despite the essential role of iron, the excess of iron is toxic to the human body. It is critical for the human body to maintain iron balance, since humans have no physiologic mechanism for actively removing iron from the body.
The development of iron overload occurs when iron intake exceeds the body's capacity to safely store the iron in the liver, which is the primary store for iron. Long-term transfusion therapy, a life-giving treatment for patients with intractable chronic anemia is currently the most frequent cause of secondary iron overload.
The mounting evidence regarding the mortality and morbidity due to chronic iron overload in transfusion dependent anaemias has led to the establishment of guidelines that aim the improvement of patient outcomes. Further prospective studies are warranted in order to assess the impact of iron overload in patients with acquired anaemias.
In this study, non-invasive R2- and T2*-MRI techniques were applied to the liver and the heart, respectively, to complement the primary variable (serum ferritin) assessed in patients with various transfusion-dependent anaemias. The main objective of this study was to assess the prevalence and severity of cardiac and liver siderosis in patients with transfusional siderosis. This study was also aim to establish possible correlations between cardiac and liver iron levels with clinical effects in patients with different transfusion-dependent anaemias. Patients were eligible for enrollment irrespective of receiving chelation therapy or not (and irrespective of the chelating agent used).
详细描述
This study was designed to collect information about a large cohort of patients with anaemias including MDS, aplastic anemia, Diamond-Blackfan, myeloproliferative disorder, as well as haemoglobinopathies (e.g. thalassaemia major, SCD) or other anaemias requiring chronic red blood cell transfusions.
Clinical data was collected retrospectively (if available), unless specified by this protocol (e.g. serum ferritin within less than one month prior to enrollment). All assessments required for this protocol were performed after the patient informed consent is signed. The data was gathered by all study centers and was combined in one central database.
Data was recorded using an electronic case report form (eCRF) at each study site. Adverse events and serious adverse events were recorded for all patients from the date of signed patient informed consent until the MRI tests are performed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Confirmed clinical diagnosis of one of the following disease states:
- •Myelodysplastic syndromes,
- •Thalassaemia major, 3.Other anaemias (e.g. NTDT, SCD, Diamond-Blackfan anaemia, aplastic anaemia, myeloproliferative disease)
- •Lifetime history of at least 20 units of red blood cell transfusions AND serum ferritin level > 500 ng/ml; patients with NTDT are not required to have a minimum of 20 units of red blood cell transfusions, but must have serum ferritin level > 300 ng/ml (serum ferritin for all patients must be measured up to 1 month prior to enrollment)
- •Written informed consent obtained prior to any procedure required by this protocol
排除标准
- •Any condition that does not allow the MRI test to be performed:
- •Cardiac pacemaker,
- •Ferromagnetic metal implants other than those approved as safe for use in MR scanners (Example: some types of aneurysm clips, shrapnel),
- •Obesity (exceeding the equipment limits),
- •Patients who are claustrophobic to MR Women who are pregnant Unwillingness or being unable to give consent
结局指标
主要结局
Percentage of Participants With Cardiac and Liver Iron Overload.
时间窗: 2 months
Hepatic iron overload (liver siderosis) and cardiac iron overload (cardiac siderosis) in patients with transfusional siderosis (Myelodysplastic syndrome (MDS), thalassaemia major, non-transfusion-dependent thalassaemia (NTDT) and other anaemias) were measured using MRI (R2 by FerriScan and T2\*, respectively).
Cardiac Siderosis Severity
时间窗: 2 months
Cardiac siderosis severity was measured by MRI (T2\*). The severity grade of siderosis was tiered in 3 levels: mild (T2\* \>= 20ms), moderate (T2\* from 10 to 20ms), and severe (T2\* \<10ms). Mild cardiac siderosis, by the definitions used in this study, were equivalent to not having cardiac siderosis. Values were compared to published thresholds of iron overload to determine severity of transfusion siderosis in the participant population studied.
次要结局
- Comparison of T2* Levels to Evaluate the Severity of Iron Overload Due to Transfusion Therapy in Chelation-naïve and Chelation-treated Participant Subgroups(2 months)
- Comparison of Liver Iron Concentration (LIC) Levels to Evaluate Iron Overload Due to Transfusion Therapy in Chelation-naïve and Chelation-treated Participant Subgroups(2 months)
- Mean Serum Ferritin According to the Presence or Absence of Retrospective Cardiac Events(12 months - retrospective)
- Mean Serum Ferritin According to the Presence or Absence of Retrospective Hepatic Events(12 months - retrospective)
- Mean Cardiac T2* According to the Presence or Absence of Retrospective Cardiac Events(12 months - retrospective)
- Mean LIC According to the Presence or Absence of Retrospective Hepatic Events(12 months - retrospective)
- Mean Blood Magnetic Susceptibility (BMS)(1 month)
- Percentage of Participants Transfused With Erythrocytes(12 months - retrospective)
- Percentage of Participants With Time Since Most Recent Transfuison of <7 Days, 7 to < 14 Days, 14 to < 30 Days, 30 to < 60 Days or >= 60 Days(12 months - retrospective)
- Mean Number of Erythrocyte Units Transfused in Last 12 Months(12 months - retrospective)
- Mean Quality of Life (QOL) Scores(1 month)
- Percentage of Participants With Low Medium or High Adherence to Iron Chelator Therapy(1 month)
- Investigator Treatment Decisions Based on MRI Results(2 months)