- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01736540
An Epidemiological Study to Assess Iron Overload Using MRI in Patients With Transfusional Siderosis (TIMES Study)
An Epidemiological Study to Assess the Prevalence of Iron Overload Using MRI in Patients With Transfusional Siderosis (TIMES Study)
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).
Study Overview
Status
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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New South Wales
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Camperdown, New South Wales, Australia, 2050
- Novartis Investigative Site
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Kogarah, New South Wales, Australia, 2217
- Novartis Investigative Site
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Liverpool, New South Wales, Australia, 2170
- Novartis Investigative Site
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St Leonards, New South Wales, Australia, 2065
- Novartis Investigative Site
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Wollongong, New South Wales, Australia, 2500
- Novartis Investigative Site
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Queensland
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South Brisbane, Queensland, Australia, 4101
- Novartis Investigative Site
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Woolloongabba, Queensland, Australia, 4102
- Novartis Investigative Site
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South Australia
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Adelaide, South Australia, Australia, 5000
- Novartis Investigative Site
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Bedford Park, South Australia, Australia, 5042
- Novartis Investigative Site
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Tasmania
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Hobart, Tasmania, Australia, 7000
- Novartis Investigative Site
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Victoria
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East Bentleigh, Victoria, Australia, 3165
- Novartis Investigative Site
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Western Australia
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Nedlands, Western Australia, Australia, 6009
- Novartis Investigative Site
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Perth, Western Australia, Australia, 6000
- Novartis Investigative Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥18 years
- Confirmed clinical diagnosis of one of the following disease states: 1. Myelodysplastic syndromes, 2. 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
Exclusion Criteria:
Any condition that does not allow the MRI test to be performed: 1. Cardiac pacemaker, 2. Ferromagnetic metal implants other than those approved as safe for use in MR scanners (Example: some types of aneurysm clips, shrapnel), 3. Obesity (exceeding the equipment limits), 4. Patients who are claustrophobic to MR Women who are pregnant Unwillingness or being unable to give consent
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Magnetic Resonance Imaging (MRI)
All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload.
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MRI was used to measure both liver and cardiac iron loading (R2 by FerriScan and T2*, respectively).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Cardiac and Liver Iron Overload.
Time Frame: 2 months
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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).
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2 months
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Cardiac Siderosis Severity
Time Frame: 2 months
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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.
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2 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Comparison of T2* Levels to Evaluate the Severity of Iron Overload Due to Transfusion Therapy in Chelation-naïve and Chelation-treated Participant Subgroups
Time Frame: 2 months
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Iron overload due to transfusion therapy was assessed based on chelation status of each participant (i.e.
minimally exposed to chelator treatment and chelation-treated patient subgroups).
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2 months
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Comparison of Liver Iron Concentration (LIC) Levels to Evaluate Iron Overload Due to Transfusion Therapy in Chelation-naïve and Chelation-treated Participant Subgroups
Time Frame: 2 months
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Iron overload due to transfusion therapy was assessed based on chelation status of each participant (i.e.
minimally exposed to chelator treatment and chelation-treated patient subgroups).
The mean data presented are mean estimates of log transformed data.
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2 months
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Mean Serum Ferritin According to the Presence or Absence of Retrospective Cardiac Events
Time Frame: 12 months - retrospective
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Mean serum ferritin according to the presence or absence of cardiac events was assessed for all participant subgroups.
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12 months - retrospective
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Mean Serum Ferritin According to the Presence or Absence of Retrospective Hepatic Events
Time Frame: 12 months - retrospective
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Mean serum ferritin according to the presence or absence of hepatic events was assessed for all participant subgroups.
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12 months - retrospective
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Mean Cardiac T2* According to the Presence or Absence of Retrospective Cardiac Events
Time Frame: 12 months - retrospective
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Mean cardiac T2* according to the presence or absence of cardiac events was assessed for all participant subgroups.
The mean data presented are mean estimates of log transformed data.
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12 months - retrospective
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Mean LIC According to the Presence or Absence of Retrospective Hepatic Events
Time Frame: 12 months - retrospective
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Mean LIC according to the presence or absence of hepatic events was assessed for all participant subgroups.
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12 months - retrospective
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Mean Blood Magnetic Susceptibility (BMS)
Time Frame: 1 month
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Blood samples were collected to assess BMS.
The measurement represents absolute magnetic susceptibility at 1 month.
Whole blood magnetic susceptibility was calculated by the addition of the dry weight susceptibility and the contribution of the water driven from the sample.
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1 month
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Percentage of Participants Transfused With Erythrocytes
Time Frame: 12 months - retrospective
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Transfusion requirement in participants with acquired anaemias with history of receiving chelation therapy was assessed.
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12 months - retrospective
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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
Time Frame: 12 months - retrospective
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Transfusion requirement in participants with acquired anaemias with history of receiving chelation therapy was assessed.
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12 months - retrospective
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Mean Number of Erythrocyte Units Transfused in Last 12 Months
Time Frame: 12 months - retrospective
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Transfusion requirement in participants with acquired anaemias with history of receiving chelation therapy was assessed.
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12 months - retrospective
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Mean Quality of Life (QOL) Scores
Time Frame: 1 month
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Quality of life was assessed using the Short Form 36 (SF-36) Health Survey.
The SF-36 consists of 8 sub-scales: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning and mental health.
The raw sores of the 8 scales are transformed to a 0 - 100 scale where 0 indicates maximum disability and 100 indicates no disability.
There also are two physical and mental health summary measures.
Each summary measure is the mean average of the 4 associated sub-scale scores.
The range for each summary measure is 0 to 100 where 0 represents maximum disability and 100 represents no disability.
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1 month
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Percentage of Participants With Low Medium or High Adherence to Iron Chelator Therapy
Time Frame: 1 month
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Adherence of participants was assessed using an adherence questionnaire.
Adherence questionnaires were completed only by participants who received chelating agents.
Participants answered yes or no to 6 statements such as "Forgot to take pills".
Based on the responses to these questions, adherence was classified as low, medium or high.
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1 month
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Investigator Treatment Decisions Based on MRI Results
Time Frame: 2 months
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Treatment decisions were recorded after the investigator evaluated the MRI results, in order to assess the impact of such diagnostic test on the overall clinical management of participants with iron overload.
Investigators answered the following question: "Since the MRI scan, have you changed or are planning to change the management of iron in your subject?".
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2 months
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Respiratory Tract Diseases
- Lung Diseases
- Hematologic Diseases
- Genetic Diseases, Inborn
- Occupational Diseases
- Anemia
- Iron Metabolism Disorders
- Pneumoconiosis
- Lung Diseases, Interstitial
- Lung Injury
- Anemia, Hemolytic, Congenital
- Anemia, Hemolytic
- Hemoglobinopathies
- Iron Overload
- Thalassemia
- Siderosis
Other Study ID Numbers
- CICL670AAU05
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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