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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01736540




Registration number
NCT01736540
Ethics application status
Date submitted
26/11/2012
Date registered
29/11/2012
Date last updated
12/04/2017

Titles & IDs
Public title
An Epidemiological Study to Assess Iron Overload Using MRI in Patients With Transfusional Siderosis (TIMES Study)
Scientific title
An Epidemiological Study to Assess the Prevalence of Iron Overload Using MRI in Patients With Transfusional Siderosis (TIMES Study)
Secondary ID [1] 0 0
CICL670AAU05
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Thalassemia, Non-transfusional-dependent Thalassemia (NTDT), Myeloplastic Dysplasia (MDS), Other Anemia 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Diet and Nutrition 0 0 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - MRI scan

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.


Treatment: Devices: MRI scan
MRI was used to measure both liver and cardiac iron loading (R2 by FerriScan and T2*, respectively).

Intervention code [1] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Cardiac and Liver Iron Overload.
Timepoint [1] 0 0
2 months
Primary outcome [2] 0 0
Cardiac Siderosis Severity
Timepoint [2] 0 0
2 months
Secondary outcome [1] 0 0
Comparison of T2* Levels to Evaluate the Severity of Iron Overload Due to Transfusion Therapy in Chelation-naïve and Chelation-treated Participant Subgroups
Timepoint [1] 0 0
2 months
Secondary outcome [2] 0 0
Comparison of Liver Iron Concentration (LIC) Levels to Evaluate Iron Overload Due to Transfusion Therapy in Chelation-naïve and Chelation-treated Participant Subgroups
Timepoint [2] 0 0
2 months
Secondary outcome [3] 0 0
Mean Serum Ferritin According to the Presence or Absence of Retrospective Cardiac Events
Timepoint [3] 0 0
12 months - retrospective
Secondary outcome [4] 0 0
Mean Serum Ferritin According to the Presence or Absence of Retrospective Hepatic Events
Timepoint [4] 0 0
12 months - retrospective
Secondary outcome [5] 0 0
Mean Cardiac T2* According to the Presence or Absence of Retrospective Cardiac Events
Timepoint [5] 0 0
12 months - retrospective
Secondary outcome [6] 0 0
Mean LIC According to the Presence or Absence of Retrospective Hepatic Events
Timepoint [6] 0 0
12 months - retrospective
Secondary outcome [7] 0 0
Mean Blood Magnetic Susceptibility (BMS)
Timepoint [7] 0 0
1 month
Secondary outcome [8] 0 0
Percentage of Participants Transfused With Erythrocytes
Timepoint [8] 0 0
12 months - retrospective
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
12 months - retrospective
Secondary outcome [10] 0 0
Mean Number of Erythrocyte Units Transfused in Last 12 Months
Timepoint [10] 0 0
12 months - retrospective
Secondary outcome [11] 0 0
Mean Quality of Life (QOL) Scores
Timepoint [11] 0 0
1 month
Secondary outcome [12] 0 0
Percentage of Participants With Low Medium or High Adherence to Iron Chelator Therapy
Timepoint [12] 0 0
1 month
Secondary outcome [13] 0 0
Investigator Treatment Decisions Based on MRI Results
Timepoint [13] 0 0
2 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Other
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Camperdown
Recruitment hospital [2] 0 0
Novartis Investigative Site - Kogarah
Recruitment hospital [3] 0 0
Novartis Investigative Site - Liverpool
Recruitment hospital [4] 0 0
Novartis Investigative Site - St Leonards
Recruitment hospital [5] 0 0
Novartis Investigative Site - Wollongong
Recruitment hospital [6] 0 0
Novartis Investigative Site - South Brisbane
Recruitment hospital [7] 0 0
Novartis Investigative Site - Woolloongabba
Recruitment hospital [8] 0 0
Novartis Investigative Site - Adelaide
Recruitment hospital [9] 0 0
Novartis Investigative Site - Bedford Park
Recruitment hospital [10] 0 0
Novartis Investigative Site - Hobart
Recruitment hospital [11] 0 0
Novartis Investigative Site - East Bentleigh
Recruitment hospital [12] 0 0
Novartis Investigative Site - Nedlands
Recruitment hospital [13] 0 0
Novartis Investigative Site - Perth
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2170 - Liverpool
Recruitment postcode(s) [4] 0 0
2065 - St Leonards
Recruitment postcode(s) [5] 0 0
2500 - Wollongong
Recruitment postcode(s) [6] 0 0
4101 - South Brisbane
Recruitment postcode(s) [7] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [8] 0 0
5000 - Adelaide
Recruitment postcode(s) [9] 0 0
5042 - Bedford Park
Recruitment postcode(s) [10] 0 0
7000 - Hobart
Recruitment postcode(s) [11] 0 0
3165 - East Bentleigh
Recruitment postcode(s) [12] 0 0
6009 - Nedlands
Recruitment postcode(s) [13] 0 0
6000 - Perth

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT01736540
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01736540