Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

An Epidemiological Study to Assess Iron Overload Using MRI in Patients With Transfusional Siderosis (TIMES Study) (MACS1631)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01736540
First received: November 26, 2012
Last updated: May 1, 2014
Last verified: May 2014

November 26, 2012
May 1, 2014
February 2013
September 2014   (final data collection date for primary outcome measure)
Prevalence and severity of liver and cardiac iron overload in patients with transfusional siderosis (MDS, thalassaemia major and other anaemias). [ Time Frame: 12 months - retrospective ] [ Designated as safety issue: No ]
Hepatic and cardiac iron overload in patients with transfusional siderosis (MDS, thalassaemia major and other anaemias) will be measured using MRI to measure both liver and cardiac iron loading (R2 by FerriScan and T2*, respectively). Values will be compared to published thresholds of iron overload to determine severity of transfusion siderosis in the patient population studied.
Same as current
Complete list of historical versions of study NCT01736540 on ClinicalTrials.gov Archive Site
  • Measurement of iron overload due to transfusion therapy comparing chelation-naïve and chelation-treated patient subgroups. [ Time Frame: 12 months - retrospective ] [ Designated as safety issue: No ]
    The severity of iron overload due to transfusion therapy will be assessed based on chelation status of each patient (i.e. chelation-naïve and chelation-treated patient subgroups).
  • Levels of cardiac and liver siderosis in different populations of patients requiring regular blood transfusions (e.g. thalassaemia major vs. NTDT, thalassaemia major vs. MDS). [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Levels of cardiac and liver siderosis will be compared between patient subgroups, according to their primary diagnosis leading to anaemia (e.g. thalassaemia major vs. NTDT, thalassaemia major vs. MDS).
  • Relationship between serum ferritin, cardiac and liver iron with cardiac and hepatic events. [ Time Frame: 12 months - retrospective ] [ Designated as safety issue: No ]
    The relationship between serum ferritin, cardiac and liver iron with cardiac and hepatic events will be assessed all patient subgroups.
  • Relationship between BMS and cardiac T2*. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Relationship between BMS and cardiac T2* will be assessed comparing all patient groups.
  • Haematologic parameters and transfusion requirement in patients with acquired anaemias with history of receiving chelation therapy. [ Time Frame: 12 months - retrospective ] [ Designated as safety issue: No ]
    haematologic parameters and transfusion requirement in patients with acquired anaemias with history of receiving chelation therapy will be assessed, in order to evaluate possible impact of chelation on transfusion independence.
  • Quality of life and different disease states, levels of iron overload and different chelation regimens. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Quality of life will be assessed comparing different disease states, levels of iron overload and different chelation regimens.
  • Adherence of patients according to different chelation regimens. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Adherence of patients according to different chelation regimens (adherence questionnaire will only be recorded for patients receiving chelating agents).
  • Treatment decisions based on MRI results. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Treatment decisions will be recorded after the investigator evaluates the MRI results, in order to assess the impact of such diagnostic test on the overall clinical management of patients with iron overload.
Same as current
Not Provided
Not Provided
 
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 will be 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 is to assess the prevalence and severity of cardiac and liver siderosis in patients with transfusional siderosis. This study will also aim to establish possible correlations between cardiac and liver iron levels with clinical effects in patients with different transfusion-dependent anaemias. Patients will be eligible for enrollment irrespective of receiving chelation therapy or not (and irrespective of the chelating agent used).

This study is 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 will be 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 should be performed after the patient informed consent is signed. The data will be gathered by all study centers and will be combined in one central database.

Data will be recorded using an electronic case report form (eCRF) at each study site. Adverse events and serious adverse events will be recorded for all patients from the date of signed patient informed consent until the MRI tests are performed.

Interventional
Not Provided
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Thalassemia, Non-transfusion Dependent Thalassemia, Myelodysplastic Syndromes, Myelofibrosis, Other Anemia
Radiation: Single arm MRI test
All patients will be subjected to the non-invasive hepatic and cardiac MRI test to measure iron overload.
Single arm MRI test
All patients will be subjected to the non-invasive hepatic and cardiac MRI test to measure iron overload.
Intervention: Radiation: Single arm MRI test
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
250
September 2014
September 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

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

Both
12 Years and older
No
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals
Australia
 
NCT01736540
CICL670AAU05
Yes
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP