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

NCT ID: NCT01736540

Last Updated: 2017-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 243 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2015-05-31

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).

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.

Conditions

Thalassemia, Non-transfusional-dependent Thalassemia (NTDT), Myeloplastic Dysplasia (MDS), Other Anemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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.

Group Type: OTHER

MRI scan

Intervention Type: DEVICE

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

Interventions

MRI scan

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

Intervention Type: DEVICE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Camperdown, New South Wales, Australia

Novartis Investigative Site

Kogarah, New South Wales, Australia

Novartis Investigative Site

Liverpool, New South Wales, Australia

Novartis Investigative Site

St Leonards, New South Wales, Australia

Novartis Investigative Site

Wollongong, New South Wales, Australia

Novartis Investigative Site

South Brisbane, Queensland, Australia

Novartis Investigative Site

Woolloongabba, Queensland, Australia

Novartis Investigative Site

Adelaide, South Australia, Australia

Novartis Investigative Site

Bedford Park, South Australia, Australia

Novartis Investigative Site

Hobart, Tasmania, Australia

Novartis Investigative Site

East Bentleigh, Victoria, Australia

Novartis Investigative Site

Nedlands, Western Australia, Australia

Novartis Investigative Site

Perth, Western Australia, Australia

Countries

Australia

References

Ho PJ, Hiwase D, Ramakrishna R, Viiala N, Solterbeck A, Traficante R, Zor E, Gervasio OL, High LM, Ross DM, Bowden DK. Cardiac and hepatic siderosis in myelodysplastic syndrome, thalassemia and diverse causes of transfusion-dependent anemia: the TIMES study. Hemasphere. 2019 Jun 4;3(3):e224. doi: 10.1097/HS9.0000000000000224. eCollection 2019 Jun.

Reference Type: DERIVED

PMID: 31723837 (View on PubMed)

Other Identifiers

CICL670AAU05

Identifier Type: -

Identifier Source: org_study_id