Thalassemia, NTDT, MDS, MF, Other Anemia Clinical Trial
Official title:
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).
| Status | Completed |
| Enrollment | 228 |
| Est. completion date | May 2015 |
| Est. primary completion date | May 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
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 |
N/A
| Country | Name | City | State |
|---|---|---|---|
| Australia | Novartis Investigative Site | Adelaide | South Australia |
| Australia | Novartis Investigative Site | Bedford Park | South Australia |
| Australia | Novartis Investigative Site | Camperdown | New South Wales |
| Australia | Novartis Investigative Site | East Bentleigh | Victoria |
| Australia | Novartis Investigative Site | Hobart | Tasmania |
| Australia | Novartis Investigative Site | Kogarah | New South Wales |
| Australia | Novartis Investigative Site | Liverpool | New South Wales |
| Australia | Novartis Investigative Site | Nedlands | Western Australia |
| Australia | Novartis Investigative Site | Perth | Western Australia |
| Australia | Novartis Investigative Site | South Brisbane | Queensland |
| Australia | Novartis Investigative Site | St Leonards | New South Wales |
| Australia | Novartis Investigative Site | Wollongong | New South Wales |
| Australia | Novartis Investigative Site | Woolloongabba | Queensland |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
Australia,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Prevalence and severity of liver and cardiac iron overload in patients with transfusional siderosis (MDS, thalassaemia major and other anaemias). | 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. | 12 months - retrospective | No |
| Secondary | Measurement of iron overload due to transfusion therapy comparing chelation-naïve and chelation-treated patient subgroups. | 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). | 12 months - retrospective | No |
| Secondary | 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). | 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). | 12 months | No |
| Secondary | Relationship between serum ferritin, cardiac and liver iron with cardiac and hepatic events. | The relationship between serum ferritin, cardiac and liver iron with cardiac and hepatic events will be assessed all patient subgroups. | 12 months - retrospective | No |
| Secondary | Relationship between BMS and cardiac T2*. | Relationship between BMS and cardiac T2* will be assessed comparing all patient groups. | 1 month | No |
| Secondary | Haematologic parameters and transfusion requirement in patients with acquired anaemias with history of receiving chelation therapy. | 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. | 12 months - retrospective | No |
| Secondary | Quality of life and different disease states, levels of iron overload and different chelation regimens. | Quality of life will be assessed comparing different disease states, levels of iron overload and different chelation regimens. | 1 month | No |
| Secondary | Adherence of patients according to different chelation regimens. | Adherence of patients according to different chelation regimens (adherence questionnaire will only be recorded for patients receiving chelating agents). | 1 month | No |
| Secondary | Treatment decisions based on MRI results. | 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. | 1 month | No |