Phase 4
N=243
An Epidemiological Study to Assess Iron Overload Using MRI in Patients With Transfusional Siderosis (TIMES Study)
Thalassemia, Non-transfusional-dependent Thalassemia (NTDT), Myeloplastic Dysplasia (MDS), Other Anemia
Bottom Line
View on ClinicalTrials.gov: NCT01736540 ↗Enrolled (actual)
243
Serious AEs
4.9%
Results posted
Sep 2016
Primary outcome: Primary: Percentage of Participants With Cardiac and Liver Iron Overload. — 10; 22; 4; 0 Percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- MRI scan (Device)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- May 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Cardiac and Liver Iron Overload. |
10; 22; 4; 0; 3; 48 | — |
| PRIMARY Cardiac Siderosis Severity |
89.9; 77.6; 95.7; 100.0; 95.4; 4.4 | — |
| SECONDARY Comparison of T2* Levels to Evaluate the Severity of Iron Overload Due to Transfusion Therapy in Chelation-naïve and Chelation-treated Participant Subgroups |
30.2; 23.95; 30.13; 32.69; 30.76; 32.55 | — |
| SECONDARY Comparison of Liver Iron Concentration (LIC) Levels to Evaluate Iron Overload Due to Transfusion Therapy in Chelation-naïve and Chelation-treated Participant Subgroups |
11.30; 8.09; 10.84; 12.38; 12.28; 8.73 | — |
| SECONDARY Mean Serum Ferritin According to the Presence or Absence of Retrospective Cardiac Events |
2153.6; 2150.2 | — |
| SECONDARY Mean Serum Ferritin According to the Presence or Absence of Retrospective Hepatic Events |
3302.8; 2124.1 | — |
| SECONDARY Mean Cardiac T2* According to the Presence or Absence of Retrospective Cardiac Events |
1.546; 1.445 | — |
| SECONDARY Mean LIC According to the Presence or Absence of Retrospective Hepatic Events |
17.51; 10.08 | — |
| SECONDARY Mean Blood Magnetic Susceptibility (BMS) |
-6.18 | — |
| SECONDARY Percentage of Participants Transfused With Erythrocytes |
95.0; 100.0; 100.0; 36.8; 100.0 | — |
| SECONDARY 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 |
43.1; 72.8; 31.0; 14.3; 22.7; 12.9 | — |
| SECONDARY Mean Number of Erythrocyte Units Transfused in Last 12 Months |
33.3; 41.4; 34.7; 8.4; 24.8 | — |
| SECONDARY Mean Quality of Life (QOL) Scores |
43.10; 49.79; 35.67; 49.37; 41.56; 42.54 | — |
| SECONDARY Percentage of Participants With Low Medium or High Adherence to Iron Chelator Therapy |
27.7; 32.1; 11.8; 75.0; 28.0; 61.7 | — |
| SECONDARY Investigator Treatment Decisions Based on MRI Results |
42.4; 57.6 | — |
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).
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
Data sourced from ClinicalTrials.gov (NCT01736540). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.