An Epidemiological Study to Assess Iron Overload Using MRI in Patients With Transfusional Siderosis (TIMES Study)
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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. |
Device: MRI scan
MRI was used to measure both liver and cardiac iron loading (R2 by FerriScan and T2*, respectively).
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Cardiac and Liver Iron Overload. [2 months]
Hepatic iron overload (liver siderosis) and cardiac iron overload (cardiac siderosis) in patients with transfusional siderosis (Myelodysplastic syndrome (MDS), thalassaemia major, non-transfusion-dependent thalassaemia (NTDT) and other anaemias) were measured using MRI (R2 by FerriScan and T2*, respectively).
- Cardiac Siderosis Severity [2 months]
Cardiac siderosis severity was measured by MRI (T2*). The severity grade of siderosis was tiered in 3 levels: mild (T2* >= 20ms), moderate (T2* from 10 to 20ms), and severe (T2* <10ms). Mild cardiac siderosis, by the definitions used in this study, were equivalent to not having cardiac siderosis. Values were compared to published thresholds of iron overload to determine severity of transfusion siderosis in the participant population studied.
Secondary Outcome Measures
- Comparison of T2* Levels to Evaluate the Severity of Iron Overload Due to Transfusion Therapy in Chelation-naïve and Chelation-treated Participant Subgroups [2 months]
Iron overload due to transfusion therapy was assessed based on chelation status of each participant (i.e. minimally exposed to chelator treatment and chelation-treated patient subgroups).
- Comparison of Liver Iron Concentration (LIC) Levels to Evaluate Iron Overload Due to Transfusion Therapy in Chelation-naïve and Chelation-treated Participant Subgroups [2 months]
Iron overload due to transfusion therapy was assessed based on chelation status of each participant (i.e. minimally exposed to chelator treatment and chelation-treated patient subgroups). The mean data presented are mean estimates of log transformed data.
- Mean Serum Ferritin According to the Presence or Absence of Retrospective Cardiac Events [12 months - retrospective]
Mean serum ferritin according to the presence or absence of cardiac events was assessed for all participant subgroups.
- Mean Serum Ferritin According to the Presence or Absence of Retrospective Hepatic Events [12 months - retrospective]
Mean serum ferritin according to the presence or absence of hepatic events was assessed for all participant subgroups.
- Mean Cardiac T2* According to the Presence or Absence of Retrospective Cardiac Events [12 months - retrospective]
Mean cardiac T2* according to the presence or absence of cardiac events was assessed for all participant subgroups. The mean data presented are mean estimates of log transformed data.
- Mean LIC According to the Presence or Absence of Retrospective Hepatic Events [12 months - retrospective]
Mean LIC according to the presence or absence of hepatic events was assessed for all participant subgroups.
- Mean Blood Magnetic Susceptibility (BMS) [1 month]
Blood samples were collected to assess BMS. The measurement represents absolute magnetic susceptibility at 1 month. Whole blood magnetic susceptibility was calculated by the addition of the dry weight susceptibility and the contribution of the water driven from the sample.
- Percentage of Participants Transfused With Erythrocytes [12 months - retrospective]
Transfusion requirement in participants with acquired anaemias with history of receiving chelation therapy was assessed.
- 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 [12 months - retrospective]
Transfusion requirement in participants with acquired anaemias with history of receiving chelation therapy was assessed.
- Mean Number of Erythrocyte Units Transfused in Last 12 Months [12 months - retrospective]
Transfusion requirement in participants with acquired anaemias with history of receiving chelation therapy was assessed.
- Mean Quality of Life (QOL) Scores [1 month]
Quality of life was assessed using the Short Form 36 (SF-36) Health Survey. The SF-36 consists of 8 sub-scales: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning and mental health. The raw sores of the 8 scales are transformed to a 0 - 100 scale where 0 indicates maximum disability and 100 indicates no disability. There also are two physical and mental health summary measures. Each summary measure is the mean average of the 4 associated sub-scale scores. The range for each summary measure is 0 to 100 where 0 represents maximum disability and 100 represents no disability.
- Percentage of Participants With Low Medium or High Adherence to Iron Chelator Therapy [1 month]
Adherence of participants was assessed using an adherence questionnaire. Adherence questionnaires were completed only by participants who received chelating agents. Participants answered yes or no to 6 statements such as "Forgot to take pills". Based on the responses to these questions, adherence was classified as low, medium or high.
- Investigator Treatment Decisions Based on MRI Results [2 months]
Treatment decisions were recorded after the investigator evaluated the MRI results, in order to assess the impact of such diagnostic test on the overall clinical management of participants with iron overload. Investigators answered the following question: "Since the MRI scan, have you changed or are planning to change the management of iron in your subject?".
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Camperdown | New South Wales | Australia | 2050 |
| 2 | Novartis Investigative Site | Kogarah | New South Wales | Australia | 2217 |
| 3 | Novartis Investigative Site | Liverpool | New South Wales | Australia | 2170 |
| 4 | Novartis Investigative Site | St Leonards | New South Wales | Australia | 2065 |
| 5 | Novartis Investigative Site | Wollongong | New South Wales | Australia | 2500 |
| 6 | Novartis Investigative Site | South Brisbane | Queensland | Australia | 4101 |
| 7 | Novartis Investigative Site | Woolloongabba | Queensland | Australia | 4102 |
| 8 | Novartis Investigative Site | Adelaide | South Australia | Australia | 5000 |
| 9 | Novartis Investigative Site | Bedford Park | South Australia | Australia | 5042 |
| 10 | Novartis Investigative Site | Hobart | Tasmania | Australia | 7000 |
| 11 | Novartis Investigative Site | East Bentleigh | Victoria | Australia | 3165 |
| 12 | Novartis Investigative Site | Nedlands | Western Australia | Australia | 6009 |
| 13 | Novartis Investigative Site | Perth | Western Australia | Australia | 6000 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CICL670AAU05
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Magnetic Resonance Imaging (MRI) |
|---|---|
| Arm/Group Description | All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload. |
| Period Title: Overall Study | |
| STARTED | 243 |
| COMPLETED | 228 |
| NOT COMPLETED | 15 |
Baseline Characteristics
| Arm/Group Title | Magnetic Resonance Imaging (MRI) |
|---|---|
| Arm/Group Description | All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload. |
| Overall Participants | 243 |
| Age (Years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [Years] |
52.8
(20.92)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
109
44.9%
|
| Male |
134
55.1%
|
Outcome Measures
| Title | Percentage of Participants With Cardiac and Liver Iron Overload. |
|---|---|
| Description | Hepatic iron overload (liver siderosis) and cardiac iron overload (cardiac siderosis) in patients with transfusional siderosis (Myelodysplastic syndrome (MDS), thalassaemia major, non-transfusion-dependent thalassaemia (NTDT) and other anaemias) were measured using MRI (R2 by FerriScan and T2*, respectively). |
| Time Frame | 2 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only participants with valid T2* by MRI and valid liver iron concentration (LIC) by MRI were included for the cardiac siderosis and liver siderosis analyses, respectively. |
| Arm/Group Title | Magnetic Resonance Imaging (MRI) | Thalassemia Major | Melodysplastic Syndrome (MDS) | Non-transfusion-dependent Anaemia (NTDT) | Other Anaemias |
|---|---|---|---|---|---|
| Arm/Group Description | All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload. | Subset of overall participants with thalassemia major | Subset of overall participants with MDS | Subset of overall participants with NTDT | Subset of overall participants with other types of anaemia |
| Measure Participants | 228 | 76 | 69 | 18 | 65 |
| Cardiac |
10
4.1%
|
22
NaN
|
4
NaN
|
0
NaN
|
3
NaN
|
| Liver |
48
19.8%
|
33
NaN
|
55
NaN
|
50
NaN
|
57
NaN
|
| Title | Cardiac Siderosis Severity |
|---|---|
| Description | Cardiac siderosis severity was measured by MRI (T2*). The severity grade of siderosis was tiered in 3 levels: mild (T2* >= 20ms), moderate (T2* from 10 to 20ms), and severe (T2* <10ms). Mild cardiac siderosis, by the definitions used in this study, were equivalent to not having cardiac siderosis. Values were compared to published thresholds of iron overload to determine severity of transfusion siderosis in the participant population studied. |
| Time Frame | 2 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only participants with valid T2* by MRI were included in the analysis. |
| Arm/Group Title | Magnetic Resonance Imaging (MRI) | Thalassemia Major | Melodysplastic Syndrome (MDS) | Non-transfusion-dependent Anaemia (NTDT) | Other Anaemias |
|---|---|---|---|---|---|
| Arm/Group Description | All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload. | Subset of overall participants with thalassemia major | Subset of overall participants with MDS | Subset of overall participants with NTDT | Subset of overall participants with other types of anaemia |
| Measure Participants | 228 | 76 | 69 | 18 | 65 |
| None |
89.9
37%
|
77.6
NaN
|
95.7
NaN
|
100.0
NaN
|
95.4
NaN
|
| Moderate |
4.4
1.8%
|
11.8
NaN
|
0.0
NaN
|
0.0
NaN
|
1.5
NaN
|
| Severe |
5.7
2.3%
|
10.5
NaN
|
4.3
NaN
|
0.0
NaN
|
3.1
NaN
|
| Title | Comparison of T2* Levels to Evaluate the Severity of Iron Overload Due to Transfusion Therapy in Chelation-naïve and Chelation-treated Participant Subgroups |
|---|---|
| Description | Iron overload due to transfusion therapy was assessed based on chelation status of each participant (i.e. minimally exposed to chelator treatment and chelation-treated patient subgroups). |
| Time Frame | 2 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only participants with valid T2* by MRI were included in the analysis. |
| Arm/Group Title | Magnetic Resonance Imaging (MRI) | Thalassemia Major | Melodysplastic Syndrome (MDS) | Non-transfusion-dependent Anaemia (NTDT) | Other Anaemias |
|---|---|---|---|---|---|
| Arm/Group Description | All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload. | Subset of overall participants with thalassemia major | Subset of overall participants with MDS | Subset of overall participants with NTDT | Subset of overall participants with other types of anaemia |
| Measure Participants | 228 | 76 | 69 | 18 | 65 |
| Overall (n=228,76,69,18,65) |
30.2
|
23.95
|
30.13
|
32.69
|
30.76
|
| Chelation naïve/minimally exposed(n=75,0,27,11,37) |
32.55
|
NA
|
32.05
|
32.95
|
32.66
|
| Chelator exposed (n=153,76,42,7,28) |
28.25
|
23.95
|
28.32
|
32.43
|
28.96
|
| Title | Comparison of Liver Iron Concentration (LIC) Levels to Evaluate Iron Overload Due to Transfusion Therapy in Chelation-naïve and Chelation-treated Participant Subgroups |
|---|---|
| Description | Iron overload due to transfusion therapy was assessed based on chelation status of each participant (i.e. minimally exposed to chelator treatment and chelation-treated patient subgroups). The mean data presented are mean estimates of log transformed data. |
| Time Frame | 2 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only participants with valid LIC by MRI were included in the analysis. |
| Arm/Group Title | Magnetic Resonance Imaging (MRI) | Thalassemia Major | Melodysplastic Syndrome (MDS) | Non-transfusion-dependent Anaemia (NTDT) | Other Anaemias |
|---|---|---|---|---|---|
| Arm/Group Description | All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload. | Subset of overall participants with thalassemia major | Subset of overall participants with MDS | Subset of overall participants with NTDT | Subset of overall participants with other types of anaemia |
| Measure Participants | 228 | 76 | 69 | 18 | 65 |
| Overall (n=228,76,69,18,65) |
11.30
|
8.09
|
10.84
|
12.38
|
12.28
|
| Chelation naïve/minimally exposed(n=75,0,27,11,37) |
8.73
|
NA
|
10.28
|
5.00
|
10.92
|
| Chelator exposed (n=153,76,42,7,28) |
13.22
|
8.09
|
11.40
|
19.76
|
13.64
|
| Title | Mean Serum Ferritin According to the Presence or Absence of Retrospective Cardiac Events |
|---|---|
| Description | Mean serum ferritin according to the presence or absence of cardiac events was assessed for all participant subgroups. |
| Time Frame | 12 months - retrospective |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with serum ferritin values and previous cardiac events data were included in the analysis. |
| Arm/Group Title | Magnetic Resonance Imaging (MRI) |
|---|---|
| Arm/Group Description | All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload. |
| Measure Participants | 238 |
| Cardiac event in past 12 months = yes (n=12) |
2153.6
(1878.6)
|
| Cardiac event in past 12 months = no (n=226) |
2150.2
(1914.5)
|
| Title | Mean Serum Ferritin According to the Presence or Absence of Retrospective Hepatic Events |
|---|---|
| Description | Mean serum ferritin according to the presence or absence of hepatic events was assessed for all participant subgroups. |
| Time Frame | 12 months - retrospective |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with serum ferritin values and previous hepatic events data were included in the analysis. |
| Arm/Group Title | Magnetic Resonance Imaging (MRI) |
|---|---|
| Arm/Group Description | All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload. |
| Measure Participants | 239 |
| Hepatic event in the past 12 months = yes (n=8) |
3302.8
(2684.3)
|
| Hepatic event in the past 12 months = no (n=231) |
2124.1
(1879.2)
|
| Title | Mean Cardiac T2* According to the Presence or Absence of Retrospective Cardiac Events |
|---|---|
| Description | Mean cardiac T2* according to the presence or absence of cardiac events was assessed for all participant subgroups. The mean data presented are mean estimates of log transformed data. |
| Time Frame | 12 months - retrospective |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with valid T2* by MRI results were included in the analysis. |
| Arm/Group Title | Magnetic Resonance Imaging (MRI) |
|---|---|
| Arm/Group Description | All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload. |
| Measure Participants | 228 |
| Cardiac event in past 12 months = yes (n=12) |
1.546
(0.0979)
|
| Cardiac event in the past 12 months = no (n=226) |
1.445
(0.2188)
|
| Title | Mean LIC According to the Presence or Absence of Retrospective Hepatic Events |
|---|---|
| Description | Mean LIC according to the presence or absence of hepatic events was assessed for all participant subgroups. |
| Time Frame | 12 months - retrospective |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with LIC by MRI were included in the analysis. |
| Arm/Group Title | Magnetic Resonance Imaging (MRI) |
|---|---|
| Arm/Group Description | All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload. |
| Measure Participants | 228 |
| Hepatic event in past 12 months = yes (n=7) |
17.51
(15.292)
|
| Hepatic event in past 12 months = no (n=221) |
10.08
(10.950)
|
| Title | Mean Blood Magnetic Susceptibility (BMS) |
|---|---|
| Description | Blood samples were collected to assess BMS. The measurement represents absolute magnetic susceptibility at 1 month. Whole blood magnetic susceptibility was calculated by the addition of the dry weight susceptibility and the contribution of the water driven from the sample. |
| Time Frame | 1 month |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with BMS values were analyzed. |
| Arm/Group Title | Magnetic Resonance Imaging (MRI) |
|---|---|
| Arm/Group Description | All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload. |
| Measure Participants | 233 |
| Mean (Standard Deviation) [emu/g wet wt/Oe] |
-6.18
(0.147)
|
| Title | Percentage of Participants Transfused With Erythrocytes |
|---|---|
| Description | Transfusion requirement in participants with acquired anaemias with history of receiving chelation therapy was assessed. |
| Time Frame | 12 months - retrospective |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a erythrocyte transfusion history were included in the analysis. |
| Arm/Group Title | Magnetic Resonance Imaging (MRI) | Thalassemia Major | Melodysplastic Syndrome (MDS) | Non-transfusion-dependent Anaemia (NTDT) | Other Anaemias |
|---|---|---|---|---|---|
| Arm/Group Description | All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload. | Subset of overall participants with thalassemia major | Subset of overall participants with MDS | Subset of overall participants with NTDT | Subset of overall participants with other types of anaemia |
| Measure Participants | 241 | 81 | 73 | 19 | 68 |
| Number [Percentage of participants] |
95.0
39.1%
|
100.0
NaN
|
100.0
NaN
|
36.8
NaN
|
100.0
NaN
|
| Title | 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 |
|---|---|
| Description | Transfusion requirement in participants with acquired anaemias with history of receiving chelation therapy was assessed. |
| Time Frame | 12 months - retrospective |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with data on time since their most recent transfusion were included in the analysis. |
| Arm/Group Title | Magnetic Resonance Imaging (MRI) | Thalassemia Major | Melodysplastic Syndrome (MDS) | Non-transfusion-dependent Anaemia (NTDT) | Other Anaemias |
|---|---|---|---|---|---|
| Arm/Group Description | All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload. | Subset of overall participants with thalassemia major | Subset of overall participants with MDS | Subset of overall participants with NTDT | Subset of overall participants with other types of anaemia |
| Measure Participants | 241 | 81 | 68 | 19 | 65 |
| < 7 days |
43.1
17.7%
|
72.8
NaN
|
31.0
NaN
|
14.3
NaN
|
22.7
NaN
|
| 7 - < 14 days |
12.9
5.3%
|
2.5
NaN
|
28.2
NaN
|
14.3
NaN
|
9.1
NaN
|
| 14 - < 30 days |
20.0
8.2%
|
22.2
NaN
|
14.1
NaN
|
0.0
NaN
|
25.8
NaN
|
| 30 - < 60 days |
5.8
2.4%
|
2.5
NaN
|
9.9
NaN
|
14.3
NaN
|
4.5
NaN
|
| >= 60 days |
18.2
7.5%
|
0.0
NaN
|
16.9
NaN
|
57.1
NaN
|
37.9
NaN
|
| Title | Mean Number of Erythrocyte Units Transfused in Last 12 Months |
|---|---|
| Description | Transfusion requirement in participants with acquired anaemias with history of receiving chelation therapy was assessed. |
| Time Frame | 12 months - retrospective |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with 'number of units transfused' data were included in the analysis. |
| Arm/Group Title | Magnetic Resonance Imaging (MRI) | Thalassemia Major | Melodysplastic Syndrome (MDS) | Non-transfusion-dependent Anaemia (NTDT) | Other Anaemias |
|---|---|---|---|---|---|
| Arm/Group Description | All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload. | Subset of overall participants with thalassemia major | Subset of overall participants with MDS | Subset of overall participants with NTDT | Subset of overall participants with other types of anaemia |
| Measure Participants | 228 | 81 | 72 | 7 | 68 |
| Mean (Standard Deviation) [number of units transfused] |
33.3
(21.0)
|
41.4
(9.5)
|
34.7
(25.6)
|
8.4
(12.2)
|
24.8
(21.5)
|
| Title | Mean Quality of Life (QOL) Scores |
|---|---|
| Description | Quality of life was assessed using the Short Form 36 (SF-36) Health Survey. The SF-36 consists of 8 sub-scales: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning and mental health. The raw sores of the 8 scales are transformed to a 0 - 100 scale where 0 indicates maximum disability and 100 indicates no disability. There also are two physical and mental health summary measures. Each summary measure is the mean average of the 4 associated sub-scale scores. The range for each summary measure is 0 to 100 where 0 represents maximum disability and 100 represents no disability. |
| Time Frame | 1 month |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only participants with data for each subscale were included in the analysis for that subscale. |
| Arm/Group Title | Magnetic Resonance Imaging (MRI) | Thalassemia Major | Melodysplastic Syndrome (MDS) | Non-transfusion-dependent Anaemia (NTDT) | Other Anaemias |
|---|---|---|---|---|---|
| Arm/Group Description | All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload. | Subset of overall participants with thalassemia major | Subset of overall participants with MDS | Subset of overall participants with NTDT | Subset of overall participants with other types of anaemia |
| Measure Participants | 243 | 81 | 74 | 20 | 68 |
| Physical functioning |
43.10
(11.471)
|
49.79
(9.144)
|
35.67
(9.791)
|
49.37
(7.576)
|
41.56
(11.139)
|
| Role physical |
42.54
(10.895)
|
49.51
(8.836)
|
36.71
(9.462)
|
46.46
(8.717)
|
39.44
(10.229)
|
| Bodily pain |
48.41
(10.969)
|
50.48
(11.084)
|
45.52
(10.750)
|
54.66
(7.773)
|
47.60
(10.815)
|
| General health |
41.65
(9.909)
|
44.82
(9.365)
|
39.48
(9.595)
|
43.23
(8.893)
|
39.80
(10.239)
|
| Vitality |
45.59
(10.267)
|
50.18
(9.277)
|
42.41
(9.190)
|
48.95
(8.424)
|
42.67
(10.757)
|
| Social functioning |
44.99
(11.075)
|
48.98
(9.869)
|
42.37
(10.486)
|
46.43
(9.905)
|
42.67
(12.043)
|
| Role emotional |
43.83
(12.977)
|
48.99
(11.236)
|
40.11
(13.101)
|
47.03
(10.552)
|
40.89
(13.320)
|
| Mental health |
47.84
(11.149)
|
50.09
(11.240)
|
46.69
(9.495)
|
48.74
(9.846)
|
46.12
(12.632)
|
| Physical component summary |
43.48
(9.808)
|
48.75
(7.809)
|
37.55
(8.748)
|
50.34
(6.392)
|
41.93
(9.524)
|
| Mental component summary |
46.76
(11.622)
|
49.58
(10.354)
|
45.91
(10.349)
|
47.47
(10.832)
|
44.08
(13.822)
|
| Title | Percentage of Participants With Low Medium or High Adherence to Iron Chelator Therapy |
|---|---|
| Description | Adherence of participants was assessed using an adherence questionnaire. Adherence questionnaires were completed only by participants who received chelating agents. Participants answered yes or no to 6 statements such as "Forgot to take pills". Based on the responses to these questions, adherence was classified as low, medium or high. |
| Time Frame | 1 month |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who were on iron chelator therapy at screening, and had answered at least one question on the questionnaire and had sufficient information to score the questionnaire, were included in the analysis. |
| Arm/Group Title | Magnetic Resonance Imaging (MRI) | Thalassemia Major | Melodysplastic Syndrome (MDS) | Non-transfusion-dependent Anaemia (NTDT) | Other Anaemias |
|---|---|---|---|---|---|
| Arm/Group Description | All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload. | Subset of overall participants with thalassemia major | Subset of overall participants with MDS | Subset of overall participants with NTDT | Subset of overall participants with other types of anaemia |
| Measure Participants | 141 | 78 | 34 | 4 | 25 |
| Low |
27.7
11.4%
|
32.1
NaN
|
11.8
NaN
|
75.0
NaN
|
28.0
NaN
|
| Medium |
61.7
25.4%
|
57.7
NaN
|
73.5
NaN
|
25.0
NaN
|
64.0
NaN
|
| High |
10.6
4.4%
|
10.3
NaN
|
14.7
NaN
|
0.0
NaN
|
8.0
NaN
|
| Title | Investigator Treatment Decisions Based on MRI Results |
|---|---|
| Description | Treatment decisions were recorded after the investigator evaluated the MRI results, in order to assess the impact of such diagnostic test on the overall clinical management of participants with iron overload. Investigators answered the following question: "Since the MRI scan, have you changed or are planning to change the management of iron in your subject?". |
| Time Frame | 2 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants, for whom treatment decision questionnaire results were provided and for whom MRI results were available, were included in the analysis. |
| Arm/Group Title | Magnetic Resonance Imaging (MRI) |
|---|---|
| Arm/Group Description | All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload. |
| Measure Participants | 229 |
| Answer = yes |
42.4
17.4%
|
| Answer = no |
57.6
23.7%
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Thalassaemia Major | Myelodysplastic Syndrome (MDS) | Other Anaemia | Non-transfusion-dependent Anaemia (NTDT) | ||||
| Arm/Group Description | Subset of overall participants with thalassemia major | Subset of overall participants with MDS | Subset of overall participants with other types of anaemias | Subset of overall participants with NTDT | ||||
All Cause Mortality |
||||||||
| Thalassaemia Major | Myelodysplastic Syndrome (MDS) | Other Anaemia | Non-transfusion-dependent Anaemia (NTDT) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Thalassaemia Major | Myelodysplastic Syndrome (MDS) | Other Anaemia | Non-transfusion-dependent Anaemia (NTDT) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/81 (2.5%) | 8/74 (10.8%) | 2/68 (2.9%) | 0/20 (0%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Febrile neutropenia | 0/81 (0%) | 1/74 (1.4%) | 2/68 (2.9%) | 0/20 (0%) | ||||
| Thrombocytopenia | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Cardiac disorders | ||||||||
| Angina pectoris | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Eye disorders | ||||||||
| Eye swelling | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Diarrhoea | 0/81 (0%) | 2/74 (2.7%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Rectal haemorrhage | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| General disorders | ||||||||
| Malaise | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Medical device site erosion | 1/81 (1.2%) | 0/74 (0%) | 0/68 (0%) | 0/20 (0%) | ||||
| Medical device site pain | 1/81 (1.2%) | 0/74 (0%) | 0/68 (0%) | 0/20 (0%) | ||||
| Medical device site swelling | 1/81 (1.2%) | 0/74 (0%) | 0/68 (0%) | 0/20 (0%) | ||||
| Pyrexia | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Cholecystitis acute | 1/81 (1.2%) | 0/74 (0%) | 0/68 (0%) | 0/20 (0%) | ||||
| Infections and infestations | ||||||||
| Infection | 1/81 (1.2%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Klebsiella infection | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Nasopharyngitis | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Pneumonia | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Fall | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Investigations | ||||||||
| C-reactive protein increased | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Electrocardiogram QT prolonged | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Platelet count decreased | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Hypokalaemia | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Myelodysplastic syndrome | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Psychiatric disorders | ||||||||
| Anxiety | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Pulmonary oedema | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Thalassaemia Major | Myelodysplastic Syndrome (MDS) | Other Anaemia | Non-transfusion-dependent Anaemia (NTDT) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/81 (8.6%) | 9/74 (12.2%) | 3/68 (4.4%) | 0/20 (0%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/81 (0%) | 1/74 (1.4%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Febrile neutropenia | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Thrombocytopenia | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Cardiac disorders | ||||||||
| Palpitations | 0/81 (0%) | 2/74 (2.7%) | 0/68 (0%) | 0/20 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Hypoacusis | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Eye disorders | ||||||||
| Dry eye | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 0/81 (0%) | 3/74 (4.1%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Abdominal pain upper | 1/81 (1.2%) | 0/74 (0%) | 0/68 (0%) | 0/20 (0%) | ||||
| Constipation | 0/81 (0%) | 1/74 (1.4%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Diarrhoea | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Gastrointestinal disorder | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Nausea | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Proctalgia | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Rectal haemorrhage | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| General disorders | ||||||||
| Asthenia | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Chest pain | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Fatigue | 0/81 (0%) | 2/74 (2.7%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Influenza like illness | 1/81 (1.2%) | 0/74 (0%) | 0/68 (0%) | 0/20 (0%) | ||||
| Injection site reaction | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Oedema | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Oedema peripheral | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Pain | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Pyrexia | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Infections and infestations | ||||||||
| Lower respiratory tract infection | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Pneumonia | 1/81 (1.2%) | 0/74 (0%) | 0/68 (0%) | 0/20 (0%) | ||||
| Respiratory tract infection | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Tonsillitis | 1/81 (1.2%) | 0/74 (0%) | 0/68 (0%) | 0/20 (0%) | ||||
| Upper respiratory tract infection | 2/81 (2.5%) | 0/74 (0%) | 0/68 (0%) | 0/20 (0%) | ||||
| Urinary tract infection | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Viral infection | 1/81 (1.2%) | 0/74 (0%) | 0/68 (0%) | 0/20 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Infusion related reaction | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Investigations | ||||||||
| Heart rate increased | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Dehydration | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Gout | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Hypokalaemia | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Arthritis | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Flank pain | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Pain in extremity | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Nervous system disorders | ||||||||
| Headache | 0/81 (0%) | 2/74 (2.7%) | 0/68 (0%) | 0/20 (0%) | ||||
| Sinus headache | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Psychiatric disorders | ||||||||
| Insomnia | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Sleep disorder | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Haematuria | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnoea | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Epistaxis | 0/81 (0%) | 1/74 (1.4%) | 0/68 (0%) | 0/20 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Pruritus | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
| Vascular disorders | ||||||||
| Hypotension | 0/81 (0%) | 0/74 (0%) | 1/68 (1.5%) | 0/20 (0%) | ||||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis |
| Phone | 862-778-8300 |
- CICL670AAU05