Trial Outcomes & Findings for An Epidemiological Study to Assess Iron Overload Using MRI in Patients With Transfusional Siderosis (TIMES Study) (NCT NCT01736540)

Last Updated: 2017-04-12

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

243 participants

Primary outcome timeframe

2 months

Results posted on

2017-04-12

Participant Flow

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	243
Overall Study COMPLETED	228
Overall Study NOT COMPLETED	15

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Did not complete scan within 45 days	2
Overall Study Death	1
Overall Study Abnormal test procedure	1
Overall Study Withdrawal by Subject	5
Overall Study Protocol Violation	1
Overall Study Unable to tolerate MRI; claustrophobic	1
Overall Study No show for MRI appointment	1
Overall Study Unable to make MRI appointment	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Magnetic Resonance Imaging (MRI) n=243 Participants All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload.
Age, Continuous	52.8 Years STANDARD_DEVIATION 20.92 • n=5 Participants
Sex: Female, Male Female	109 Participants n=5 Participants
Sex: Female, Male Male	134 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 months

Population: 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.

Outcome measures

Outcome measures
Measure	Magnetic Resonance Imaging (MRI) n=228 Participants All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload.	Thalassemia Major n=76 Participants Subset of overall participants with thalassemia major	Melodysplastic Syndrome (MDS) n=69 Participants Subset of overall participants with MDS	Non-transfusion-dependent Anaemia (NTDT) n=18 Participants Subset of overall participants with NTDT	Other Anaemias n=65 Participants Subset of overall participants with other types of anaemia
Percentage of Participants With Cardiac and Liver Iron Overload. Cardiac	10 Percentage of participants	22 Percentage of participants	4 Percentage of participants	0 Percentage of participants	3 Percentage of participants
Percentage of Participants With Cardiac and Liver Iron Overload. Liver	48 Percentage of participants	33 Percentage of participants	55 Percentage of participants	50 Percentage of participants	57 Percentage of participants

PRIMARY outcome

Timeframe: 2 months

Population: Only participants with valid T2\* by MRI were included in the analysis.

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.

Outcome measures

Outcome measures
Measure	Magnetic Resonance Imaging (MRI) n=228 Participants All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload.	Thalassemia Major n=76 Participants Subset of overall participants with thalassemia major	Melodysplastic Syndrome (MDS) n=69 Participants Subset of overall participants with MDS	Non-transfusion-dependent Anaemia (NTDT) n=18 Participants Subset of overall participants with NTDT	Other Anaemias n=65 Participants Subset of overall participants with other types of anaemia
Cardiac Siderosis Severity None	89.9 Percentage of participants	77.6 Percentage of participants	95.7 Percentage of participants	100.0 Percentage of participants	95.4 Percentage of participants
Cardiac Siderosis Severity Moderate	4.4 Percentage of participants	11.8 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	1.5 Percentage of participants
Cardiac Siderosis Severity Severe	5.7 Percentage of participants	10.5 Percentage of participants	4.3 Percentage of participants	0.0 Percentage of participants	3.1 Percentage of participants

SECONDARY outcome

Timeframe: 2 months

Population: Only participants with valid T2\* by MRI were included in the analysis.

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).

Outcome measures

Outcome measures
Measure	Magnetic Resonance Imaging (MRI) n=228 Participants All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload.	Thalassemia Major n=76 Participants Subset of overall participants with thalassemia major	Melodysplastic Syndrome (MDS) n=69 Participants Subset of overall participants with MDS	Non-transfusion-dependent Anaemia (NTDT) n=18 Participants Subset of overall participants with NTDT	Other Anaemias n=65 Participants Subset of overall participants with other types of anaemia
Comparison of T2* Levels to Evaluate the Severity of Iron Overload Due to Transfusion Therapy in Chelation-naïve and Chelation-treated Participant Subgroups Overall (n=228,76,69,18,65)	30.2 ms Interval 27.62 to 32.62	23.95 ms Interval 21.46 to 26.72	30.13 ms Interval 26.78 to 33.9	32.69 ms Interval 25.94 to 41.19	30.76 ms Interval 27.29 to 34.67
Comparison of T2* Levels to Evaluate the Severity of Iron Overload Due to Transfusion Therapy in Chelation-naïve and Chelation-treated Participant Subgroups Chelation naïve/minimally exposed(n=75,0,27,11,37)	32.55 ms Interval 28.71 to 36.91	NA ms No participants were minimally exposed to chelator treatment.	32.05 ms Interval 26.66 to 38.53	32.95 ms Interval 24.7 to 43.97	32.66 ms Interval 27.91 to 38.22
Comparison of T2* Levels to Evaluate the Severity of Iron Overload Due to Transfusion Therapy in Chelation-naïve and Chelation-treated Participant Subgroups Chelator exposed (n=153,76,42,7,28)	28.25 ms Interval 25.28 to 31.57	23.95 ms Interval 21.46 to 26.72	28.32 ms Interval 24.43 to 32.82	32.43 ms Interval 22.59 to 46.55	28.96 ms Interval 24.17 to 34.7

SECONDARY outcome

Timeframe: 2 months

Population: Only participants with valid LIC by MRI were included in the analysis.

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.

Outcome measures

Outcome measures
Measure	Magnetic Resonance Imaging (MRI) n=228 Participants All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload.	Thalassemia Major n=76 Participants Subset of overall participants with thalassemia major	Melodysplastic Syndrome (MDS) n=69 Participants Subset of overall participants with MDS	Non-transfusion-dependent Anaemia (NTDT) n=18 Participants Subset of overall participants with NTDT	Other Anaemias n=65 Participants Subset of overall participants with other types of anaemia
Comparison of Liver Iron Concentration (LIC) Levels to Evaluate Iron Overload Due to Transfusion Therapy in Chelation-naïve and Chelation-treated Participant Subgroups Overall (n=228,76,69,18,65)	11.30 mg Fe/g Interval 9.42 to 13.17	8.09 mg Fe/g Interval 5.62 to 10.57	10.84 mg Fe/g Interval 8.18 to 13.5	12.38 mg Fe/g Interval 7.16 to 17.59	12.28 mg Fe/g Interval 9.58 to 14.98
Comparison of Liver Iron Concentration (LIC) Levels to Evaluate Iron Overload Due to Transfusion Therapy in Chelation-naïve and Chelation-treated Participant Subgroups Chelation naïve/minimally exposed(n=75,0,27,11,37)	8.73 mg Fe/g Interval 5.9 to 11.56	NA mg Fe/g No participants were minimally exposed.	10.28 mg Fe/g Interval 6.13 to 14.43	5.00 mg Fe/g Interval -1.5 to 11.5	10.92 mg Fe/g Interval 7.37 to 14.47
Comparison of Liver Iron Concentration (LIC) Levels to Evaluate Iron Overload Due to Transfusion Therapy in Chelation-naïve and Chelation-treated Participant Subgroups Chelator exposed (n=153,76,42,7,28)	13.22 mg Fe/g Interval 10.72 to 15.72	8.09 mg Fe/g Interval 5.62 to 10.57	11.40 mg Fe/g Interval 8.07 to 14.72	19.76 mg Fe/g Interval 11.6 to 27.91	13.64 mg Fe/g Interval 9.56 to 17.72

SECONDARY outcome

Timeframe: 12 months - retrospective

Population: Participants with serum ferritin values and previous cardiac events data were included in the analysis.

Mean serum ferritin according to the presence or absence of cardiac events was assessed for all participant subgroups.

Outcome measures

Outcome measures
Measure	Magnetic Resonance Imaging (MRI) n=238 Participants All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload.	Thalassemia Major Subset of overall participants with thalassemia major	Melodysplastic Syndrome (MDS) Subset of overall participants with MDS	Non-transfusion-dependent Anaemia (NTDT) Subset of overall participants with NTDT	Other Anaemias Subset of overall participants with other types of anaemia
Mean Serum Ferritin According to the Presence or Absence of Retrospective Cardiac Events Cardiac event in past 12 months = yes (n=12)	2153.6 ng/mL Standard Deviation 1878.6	—	—	—	—
Mean Serum Ferritin According to the Presence or Absence of Retrospective Cardiac Events Cardiac event in past 12 months = no (n=226)	2150.2 ng/mL Standard Deviation 1914.5	—	—	—	—

SECONDARY outcome

Timeframe: 12 months - retrospective

Population: Participants with serum ferritin values and previous hepatic events data were included in the analysis.

Mean serum ferritin according to the presence or absence of hepatic events was assessed for all participant subgroups.

Outcome measures

Outcome measures
Measure	Magnetic Resonance Imaging (MRI) n=239 Participants All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload.	Thalassemia Major Subset of overall participants with thalassemia major	Melodysplastic Syndrome (MDS) Subset of overall participants with MDS	Non-transfusion-dependent Anaemia (NTDT) Subset of overall participants with NTDT	Other Anaemias Subset of overall participants with other types of anaemia
Mean Serum Ferritin According to the Presence or Absence of Retrospective Hepatic Events Hepatic event in the past 12 months = yes (n=8)	3302.8 ng/mL Standard Deviation 2684.3	—	—	—	—
Mean Serum Ferritin According to the Presence or Absence of Retrospective Hepatic Events Hepatic event in the past 12 months = no (n=231)	2124.1 ng/mL Standard Deviation 1879.2	—	—	—	—

SECONDARY outcome

Timeframe: 12 months - retrospective

Population: Participants with valid T2\* by MRI results were included in the analysis.

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.

Outcome measures

Outcome measures
Measure	Magnetic Resonance Imaging (MRI) n=228 Participants All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload.	Thalassemia Major Subset of overall participants with thalassemia major	Melodysplastic Syndrome (MDS) Subset of overall participants with MDS	Non-transfusion-dependent Anaemia (NTDT) Subset of overall participants with NTDT	Other Anaemias Subset of overall participants with other types of anaemia
Mean Cardiac T2* According to the Presence or Absence of Retrospective Cardiac Events Cardiac event in past 12 months = yes (n=12)	1.546 log10 (ms) Standard Deviation 0.0979	—	—	—	—
Mean Cardiac T2* According to the Presence or Absence of Retrospective Cardiac Events Cardiac event in the past 12 months = no (n=226)	1.445 log10 (ms) Standard Deviation 0.2188	—	—	—	—

SECONDARY outcome

Timeframe: 12 months - retrospective

Population: Participants with LIC by MRI were included in the analysis.

Mean LIC according to the presence or absence of hepatic events was assessed for all participant subgroups.

Outcome measures

Outcome measures
Measure	Magnetic Resonance Imaging (MRI) n=228 Participants All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload.	Thalassemia Major Subset of overall participants with thalassemia major	Melodysplastic Syndrome (MDS) Subset of overall participants with MDS	Non-transfusion-dependent Anaemia (NTDT) Subset of overall participants with NTDT	Other Anaemias Subset of overall participants with other types of anaemia
Mean LIC According to the Presence or Absence of Retrospective Hepatic Events Hepatic event in past 12 months = yes (n=7)	17.51 mg Fe/g Standard Deviation 15.292	—	—	—	—
Mean LIC According to the Presence or Absence of Retrospective Hepatic Events Hepatic event in past 12 months = no (n=221)	10.08 mg Fe/g Standard Deviation 10.950	—	—	—	—

SECONDARY outcome

Timeframe: 1 month

Population: Participants with BMS values were analyzed.

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.

Outcome measures

Outcome measures
Measure	Magnetic Resonance Imaging (MRI) n=233 Participants All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload.	Thalassemia Major Subset of overall participants with thalassemia major	Melodysplastic Syndrome (MDS) Subset of overall participants with MDS	Non-transfusion-dependent Anaemia (NTDT) Subset of overall participants with NTDT	Other Anaemias Subset of overall participants with other types of anaemia
Mean Blood Magnetic Susceptibility (BMS)	-6.18 emu/g wet wt/Oe Standard Deviation 0.147	—	—	—	—

SECONDARY outcome

Timeframe: 12 months - retrospective

Population: Participants with a erythrocyte transfusion history were included in the analysis.

Transfusion requirement in participants with acquired anaemias with history of receiving chelation therapy was assessed.

Outcome measures

Outcome measures
Measure	Magnetic Resonance Imaging (MRI) n=241 Participants All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload.	Thalassemia Major n=81 Participants Subset of overall participants with thalassemia major	Melodysplastic Syndrome (MDS) n=73 Participants Subset of overall participants with MDS	Non-transfusion-dependent Anaemia (NTDT) n=19 Participants Subset of overall participants with NTDT	Other Anaemias n=68 Participants Subset of overall participants with other types of anaemia
Percentage of Participants Transfused With Erythrocytes	95.0 Percentage of participants	100.0 Percentage of participants	100.0 Percentage of participants	36.8 Percentage of participants	100.0 Percentage of participants

SECONDARY outcome

Timeframe: 12 months - retrospective

Population: Participants with data on time since their most recent transfusion were included in the analysis.

Transfusion requirement in participants with acquired anaemias with history of receiving chelation therapy was assessed.

Outcome measures

Outcome measures
Measure	Magnetic Resonance Imaging (MRI) n=241 Participants All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload.	Thalassemia Major n=81 Participants Subset of overall participants with thalassemia major	Melodysplastic Syndrome (MDS) n=68 Participants Subset of overall participants with MDS	Non-transfusion-dependent Anaemia (NTDT) n=19 Participants Subset of overall participants with NTDT	Other Anaemias n=65 Participants Subset of overall participants with other types of anaemia
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 < 7 days	43.1 percentage of participants	72.8 percentage of participants	31.0 percentage of participants	14.3 percentage of participants	22.7 percentage of participants
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 7 - < 14 days	12.9 percentage of participants	2.5 percentage of participants	28.2 percentage of participants	14.3 percentage of participants	9.1 percentage of participants
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 14 - < 30 days	20.0 percentage of participants	22.2 percentage of participants	14.1 percentage of participants	0.0 percentage of participants	25.8 percentage of participants
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 30 - < 60 days	5.8 percentage of participants	2.5 percentage of participants	9.9 percentage of participants	14.3 percentage of participants	4.5 percentage of participants
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 >= 60 days	18.2 percentage of participants	0.0 percentage of participants	16.9 percentage of participants	57.1 percentage of participants	37.9 percentage of participants

SECONDARY outcome

Timeframe: 12 months - retrospective

Population: Participants with 'number of units transfused' data were included in the analysis.

Transfusion requirement in participants with acquired anaemias with history of receiving chelation therapy was assessed.

Outcome measures

Outcome measures
Measure	Magnetic Resonance Imaging (MRI) n=228 Participants All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload.	Thalassemia Major n=81 Participants Subset of overall participants with thalassemia major	Melodysplastic Syndrome (MDS) n=72 Participants Subset of overall participants with MDS	Non-transfusion-dependent Anaemia (NTDT) n=7 Participants Subset of overall participants with NTDT	Other Anaemias n=68 Participants Subset of overall participants with other types of anaemia
Mean Number of Erythrocyte Units Transfused in Last 12 Months	33.3 number of units transfused Standard Deviation 21.0	41.4 number of units transfused Standard Deviation 9.5	34.7 number of units transfused Standard Deviation 25.6	8.4 number of units transfused Standard Deviation 12.2	24.8 number of units transfused Standard Deviation 21.5

SECONDARY outcome

Timeframe: 1 month

Population: Only participants with data for each subscale were included in the analysis for that subscale.

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.

Outcome measures

Outcome measures
Measure	Magnetic Resonance Imaging (MRI) n=243 Participants All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload.	Thalassemia Major n=81 Participants Subset of overall participants with thalassemia major	Melodysplastic Syndrome (MDS) n=74 Participants Subset of overall participants with MDS	Non-transfusion-dependent Anaemia (NTDT) n=20 Participants Subset of overall participants with NTDT	Other Anaemias n=68 Participants Subset of overall participants with other types of anaemia
Mean Quality of Life (QOL) Scores Physical functioning	43.10 units on a scale Standard Deviation 11.471	49.79 units on a scale Standard Deviation 9.144	35.67 units on a scale Standard Deviation 9.791	49.37 units on a scale Standard Deviation 7.576	41.56 units on a scale Standard Deviation 11.139
Mean Quality of Life (QOL) Scores Role physical	42.54 units on a scale Standard Deviation 10.895	49.51 units on a scale Standard Deviation 8.836	36.71 units on a scale Standard Deviation 9.462	46.46 units on a scale Standard Deviation 8.717	39.44 units on a scale Standard Deviation 10.229
Mean Quality of Life (QOL) Scores Bodily pain	48.41 units on a scale Standard Deviation 10.969	50.48 units on a scale Standard Deviation 11.084	45.52 units on a scale Standard Deviation 10.750	54.66 units on a scale Standard Deviation 7.773	47.60 units on a scale Standard Deviation 10.815
Mean Quality of Life (QOL) Scores General health	41.65 units on a scale Standard Deviation 9.909	44.82 units on a scale Standard Deviation 9.365	39.48 units on a scale Standard Deviation 9.595	43.23 units on a scale Standard Deviation 8.893	39.80 units on a scale Standard Deviation 10.239
Mean Quality of Life (QOL) Scores Vitality	45.59 units on a scale Standard Deviation 10.267	50.18 units on a scale Standard Deviation 9.277	42.41 units on a scale Standard Deviation 9.190	48.95 units on a scale Standard Deviation 8.424	42.67 units on a scale Standard Deviation 10.757
Mean Quality of Life (QOL) Scores Social functioning	44.99 units on a scale Standard Deviation 11.075	48.98 units on a scale Standard Deviation 9.869	42.37 units on a scale Standard Deviation 10.486	46.43 units on a scale Standard Deviation 9.905	42.67 units on a scale Standard Deviation 12.043
Mean Quality of Life (QOL) Scores Role emotional	43.83 units on a scale Standard Deviation 12.977	48.99 units on a scale Standard Deviation 11.236	40.11 units on a scale Standard Deviation 13.101	47.03 units on a scale Standard Deviation 10.552	40.89 units on a scale Standard Deviation 13.320
Mean Quality of Life (QOL) Scores Mental health	47.84 units on a scale Standard Deviation 11.149	50.09 units on a scale Standard Deviation 11.240	46.69 units on a scale Standard Deviation 9.495	48.74 units on a scale Standard Deviation 9.846	46.12 units on a scale Standard Deviation 12.632
Mean Quality of Life (QOL) Scores Physical component summary	43.48 units on a scale Standard Deviation 9.808	48.75 units on a scale Standard Deviation 7.809	37.55 units on a scale Standard Deviation 8.748	50.34 units on a scale Standard Deviation 6.392	41.93 units on a scale Standard Deviation 9.524
Mean Quality of Life (QOL) Scores Mental component summary	46.76 units on a scale Standard Deviation 11.622	49.58 units on a scale Standard Deviation 10.354	45.91 units on a scale Standard Deviation 10.349	47.47 units on a scale Standard Deviation 10.832	44.08 units on a scale Standard Deviation 13.822

SECONDARY outcome

Timeframe: 1 month

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Magnetic Resonance Imaging (MRI) n=141 Participants All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload.	Thalassemia Major n=78 Participants Subset of overall participants with thalassemia major	Melodysplastic Syndrome (MDS) n=34 Participants Subset of overall participants with MDS	Non-transfusion-dependent Anaemia (NTDT) n=4 Participants Subset of overall participants with NTDT	Other Anaemias n=25 Participants Subset of overall participants with other types of anaemia
Percentage of Participants With Low Medium or High Adherence to Iron Chelator Therapy Low	27.7 Percentage of participants	32.1 Percentage of participants	11.8 Percentage of participants	75.0 Percentage of participants	28.0 Percentage of participants
Percentage of Participants With Low Medium or High Adherence to Iron Chelator Therapy Medium	61.7 Percentage of participants	57.7 Percentage of participants	73.5 Percentage of participants	25.0 Percentage of participants	64.0 Percentage of participants
Percentage of Participants With Low Medium or High Adherence to Iron Chelator Therapy High	10.6 Percentage of participants	10.3 Percentage of participants	14.7 Percentage of participants	0.0 Percentage of participants	8.0 Percentage of participants

SECONDARY outcome

Timeframe: 2 months

Population: Participants, for whom treatment decision questionnaire results were provided and for whom MRI results were available, were included in the analysis.

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?".

Outcome measures

Outcome measures
Measure	Magnetic Resonance Imaging (MRI) n=229 Participants All participants were subjected to a non-invasive hepatic and cardiac MRI within 60 days of enrollment to measure iron overload.	Thalassemia Major Subset of overall participants with thalassemia major	Melodysplastic Syndrome (MDS) Subset of overall participants with MDS	Non-transfusion-dependent Anaemia (NTDT) Subset of overall participants with NTDT	Other Anaemias Subset of overall participants with other types of anaemia
Investigator Treatment Decisions Based on MRI Results Answer = yes	42.4 Percentage of participants	—	—	—	—
Investigator Treatment Decisions Based on MRI Results Answer = no	57.6 Percentage of participants	—	—	—	—

Adverse Events

Thalassaemia Major

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Myelodysplastic Syndrome (MDS)

Serious events: 8 serious events

Other events: 9 other events

Deaths: 0 deaths

Other Anaemia

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Non-transfusion-dependent Anaemia (NTDT)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Thalassaemia Major n=81 participants at risk Subset of overall participants with thalassemia major	Myelodysplastic Syndrome (MDS) n=74 participants at risk Subset of overall participants with MDS	Other Anaemia n=68 participants at risk Subset of overall participants with other types of anaemias	Non-transfusion-dependent Anaemia (NTDT) n=20 participants at risk Subset of overall participants with NTDT
Blood and lymphatic system disorders Anaemia	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/81	1.4% 1/74	2.9% 2/68	0.00% 0/20
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Cardiac disorders Angina pectoris	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Eye disorders Eye swelling	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Gastrointestinal disorders Diarrhoea	0.00% 0/81	2.7% 2/74	1.5% 1/68	0.00% 0/20
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
General disorders Malaise	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
General disorders Medical device site erosion	1.2% 1/81	0.00% 0/74	0.00% 0/68	0.00% 0/20
General disorders Medical device site pain	1.2% 1/81	0.00% 0/74	0.00% 0/68	0.00% 0/20
General disorders Medical device site swelling	1.2% 1/81	0.00% 0/74	0.00% 0/68	0.00% 0/20
General disorders Pyrexia	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Hepatobiliary disorders Cholecystitis acute	1.2% 1/81	0.00% 0/74	0.00% 0/68	0.00% 0/20
Infections and infestations Infection	1.2% 1/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Infections and infestations Klebsiella infection	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Infections and infestations Nasopharyngitis	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Infections and infestations Pneumonia	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Injury, poisoning and procedural complications Fall	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Investigations C-reactive protein increased	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Investigations Electrocardiogram QT prolonged	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Investigations Platelet count decreased	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Psychiatric disorders Anxiety	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20

Other adverse events

Other adverse events
Measure	Thalassaemia Major n=81 participants at risk Subset of overall participants with thalassemia major	Myelodysplastic Syndrome (MDS) n=74 participants at risk Subset of overall participants with MDS	Other Anaemia n=68 participants at risk Subset of overall participants with other types of anaemias	Non-transfusion-dependent Anaemia (NTDT) n=20 participants at risk Subset of overall participants with NTDT
Vascular disorders Hypotension	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Blood and lymphatic system disorders Anaemia	0.00% 0/81	1.4% 1/74	1.5% 1/68	0.00% 0/20
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Cardiac disorders Palpitations	0.00% 0/81	2.7% 2/74	0.00% 0/68	0.00% 0/20
Ear and labyrinth disorders Hypoacusis	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Eye disorders Dry eye	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Gastrointestinal disorders Abdominal pain	0.00% 0/81	4.1% 3/74	1.5% 1/68	0.00% 0/20
Gastrointestinal disorders Abdominal pain upper	1.2% 1/81	0.00% 0/74	0.00% 0/68	0.00% 0/20
Gastrointestinal disorders Constipation	0.00% 0/81	1.4% 1/74	1.5% 1/68	0.00% 0/20
Gastrointestinal disorders Diarrhoea	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Gastrointestinal disorders Nausea	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Gastrointestinal disorders Proctalgia	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
General disorders Asthenia	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
General disorders Chest pain	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
General disorders Fatigue	0.00% 0/81	2.7% 2/74	1.5% 1/68	0.00% 0/20
General disorders Influenza like illness	1.2% 1/81	0.00% 0/74	0.00% 0/68	0.00% 0/20
General disorders Injection site reaction	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
General disorders Oedema	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
General disorders Oedema peripheral	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
General disorders Pain	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
General disorders Pyrexia	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Infections and infestations Lower respiratory tract infection	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Infections and infestations Pneumonia	1.2% 1/81	0.00% 0/74	0.00% 0/68	0.00% 0/20
Infections and infestations Respiratory tract infection	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Infections and infestations Tonsillitis	1.2% 1/81	0.00% 0/74	0.00% 0/68	0.00% 0/20
Infections and infestations Upper respiratory tract infection	2.5% 2/81	0.00% 0/74	0.00% 0/68	0.00% 0/20
Infections and infestations Urinary tract infection	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Infections and infestations Viral infection	1.2% 1/81	0.00% 0/74	0.00% 0/68	0.00% 0/20
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Investigations Heart rate increased	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Metabolism and nutrition disorders Decreased appetite	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Metabolism and nutrition disorders Dehydration	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Metabolism and nutrition disorders Gout	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Nervous system disorders Headache	0.00% 0/81	2.7% 2/74	0.00% 0/68	0.00% 0/20
Nervous system disorders Sinus headache	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Psychiatric disorders Insomnia	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Psychiatric disorders Sleep disorder	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Renal and urinary disorders Haematuria	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/81	1.4% 1/74	0.00% 0/68	0.00% 0/20
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/81	0.00% 0/74	1.5% 1/68	0.00% 0/20

Additional Information

Study Director

Novartis

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER