Cardiac T2* in Beta-thalassemia Patients on Deferasirox Treatment

• ClinicalTrials.gov Identifier: NCT00447694
• Recruitment Status: Completed
• First Posted: March 15, 2007
• Results First Posted: June 7, 2021
• Last Update Posted: June 14, 2021
• Sponsor: Novartis
• Information provided by (Responsible Party): Novartis

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Beta-thalassemia; Iron Overload
• Intervention: Drug: Deferasirox
• Enrollment: 30

Participant Flow

Recruitment Details	The study was conducted at 4 centers in the United States
Pre-assignment Details	A total number of participants planned for this study was 30. The total number of 28 participants enrolled in the study, of these 22 completed the study and 6 discontinued the study.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received Deferasirox 30 milligrams per kilogram per day (mg/kg/day) orally once daily (OD), 30 minutes before breakfast, preferably around the same time every morning if possible. Deferasirox tablets were dropped into water or orange juice, or apple juice and stirred until completely dispersed. For doses less than 1 gram (g), tablets were dissolved in at least 100 milliliter (mL) of liquid; for doses of 1 to 3 g, tablets were dissolved in at least 200 mL. After tablets were fully disintegrated, the liquid was promptly consumed.
Period Title: Overall Study
Started	28
Completed	22
Not Completed	6
Reason Not Completed
Adverse Event	2
Abnormal laboratory value	1
Abnormal test procedure result	1
Withdrawal by Subject	2

Baseline Characteristics

Arm/Group Title		Deferasirox
Arm/Group Description		Participants received Deferasirox 30 mg/kg/day orally OD, 30 minutes before breakfast, preferably around the same time every morning if possible. Deferasirox tablets were dropped into water or orange juice, or apple juice and stirred until completely dispersed. For doses less than 1 g, tablets were dissolved in at least 100 mL of liquid; for doses of 1 to 3 g, tablets were dissolved in at least 200 mL. After tablets were fully disintegrated, the liquid was promptly consumed.
Overall Number of Baseline Participants		28
Baseline Analysis Population Description		The analysis was performed in Intent-to-treat (ITT) population, defined as all enrolled participants who received at least 1 dose of study drug and had at least 1 post-baseline assessment.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	28 participants
		22.6 (8.67)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	28 participants
	Female	20 71.4%
	Male	8 28.6%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	28 participants
Caucasian		9
Black		0
Oriental		7
Other		12

Outcome Measures

1. Primary Outcome

Title	Magnetic Resonance Imaging (MRI) T2* and Absolute Change From Baseline in MRI T2*
Description	Cardiac T2* was measured in the short axis plane at the widest point of a 4-chamber localizer using custom breath-hold R2* gradient echo sequences modeled after techniques used by Anderson et al (2001) and Westwood et al (2003).
Time Frame	From Baseline to 25, 49, 77 Week

Outcome Measure Data

Analysis Population Description

The analysis was performed in Completer population (CP) consists of those participants who had a Week 77 MRI.

Arm/Group Title		Deferasirox
Arm/Group Description:		Participants received Deferasirox 30 mg/kg/day orally OD, 30 minutes before breakfast, preferably around the same time every morning if possible. Deferasirox tablets were dropped into water or orange juice, or apple juice and stirred until completely dispersed. For doses less than 1 g, tablets were dissolved in at least 100 mL of liquid; for doses of 1 to 3 g, tablets were dissolved in at least 200 mL. After tablets were fully disintegrated, the liquid was promptly consumed.
Overall Number of Participants Analyzed		22
Mean (Standard Deviation); Unit of Measure: milliseconds (msec)
Baseline	Number Analyzed	22 participants
		9.92 (3.922)
Week 25	Number Analyzed	21 participants
		11.73 (6.091)
Week 25 Absolute Change from Baseline	Number Analyzed	21 participants
		1.77 (3.203)
Week 49	Number Analyzed	22 participants
		11.93 (6.489)
Week 49 Absolute Change from Baseline	Number Analyzed	22 participants
		2.01 (3.792)
Week 77	Number Analyzed	22 participants
		12.10 (6.461)
Week 77 Absolute Change from Baseline	Number Analyzed	22 participants
		2.18 (3.927)

2. Secondary Outcome

Title	Change From Baseline in Liver Iron Concentration (LIC) Was Measured by MRI R2 From Absolute Change From Baseline to 101 Weeks
Description	MRI evaluation of liver iron concentration has been validated by liver biopsy (St Pierre et al 2005). Studies comparing T2* values of liver iron concentration (LIC) with LIC as assessed by biopsy have confirmed that T2* values reflect liver iron content (Wood et al 2003b). Direct tissue-validation of cardiac T2* measurements in humans has not been performed because endomyocardial biopsy is a dangerous and unreliable indicator of cardiac iron overload (Olson et al 1989, Fitchett et al 1980). However, it has been shown that cardiac T2* accurately reflects cardiac iron in a gerbil iron cardiomyopathy model (Wood et al 2004b). T2* measurements have shown excellent inter-scanner and inter-exam reproducibility, making them suitable for longitudinal monitoring (Westwood et al 2003a, Westwood et al 2003b).
Time Frame	From Baseline to 25, 49, 77 Week

Outcome Measure Data

Analysis Population Description

The analysis was performed in Completer population consists of those participants who had a Week 77 MRI.

Arm/Group Title		Deferasirox
Arm/Group Description:		Participants received Deferasirox 30 mg/kg/day orally OD, 30 minutes before breakfast, preferably around the same time every morning if possible. Deferasirox tablets were dropped into water or orange juice, or apple juice and stirred until completely dispersed. For doses less than 1 g, tablets were dissolved in at least 100 mL of liquid; for doses of 1 to 3 g, tablets were dissolved in at least 200 mL. After tablets were fully disintegrated, the liquid was promptly consumed.
Overall Number of Participants Analyzed		22
Mean (Standard Deviation); Unit of Measure: mg Fe/g dw liver
Baseline	Number Analyzed	22 participants
		19.85 (3.309)
Week 25	Number Analyzed	21 participants
		17.23 (15.393)
Week 25 Absolute Change from Baseline	Number Analyzed	21 participants
		-2.89 (4.169)
Week 49	Number Analyzed	22 participants
		17.0 (17.548)
Week 49 Absolute Change from Baseline	Number Analyzed	22 participants
		-2.85 (4.883)
Week 77	Number Analyzed	22 participants
		16.62 (20.114)
Week 77 Absolute Change from Baseline	Number Analyzed	22 participants
		-3.23 (7.708)

3. Secondary Outcome

Title	Left Ventricular Ejection Fraction (LVEF) and Change in Left Ventricular Ejection Fraction From Baseline to 101 Weeks
Description	Magnetic resonance imaging (MRI)-measured cardiac T2* and cardiac function reflected by left and right ventricle ejection fraction. A standardized MRI protocol for T2* acquisition technique will be used in the centers. Images will be reviewed centrally by an expert MRI reader.
Time Frame	From Baseline to 25, 49, 77 Week

Outcome Measure Data

Analysis Population Description

The analysis was performed in Completer population consisting of those participants who had a Week 77 MRI.

Arm/Group Title		Deferasirox
Arm/Group Description:		Participants received Deferasirox 30 mg/kg/day orally OD, 30 minutes before breakfast, preferably around the same time every morning if possible. Deferasirox tablets were dropped into water or orange juice, or apple juice and stirred until completely dispersed. For doses less than 1 g, tablets were dissolved in at least 100 mL of liquid; for doses of 1 to 3 g, tablets were dissolved in at least 200 mL. After tablets were fully disintegrated, the liquid was promptly consumed.
Overall Number of Participants Analyzed		22
Mean (Standard Deviation); Unit of Measure: percentage of participants
Baseline	Number Analyzed	21 participants
		64.01 (6.751)
Week 25	Number Analyzed	21 participants
		62.17 (6.352)
Week 25 Absolute change from baseline	Number Analyzed	21 participants
		-1.84 (7.306)
Week 49	Number Analyzed	22 participants
		61.61 (13.726)
Week 49 Absolute change from baseline	Number Analyzed	21 participants
		-2.68 (14.546)
Week 77	Number Analyzed	22 participants
		63.84 (6.112)
Week 77 Absolute change from baseline	Number Analyzed	21 participants
		0.11 (7.299)

4. Secondary Outcome

Title	Serum Ferritin and Changes From Baseline in Serum Ferritin During Study
Description	Serum ferritin will be assessed at each study visit. Analysis was performed in Completer population consists of those participants who had a Week 77 MRI.
Time Frame	From Baseline to 25, 49, 77 Week

Outcome Measure Data

Analysis Population Description

The analysis was performed in Completer population consists of those participants who had a Week 77 MRI.

Arm/Group Title		Deferasirox
Arm/Group Description:		Participants received Deferasirox 30 mg/kg/day orally OD, 30 minutes before breakfast, preferably around the same time every morning if possible. Deferasirox tablets were dropped into water or orange juice, or apple juice and stirred until completely dispersed. For doses less than 1 g, tablets were dissolved in at least 100 mL of liquid; for doses of 1 to 3 g, tablets were dissolved in at least 200 mL. After tablets were fully disintegrated, the liquid was promptly consumed.
Overall Number of Participants Analyzed		22
Mean (Standard Deviation); Unit of Measure: μg/L
Baseline	Number Analyzed	22 participants
		4343.75 (3486.525)
Week 25	Number Analyzed	22 participants
		4280.77 (5261.563)
Week 25 Absolute change from baseline	Number Analyzed	22 participants
		-62.98 (2294.635)
Week 49	Number Analyzed	21 participants
		3759.29 (3966.107)
Week 49 Absolute change from baseline	Number Analyzed	21 participants
		-593.36 (1534.040)
Week 77	Number Analyzed	21 participants
		3179.81 (3439.357)
Week 77 Absolute change from baseline	Number Analyzed	21 participants
		-882.74 (1368.202)

Adverse Events

Time Frame	Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit (LPLV) up to week 77.
Adverse Event Reporting Description	The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Arm/Group Title	All Patients
Arm/Group Description	Participants received Deferasirox 30 mg/kg/day orally OD, 30 minutes before breakfast, preferably around the same time every morning if possible. Deferasirox tablets were dropped into water or orange juice, or apple juice and stirred until completely dispersed. For doses less than 1 g, tablets were dissolved in at least 100 mL of liquid; for doses of 1 to 3 g, tablets were dissolved in at least 200 mL. After tablets were fully disintegrated, the liquid was promptly consumed.
All-Cause Mortality
	All Patients
	Affected / at Risk (%)
Total	0/27 (0.00%)
Serious Adverse Events
	All Patients
	Affected / at Risk (%)
Total	8/27 (29.63%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation † 1	1/27 (3.70%)
Thrombocytopenia † 1	1/27 (3.70%)
Cardiac disorders
Arrhythmia † 1	1/27 (3.70%)
Cardiac failure † 1	1/27 (3.70%)
Tachycardia † 1	1/27 (3.70%)
Congenital, familial and genetic disorders
Fanconi syndrome † 1	1/27 (3.70%)
Gastrointestinal disorders
Abdominal compartment syndrome † 1	1/27 (3.70%)
Abdominal pain † 1	4/27 (14.81%)
Ascites † 1	1/27 (3.70%)
Colitis † 1	1/27 (3.70%)
Gastrointestinal oedema † 1	1/27 (3.70%)
Nausea † 1	1/27 (3.70%)
Pancreatitis † 1	1/27 (3.70%)
Vomiting † 1	3/27 (11.11%)
General disorders
Multi-organ failure † 1	1/27 (3.70%)
Pyrexia † 1	5/27 (18.52%)
Hepatobiliary disorders
Hepatic failure † 1	1/27 (3.70%)
Hepatic steatosis † 1	1/27 (3.70%)
Hepatitis † 1	1/27 (3.70%)
Infections and infestations
Aspergillosis † 1	1/27 (3.70%)
Bacterial infection † 1	1/27 (3.70%)
Bronchitis viral † 1	1/27 (3.70%)
Herpes simplex † 1	1/27 (3.70%)
Pneumonia † 1	1/27 (3.70%)
Sepsis † 1	1/27 (3.70%)
Septic shock † 1	1/27 (3.70%)
Urinary tract infection † 1	1/27 (3.70%)
Urinary tract infection fungal † 1	1/27 (3.70%)
Injury, poisoning and procedural complications
Fibula fracture † 1	1/27 (3.70%)
Splenic rupture † 1	1/27 (3.70%)
Tibia fracture † 1	1/27 (3.70%)
Investigations
Blood creatinine increased † 1	1/27 (3.70%)
Blood phosphorus decreased † 1	1/27 (3.70%)
Ejection fraction decreased † 1	1/27 (3.70%)
Urine analysis abnormal † 1	1/27 (3.70%)
Metabolism and nutrition disorders
Acidosis † 1	1/27 (3.70%)
Acidosis hyperchloraemic † 1	1/27 (3.70%)
Anorexia † 1	1/27 (3.70%)
Dehydration † 1	2/27 (7.41%)
Hyperglycaemia † 1	1/27 (3.70%)
Musculoskeletal and connective tissue disorders
Back pain † 1	1/27 (3.70%)
Nervous system disorders
Depressed level of consciousness † 1	1/27 (3.70%)
Unresponsive to stimuli † 1	1/27 (3.70%)
Psychiatric disorders
Mental status changes † 1	1/27 (3.70%)
Psychotic disorder † 1	1/27 (3.70%)
Renal and urinary disorders
Azotaemia † 1	1/27 (3.70%)
Polyuria † 1	1/27 (3.70%)
Renal failure † 1	1/27 (3.70%)
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain † 1	1/27 (3.70%)
Pulmonary oedema † 1	1/27 (3.70%)
Respiratory failure † 1	1/27 (3.70%)
Vascular disorders
Hypoperfusion † 1	1/27 (3.70%)
Hypotension † 1	2/27 (7.41%)
Shock † 1	1/27 (3.70%)
1 Term from vocabulary, MedDRA (12.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	All Patients
	Affected / at Risk (%)
Total	27/27 (100.00%)
Cardiac disorders
Left atrial dilatation † 1	1/27 (3.70%)
Left ventricular hypertrophy † 1	2/27 (7.41%)
Sinus bradycardia † 1	1/27 (3.70%)
Sinus tachycardia † 1	1/27 (3.70%)
Tachycardia † 1	2/27 (7.41%)
Ear and labyrinth disorders
Vertigo † 1	1/27 (3.70%)
Eye disorders
Conjunctivitis † 1	1/27 (3.70%)
Conjunctivitis allergic † 1	1/27 (3.70%)
Dry eye † 1	1/27 (3.70%)
Eye irritation † 1	1/27 (3.70%)
Gastrointestinal disorders
Abdominal pain † 1	7/27 (25.93%)
Abdominal pain lower † 1	1/27 (3.70%)
Constipation † 1	2/27 (7.41%)
Diarrhoea † 1	12/27 (44.44%)
Dyspepsia † 1	1/27 (3.70%)
Gastritis † 1	1/27 (3.70%)
Nausea † 1	16/27 (59.26%)
Vomiting † 1	6/27 (22.22%)
General disorders
Chest discomfort † 1	3/27 (11.11%)
Chills † 1	2/27 (7.41%)
Fatigue † 1	9/27 (33.33%)
Non-cardiac chest pain † 1	1/27 (3.70%)
Oedema † 1	1/27 (3.70%)
Oedema peripheral † 1	1/27 (3.70%)
Pain † 1	2/27 (7.41%)
Pyrexia † 1	10/27 (37.04%)
Hepatobiliary disorders
Cholelithiasis † 1	1/27 (3.70%)
Immune system disorders
House dust allergy † 1	1/27 (3.70%)
Infections and infestations
Candidiasis † 1	1/27 (3.70%)
Ear infection † 1	1/27 (3.70%)
Folliculitis † 1	1/27 (3.70%)
Fungal infection † 1	1/27 (3.70%)
Hordeolum † 1	1/27 (3.70%)
Nasopharyngitis † 1	11/27 (40.74%)
Oral herpes † 1	1/27 (3.70%)
Pharyngitis † 1	1/27 (3.70%)
Sinusitis † 1	3/27 (11.11%)
Upper respiratory tract infection † 1	4/27 (14.81%)
Urinary tract infection † 1	2/27 (7.41%)
Vulvovaginal mycotic infection † 1	2/27 (7.41%)
Injury, poisoning and procedural complications
Animal bite † 1	1/27 (3.70%)
Arthropod bite † 1	1/27 (3.70%)
Arthropod sting † 1	1/27 (3.70%)
Clavicle fracture † 1	1/27 (3.70%)
Contusion † 1	1/27 (3.70%)
Excoriation † 1	2/27 (7.41%)
Joint injury † 1	1/27 (3.70%)
Thoracic vertebral fracture † 1	1/27 (3.70%)
Wrist fracture † 1	1/27 (3.70%)
Investigations
Alanine aminotransferase increased † 1	2/27 (7.41%)
Aspartate aminotransferase increased † 1	2/27 (7.41%)
Blood 1,25-dihydroxycholecalciferol decreased † 1	1/27 (3.70%)
Blood creatinine increased † 1	2/27 (7.41%)
Ejection fraction decreased † 1	1/27 (3.70%)
Electrocardiogram ST-T change † 1	2/27 (7.41%)
Hepatic enzyme increased † 1	1/27 (3.70%)
Transaminases increased † 1	1/27 (3.70%)
Urine albumin/creatinine ratio abnormal † 1	1/27 (3.70%)
Urine albumin/creatinine ratio increased † 1	1/27 (3.70%)
Urine output decreased † 1	2/27 (7.41%)
Weight decreased † 1	1/27 (3.70%)
Metabolism and nutrition disorders
Alkalosis † 1	1/27 (3.70%)
Anorexia † 1	1/27 (3.70%)
Carnitine deficiency † 1	2/27 (7.41%)
Copper deficiency † 1	1/27 (3.70%)
Decreased appetite † 1	1/27 (3.70%)
Dehydration † 1	1/27 (3.70%)
Hyperglycaemia † 1	2/27 (7.41%)
Hyperkalaemia † 1	1/27 (3.70%)
Hypocalcaemia † 1	1/27 (3.70%)
Hypoglycaemia † 1	1/27 (3.70%)
Hypokalaemia † 1	1/27 (3.70%)
Selenium deficiency † 1	1/27 (3.70%)
Vitamin A deficiency † 1	1/27 (3.70%)
Vitamin B complex deficiency † 1	3/27 (11.11%)
Vitamin B1 deficiency † 1	1/27 (3.70%)
Vitamin B12 deficiency † 1	1/27 (3.70%)
Vitamin B6 deficiency † 1	1/27 (3.70%)
Vitamin C deficiency † 1	1/27 (3.70%)
Vitamin D deficiency † 1	5/27 (18.52%)
Vitamin E deficiency † 1	1/27 (3.70%)
Zinc deficiency † 1	2/27 (7.41%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	6/27 (22.22%)
Back pain † 1	3/27 (11.11%)
Bone pain † 1	1/27 (3.70%)
Extremity contracture † 1	1/27 (3.70%)
Flank pain † 1	1/27 (3.70%)
Joint range of motion decreased † 1	1/27 (3.70%)
Myalgia † 1	2/27 (7.41%)
Neck pain † 1	1/27 (3.70%)
Osteopenia † 1	1/27 (3.70%)
Pain in extremity † 1	3/27 (11.11%)
Nervous system disorders
Basal ganglion degeneration † 1	1/27 (3.70%)
Dizziness † 1	5/27 (18.52%)
Headache † 1	9/27 (33.33%)
Hypoaesthesia † 1	1/27 (3.70%)
Paraesthesia † 1	1/27 (3.70%)
Psychiatric disorders
Insomnia † 1	1/27 (3.70%)
Renal and urinary disorders
Chromaturia † 1	1/27 (3.70%)
Dysuria † 1	1/27 (3.70%)
Reproductive system and breast disorders
Dysmenorrhoea † 1	1/27 (3.70%)
Respiratory, thoracic and mediastinal disorders
Asthma † 1	1/27 (3.70%)
Cough † 1	10/27 (37.04%)
Dyspnoea † 1	1/27 (3.70%)
Nasal congestion † 1	4/27 (14.81%)
Pharyngolaryngeal pain † 1	3/27 (11.11%)
Postnasal drip † 1	1/27 (3.70%)
Respiratory tract congestion † 1	1/27 (3.70%)
Wheezing † 1	1/27 (3.70%)
Skin and subcutaneous tissue disorders
Dermatitis contact † 1	1/27 (3.70%)
Ingrown hair † 1	1/27 (3.70%)
Rash † 1	7/27 (25.93%)
Skin irritation † 1	1/27 (3.70%)
Urticaria † 1	3/27 (11.11%)
Surgical and medical procedures
Wisdom teeth removal † 1	1/27 (3.70%)
Vascular disorders
Hypertension † 1	1/27 (3.70%)
Hypotension † 1	2/27 (7.41%)
1 Term from vocabulary, MedDRA (12.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Study Director
• Organization: Novartis Pharmaceuticals
• Phone: 862-778-8300
• EMail: Novartis.email@novartis.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wood JC, Glynos T, Thompson A, Giardina P, Harmatz P, Kang BP, Paley C, Coates TD. Relationship between labile plasma iron, liver iron concentration and cardiac response in a deferasirox monotherapy trial. Haematologica. 2011 Jul;96(7):1055-8. doi: 10.3324/haematol.2010.032862. Epub 2011 Mar 10.

Wood JC, Kang BP, Thompson A, Giardina P, Harmatz P, Glynos T, Paley C, Coates TD. The effect of deferasirox on cardiac iron in thalassemia major: impact of total body iron stores. Blood. 2010 Jul 29;116(4):537-43. doi: 10.1182/blood-2009-11-250308. Epub 2010 Apr 26.

• Responsible Party: Novartis
• ClinicalTrials.gov Identifier: NCT00447694
• Other Study ID Numbers: CICL670AUS04
• First Submitted: March 13, 2007
• First Posted: March 15, 2007
• Results First Submitted: May 11, 2021
• Results First Posted: June 7, 2021
• Last Update Posted: June 14, 2021