Cardiac T2* in Beta-thalassemia Patients on Deferasirox Treatment

Iron Overload Clinical Trial

Official title:

An Open Label Trial Evaluating Cardiac T2* in Beta-thalassemia Patients on Deferasirox (ICL670) Treatment for 18 Months

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00447694
• Other study ID #: CICL670AUS04
• Status: Completed
• Phase: Phase 2
• Start date: February 2006
• Est. completion date: November 2009

Study information

• Verified date: June 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is to evaluate changes in cardiac iron as measured by MRI T2* in beta-thalassemia patients with deferasirox treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years and older

Eligibility

Inclusion Criteria:

• Male or female ß-thalassemia outpatients on chronic transfusion therapy (defined as > 8 transfusions per year)

• Lifetime minimum of 100 previous packed red blood cell transfusions

• Patients currently on chelation therapy will require a one day wash out prior to the first dose of study drug

• Age = 10 years

• Sexually active females of childbearing potential must have a negative serum or urine pregnancy test and use an effective method of contraception, or must have undergone clinically documented total hysterectomy.

Exclusion Criteria:

• Ejection Fraction < 56 % measured using steady-state free precession imaging by MRI

• Contraindication to MRI, including cardiac pacemaker, brain aneurysm clip, implanted neurostimulator, insulin pump, cochlear implant, metal slivers in the eyes, intrauterine device or any other MRI incompatible metal implants or intractable claustrophobia

• Abnormal laboratory values as defined by the protocol

• Clinical or laboratory evidence of active Hepatitis B or Hepatitis C

• History of HIV positive test result (ELISA or Western blot)

• Uncontrolled systemic hypertension

• Second or third degree A-V block

• Life-threatening arrhythmias, including sustained ventricular tachycardia and aborted sudden death, within the last year

• History of cardiac conditions or unstable cardiac disease not controlled by standard medical therapy

• History of clinically relevant ocular toxicity related to iron chelation

• Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent study treatment

• Pregnancy or breast feeding (documented negative pregnancy test required for study entry)

• Patients enrolled in an ongoing clinical trial of deferasirox (ICL670) cannot be withdrawn in order to participate in this study

• Treatment with systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days

• Other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug

• History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative

• Other inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Beta-thalassemia
• Iron Overload
• Thalassemia

Intervention

Drug:
• Deferasirox
Oral deferasirox 30mg/kg/day once per day for 77 weeks.

Locations

Country	Name	City	State
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Childrens Hospital of Los Angeles	Los Angeles	California
United States	Children's Hospital and Research Center at Oakland	Oakland	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Magnetic Resonance Imaging (MRI) T2* and Absolute Change From Baseline in MRI T2*	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).	From Baseline to 25, 49, 77 Week
Secondary	Change From Baseline in Liver Iron Concentration (LIC) Was Measured by MRI R2 From Absolute Change From Baseline to 101 Weeks	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).	From Baseline to 25, 49, 77 Week
Secondary	Left Ventricular Ejection Fraction (LVEF) and Change in Left Ventricular Ejection Fraction From Baseline to 101 Weeks	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.	From Baseline to 25, 49, 77 Week
Secondary	Serum Ferritin and Changes From Baseline in Serum Ferritin During Study	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.	From Baseline to 25, 49, 77 Week

External Links

•   Novartis Clinical Trial results website