T2* in Transfusion Dependant Anemia, MI, LVF, Normal Patients

• ClinicalTrials.gov Identifier: NCT00520559
• Recruitment Status: Completed
• First Posted: August 24, 2007
• Last Update Posted: April 16, 2019
• Sponsor: Imperial College London
• Information provided by: Imperial College London

Tracking Information

• First Submitted Date: August 23, 2007
• First Posted Date: August 24, 2007
• Last Update Posted Date: April 16, 2019
• Study Start Date: January 2007
• Primary Completion Date: Not Provided
• Current Primary Outcome Measures: Not Provided
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: T2* in Transfusion Dependant Anemia, MI, LVF, Normal Patients
• Official Title: Incidence of Cardiac Complications in Patients With Cardiac Siderosis During 1 Year Follow-up and the Normal T2* Ranges in LVF, MI and Normal Population.
• Brief Summary: The purpose of this study is to provide accurate prognostic data linking cardiac complications to myocardial T2* values (A measure of iron levels in the heart using MRI)in patients predisposed to heart iron overload.

Detailed Description

Key Definitions Myocardial siderosis - Iron deposition that occurs in the heart, usually in relation to recurrent blood transfusions and red cell breakdown.

Thalassaemia - A hereditary form of anaemia leading to recurrent blood transfusions and iron overload.

Cardiomyopathy - Disease of the heart leading to heart failure. In the case of cardiac siderosis it is entirely reversible.

Chelation - Drug used to remove iron from the heart T2* CMR - Cardiac Magnetic Resonance Imaging. A specialised scan that uses a large magnet to image the heart. As iron has magnetic properties we can use this scan to determine the amount of iron within the heart. T2* is a value that relates to the level of iron loading in the heart. A T2* of less than 10 relates to severe heart iron loading, a T2* of 10-20 relates to mild/moderate heart iron loading and a T2* of greater than 20 relates to no significant iron loading in the heart.

Heart failure - Disease in which the myocardium (heart muscle) weakens and can not pump blood efficiently. Fluid accumulates in the lungs, hands, ankles, or other parts of the body. The mortality from heart failure is very high.

Heterozygotes - An individual with one normal and one abnormal thalassaemia gene. They are carriers of the thalassaemia gene with milder clinical manifestations.

Homozygotes - An individual who has inherited both abnormal thalassaemia genes producing a more severe form of the disease.

Question Response Although a rare disease in the UK, thalassaemia is the commonest genetic disorder worldwide, with approximately 94 million heterozygotes for beta thalassaemia and 60,000 homozygotes born each year.

In the United Kingdom, despite relatively easy access to healthcare, approximately 50% of patients with thalassaemia major die before reaching the age of thirty five. Of those deaths, over 60% are a result of heart failure. The cardiomyopathy is reversible if chelation is commenced early but diagnosis is often delayed due to the late onset of symptoms and measurable LV dysfunction.

This study will provide strong evidence that a myocardial T2* <10ms represents a high risk of developing cardiac complications. Derived risk ratios will provide sound guidance as to when life saving chelation is required.

A database will be produced containing clinical data and T2* values on 665 thalassaemia patients from 1998-2006.

A diagnosis of heart failure will be made if the patient has had an ejection fraction of less than 55% (measured by CMR or echocardiography) and symptoms as per NHYA classification within 1 year of their CMR scan.

A diagnosis of arrhythmia was made if the patient had documented ECG evidence within 1 year of their CMR scan.

This information will be gathered retrospectively by access to outpatient clinic letters, hospital notes, CMR/ echo reports and clinical details recorded in a proforma at the time of the CMR scan. Some of the clinical data would be obtained from other hospitals.

Patient scans will only be used if between the dates of 1999-2005. As all other data is in respect to the year immediately post scan then no further data will be required on any patient post 2006.

Logistic regression will be used to determine whether T2* is predictive of cardiac complications in the 12 months after a patient's CMR scan. Since some patients will have more than 1 scan, a mixed model logistic regression will be used to take account of any within-patient correlation that may occur.

The data will be analysed by Dr Michael Roughton (Medical Statistician, Royal Brompton Hospital)

The results will be disseminated through peer review journals

• Study Type: Observational
• Study Design: Time Perspective: Retrospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Not Provided
• Study Population: Not Provided
• Condition: Thalassemia
• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided

Publications *

• Kirk P, Sheppard M, Carpenter JP, Anderson L, He T, St Pierre T, Galanello R, Catani G, Wood J, Fucharoen S, Porter JB, Walker JM, Forni GL, Pennell DJ. Post-mortem study of the association between cardiac iron and fibrosis in transfusion dependent anaemia. J Cardiovasc Magn Reson. 2017 Mar 27;19(1):36. doi: 10.1186/s12968-017-0349-3.
• Kirk P, He T, Anderson LJ, Roughton M, Tanner MA, Lam WW, Au WY, Chu WC, Chan G, Galanello R, Matta G, Fogel M, Cohen AR, Tan RS, Chen K, Ng I, Lai A, Fucharoen S, Laothamata J, Chuncharunee S, Jongjirasiri S, Firmin DN, Smith GC, Pennell DJ. International reproducibility of single breathhold T2* MR for cardiac and liver iron assessment among five thalassemia centers. J Magn Reson Imaging. 2010 Aug;32(2):315-9. doi: 10.1002/jmri.22245.
• Kirk P, Roughton M, Porter JB, Walker JM, Tanner MA, Patel J, Wu D, Taylor J, Westwood MA, Anderson LJ, Pennell DJ. Cardiac T2* magnetic resonance for prediction of cardiac complications in thalassemia major. Circulation. 2009 Nov 17;120(20):1961-8. doi: 10.1161/CIRCULATIONAHA.109.874487. Epub 2009 Oct 2.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 23, 2007): 665
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: August 2007
• Primary Completion Date: Not Provided

Eligibility Criteria

Inclusion Criteria:

• Thalassaemia Major
• Patient must have had a cardiac MRI scan between 1999 and 2006

Exclusion Criteria:

• Other structural heart disease such as valvular abnormalities, MI, congenital heart disease

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT00520559
• Other Study ID Numbers: 07/MRE04/32
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Not Provided
• Original Responsible Party: Same as current
• Current Study Sponsor: Imperial College London
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Dudley Pennell, MA, MD; Imperial College London

• PRS Account: Imperial College London
• Verification Date: April 2019