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Efficacy Study in Removing Excess Iron From the Heart

Primary Purpose

Thalassemia Major, Hemosiderosis

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Ferriprox (deferiprone)
Desferal (deferoxamine)
Sponsored by
ApoPharma
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Thalassemia Major focused on measuring Iron Overload, Thalassemia, Haemosiderosis, Cardiac, Deferiprone, Chelation

Eligibility Criteria

18 Years - 36 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Diagnosis of thalassemia major as confirmed by laboratory and clinical criteria Participants who are well transfused-maintaining a mean pre-transfusion Hb (hemoglobin) no less than 9 g/dL. Between 18 and 36 years of age. Receiving ongoing chelation therapy with deferoxamine for at least the past five years. Those who have been exposed to deferiprone for ≤ 6 months but not within the last 2 years prior to commencement of this study will be considered eligible to participate. Abnormal heart MRI T2* greater than or equal to 8 ms and < 20 ms. If female, fertile, and is neither pregnant nor lactating, confirms she will use an effective method of contraception for the length of the trial and has a negative pregnancy test immediately prior to commencement of study drug OR has had a tubal ligation OR a hysterectomy OR is post menopausal (at least 1 year no menses prior to enrollment in the study) OR their only sexual partner has been sterilized (if male). If male and fertile, he confirms that he and/or his partner will use an effective method of contraception for the length of the trial. Provide a signed and witnessed written informed consent obtained prior to the first study intervention. Exclusion Criteria: Have anemia other than thalassemia. HIV antibody positive. Clinical evidence of cardiomyopathy as shown by LV Shortening Fraction < 30 % and/or CMR derived LV (left ventricular) Ejection Fraction < 56 %. Severe/significant arrhythmia, including those who have had atrial fibrillation (participants with occasional ectopic beats and normal echo can be included) or those requiring treatment. Previously discontinued therapy with deferiprone or deferoxamine because of an adverse drug reaction to either chelator. Have received deferiprone in the last five years. However those who have been exposed to deferiprone for ≤ 6 months but not within the last 2 years prior to commencement of this study will be considered eligible to participate. Evidence of abnormal liver function (liver enzymes > 3 times upper limit of normal - entry may be delayed until return to normal). Have disorders associated with neutropenia (ANC < 1.5 x 10^9/L) or thrombocytopenia (platelet count <50 x 10^9/L) in the twelve months prior to start of study medication, except for participants who have been treated with interferon and in whom the ANC has fully recovered. Participants with neutropenia or thrombocytopenia in the last year, which resolved with splenectomy, may be considered for this study. Those who refuse to participate in the screening procedures or who are unable to participate in screening procedures or who are unable to comply with requirements of the protocol. Receiving other investigational products. Those in the opinion of the Investigator, who represent poor medical, psychological or psychiatric risks for whom participation in an investigational trial would be unwise. Those who are pregnant, breastfeeding or planning to become pregnant during the study period. Metallic objects in his/her body, such as artificial joints, inner ear (cochlear) implants, brain aneurysm clips, pacemakers, and metallic foreign bodies in the eye or other body areas. History of malignancy. Participants with claustrophobia. History of alcohol or drug abuse. Participants who are, in the opinion of the Investigator, excessively obese.

Sites / Locations

  • 1st Department of Pediatrics, Athens University, Aghia Sophia Children's Hospital
  • Aghia Sophia Children's Hospital
  • Ospedale Regionale Microcitemie, Dipartimento di Scienze
  • Dipartimento di Scienze e Dell' Adolescenza, University of Turin

Outcomes

Primary Outcome Measures

To determine whether deferiprone exhibits superior efficacy in removing excess iron from the heart compared to that of deferoxamine, as reflected by MRI T2* assessments in the heart in participants treated with either chelator

Secondary Outcome Measures

To evaluate the relative efficacy of deferiprone with respect to that of deferoxamine as assessed by serum ferritin concentration and liver iron concentration (LIC)

Full Information

First Posted
March 15, 2005
Last Updated
January 4, 2016
Sponsor
ApoPharma
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1. Study Identification

Unique Protocol Identification Number
NCT00105495
Brief Title
Efficacy Study in Removing Excess Iron From the Heart
Official Title
Randomized Trial Comparing the Relative Efficacy of Deferiprone to That of Deferoxamine in Removing Excess Cardiac Iron in Thalassemia Major Patients
Study Type
Interventional

2. Study Status

Record Verification Date
October 2006
Overall Recruitment Status
Completed
Study Start Date
December 2002 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
October 2004 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
ApoPharma

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to determine whether deferiprone has superior efficacy in removing excess iron from the heart when compared with deferoxamine.
Detailed Description
This study is a multi-center, randomized, open-label, controlled clinical trial. The study population is participants with thalassemia major who are receiving regular chelation therapy with deferoxamine. A total of sixty (60) participants will be enrolled among the investigative sites. The primary objective of this study is to determine whether deferiprone exhibits superior efficacy in removing excess iron from the heart compared to that of the standard therapy, deferoxamine. The secondary objective is to evaluate the relative efficacy of deferiprone with respect to that of deferoxamine as assessed by serum ferritin concentration and liver iron concentration. The primary efficacy measure in this study will be the participants' cardiac iron status, as determined by heart MRI T2* assessments. The secondary efficacy measure will be by serum ferritin concentration and liver iron concentration. This will be measured by the Superconducting Quantum-Interference Device (SQUID) BioSusceptometer. The duration of treatment is 12 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thalassemia Major, Hemosiderosis
Keywords
Iron Overload, Thalassemia, Haemosiderosis, Cardiac, Deferiprone, Chelation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Ferriprox (deferiprone)
Intervention Type
Drug
Intervention Name(s)
Desferal (deferoxamine)
Primary Outcome Measure Information:
Title
To determine whether deferiprone exhibits superior efficacy in removing excess iron from the heart compared to that of deferoxamine, as reflected by MRI T2* assessments in the heart in participants treated with either chelator
Secondary Outcome Measure Information:
Title
To evaluate the relative efficacy of deferiprone with respect to that of deferoxamine as assessed by serum ferritin concentration and liver iron concentration (LIC)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
36 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of thalassemia major as confirmed by laboratory and clinical criteria Participants who are well transfused-maintaining a mean pre-transfusion Hb (hemoglobin) no less than 9 g/dL. Between 18 and 36 years of age. Receiving ongoing chelation therapy with deferoxamine for at least the past five years. Those who have been exposed to deferiprone for ≤ 6 months but not within the last 2 years prior to commencement of this study will be considered eligible to participate. Abnormal heart MRI T2* greater than or equal to 8 ms and < 20 ms. If female, fertile, and is neither pregnant nor lactating, confirms she will use an effective method of contraception for the length of the trial and has a negative pregnancy test immediately prior to commencement of study drug OR has had a tubal ligation OR a hysterectomy OR is post menopausal (at least 1 year no menses prior to enrollment in the study) OR their only sexual partner has been sterilized (if male). If male and fertile, he confirms that he and/or his partner will use an effective method of contraception for the length of the trial. Provide a signed and witnessed written informed consent obtained prior to the first study intervention. Exclusion Criteria: Have anemia other than thalassemia. HIV antibody positive. Clinical evidence of cardiomyopathy as shown by LV Shortening Fraction < 30 % and/or CMR derived LV (left ventricular) Ejection Fraction < 56 %. Severe/significant arrhythmia, including those who have had atrial fibrillation (participants with occasional ectopic beats and normal echo can be included) or those requiring treatment. Previously discontinued therapy with deferiprone or deferoxamine because of an adverse drug reaction to either chelator. Have received deferiprone in the last five years. However those who have been exposed to deferiprone for ≤ 6 months but not within the last 2 years prior to commencement of this study will be considered eligible to participate. Evidence of abnormal liver function (liver enzymes > 3 times upper limit of normal - entry may be delayed until return to normal). Have disorders associated with neutropenia (ANC < 1.5 x 10^9/L) or thrombocytopenia (platelet count <50 x 10^9/L) in the twelve months prior to start of study medication, except for participants who have been treated with interferon and in whom the ANC has fully recovered. Participants with neutropenia or thrombocytopenia in the last year, which resolved with splenectomy, may be considered for this study. Those who refuse to participate in the screening procedures or who are unable to participate in screening procedures or who are unable to comply with requirements of the protocol. Receiving other investigational products. Those in the opinion of the Investigator, who represent poor medical, psychological or psychiatric risks for whom participation in an investigational trial would be unwise. Those who are pregnant, breastfeeding or planning to become pregnant during the study period. Metallic objects in his/her body, such as artificial joints, inner ear (cochlear) implants, brain aneurysm clips, pacemakers, and metallic foreign bodies in the eye or other body areas. History of malignancy. Participants with claustrophobia. History of alcohol or drug abuse. Participants who are, in the opinion of the Investigator, excessively obese.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Renzo Galanello, M.D.
Organizational Affiliation
Ospedale Regionale Microcitemie, Cagliari, Italy
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Antonio Piga, M.D.
Organizational Affiliation
Dipartimento di Scienze Pediatriche e Dell'Adolescenza, University of Turin, Turin, Italy
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Markissia Karagiorga, M.D.
Organizational Affiliation
Aghia Sophia Children's Hospital, Athens, Greece
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Vassilis Ladis, M.D.
Organizational Affiliation
1st Department of Pediatrics, Athens University, Aghia Sophia Children's Hospital, Athens, Greece
Official's Role
Principal Investigator
Facility Information:
Facility Name
1st Department of Pediatrics, Athens University, Aghia Sophia Children's Hospital
City
Athens
ZIP/Postal Code
11527
Country
Greece
Facility Name
Aghia Sophia Children's Hospital
City
Athens
ZIP/Postal Code
11527
Country
Greece
Facility Name
Ospedale Regionale Microcitemie, Dipartimento di Scienze
City
Cagliari
State/Province
Sardegna
ZIP/Postal Code
09100
Country
Italy
Facility Name
Dipartimento di Scienze e Dell' Adolescenza, University of Turin
City
Turin
ZIP/Postal Code
10126
Country
Italy

12. IPD Sharing Statement

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