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| ID | Type | Description | Link |
|---|---|---|---|
| U01HL065260 | U.S. NIH Grant/Contract | View source | |
| U01HL065244 | U.S. NIH Grant/Contract | View source | |
| U01HL065239 | U.S. NIH Grant/Contract | View source | |
| U01HL065238 | U.S. NIH Grant/Contract | View source | |
| U01HL065232 | U.S. NIH Grant/Contract | View source |
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due to low enrollment
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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The purpose of this study is to determine whether left ventricular function improves more rapidly with deferoxamine (DFO) and deferiprone (L1) combination therapy than with DFO monotherapy in patients with thalassemia and decreased ejection fractions. Secondary aims include evaluating changes in myocardial iron burden using T2* and estimating the relative incidence and severity of chelator-induced toxicity.
DESIGN NARRATIVE:
Participants will be randomized to 1 year of treatment with L1/DFO combination therapy or DFO monotherapy. At baseline, 6 months, and 1 year on therapy, cardiac function will be assessed by MRI measurement of left ventricular ejection fraction (LVEF), T2*, Holter monitoring, and electrocardiography. Additional monitoring for safety includes weekly blood testing, monthly visits, and periodic eye and ear exams.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| L1/DFO | Experimental | Deferoxamine (DFO) and deferiprone (L1) combination therapy |
|
| DFO | Active Comparator | Deferoxamine (DFO) monotherapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Deferoxamine | Drug | Deferoxamine will be given daily for 12-24h/day 7 days a week either subcutaneous or intravenous at up to 50-60 mg/kg/day. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Left Ventricular Ejection Fraction (LVEF). | The primary outcome variable is change in left ventricular ejection fraction (blood ejected from the heart into the body) as measured by MRI from baseline to one year. The unit of primary outcome (left ventricular ejection fraction) is the percent of the blood in left ventricle. | Baseline to one year |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate Whether L1/DFO Combination Therapy is Superior to DFO Monotherapy in Lowering Myocardial Iron Burden Estimated by Myocardial T2*. | one year | |
| Change in Left Ventricular (LV) Volume From Screening to One Year. | one year |
Not provided
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John Porter, MD | University College, London | Principal Investigator |
| Patricia J. Giardina, MD | Weill Medical College of Cornell University | Study Chair |
| Ellis J. Neufeld, MD | Boston Children's Hospital | Study Chair |
| Elliott P, Vichinsky, MD | Children's Hospital and Research Institute, Oakland | Study Chair |
| Sonja McKinlay, Ph.D. | New England Research Institutes, Inc. | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Los Angeles | Los Angeles | California | 90027 | United States | ||
| Children's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37975597 | Derived | Padhani ZA, Gangwani MK, Sadaf A, Hasan B, Colan S, Alvi N, Das JK. Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia. Cochrane Database Syst Rev. 2023 Nov 17;11(11):CD011626. doi: 10.1002/14651858.CD011626.pub3. |
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Patients were evaluated for eligibility based on the following criterial. If not eligible, they were not randomized to a treatment arm.
First patient enrolled in August, 2005 and study closed due to low enrollment in June, 2008. 8 participating sites.
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| ID | Title | Description |
|---|---|---|
| FG000 | Deferoxamine (DFO) and Deferiprone (L1) Combination Therapy | DFO + L1 DFO Administered daily at 50-60 mg/kg for 12-24 hr/day 7 days a week either subcutaneous or intravenous. L1 Administered daily at 75 mg/kg in 3 divided doses taken orally and timed so that 2 of 3 doses will be simultaneous with DFO infusion. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Deferiprone (L1) | Drug | The dose of L1, 75mg/kg in three divided oral doses, is the maximum dose at which toxicity has been tested in prospective trials |
|
|
| Change in ECHO LV Volume, Ejection Fraction, Shortening Fraction, and VCFc/Wall Stress Z-score From Baseline to One Year. | one year |
| Change in Holter Monitor Scores From Baseline to One Year. | one year |
| Initiation of or Increase in Cardiac Medications | continuous |
| Adverse Events | continous |
| Oakland |
| California |
| 94609 |
| United States |
| Children's Memorial Hospital | Chicago | Illinois | 60614-3394 | United States |
| Children's Hospital | Boston | Massachusetts | 02115 | United States |
| Weill Medical College of Cornell University | New York | New York | 10021 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104-4399 | United States |
| Deferoxamine (DFO) + Monotherapy |
DFO + Placebo DFO Administered daily at 50-60 mg/kg for 12-24 hr/day 7 days a week either subcutaneous or intravenous. Placebo Administered orally three times daily. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Deferoxamine (DFO) and Deferiprone (L1) Combination Therapy | DFO + L1 DFO Administered daily at 50-60 mg/kg for 12-24 hr/day 7 days a week either subcutaneous or intravenous. L1 Administered daily at 75 mg/kg in 3 divided doses taken orally and timed so that 2 of 3 doses will be simultaneous with DFO infusion. |
| BG001 | Deferoxamine (DFO) + Monotherapy | DFO + Placebo DFO Administered daily at 50-60 mg/kg for 12-24 hr/day 7 days a week either subcutaneous or intravenous. Placebo Administered orally three times daily. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Left Ventricular Ejection Fraction (LVEF). | The primary outcome variable is change in left ventricular ejection fraction (blood ejected from the heart into the body) as measured by MRI from baseline to one year. The unit of primary outcome (left ventricular ejection fraction) is the percent of the blood in left ventricle. | Posted | Least Squares Mean | Standard Error | Percent of the blood in left ventricle | Baseline to one year |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Evaluate Whether L1/DFO Combination Therapy is Superior to DFO Monotherapy in Lowering Myocardial Iron Burden Estimated by Myocardial T2*. | Not Posted | one year | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Left Ventricular (LV) Volume From Screening to One Year. | Not Posted | one year | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in ECHO LV Volume, Ejection Fraction, Shortening Fraction, and VCFc/Wall Stress Z-score From Baseline to One Year. | Not Posted | one year | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Holter Monitor Scores From Baseline to One Year. | Not Posted | one year | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Initiation of or Increase in Cardiac Medications | Not Posted | continuous | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Adverse Events | Not Posted | continous | Participants |
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Deferoxamine (DFO) and Deferiprone (L1) Combination Therapy | DFO + L1 DFO Administered daily at 50-60 mg/kg for 12-24 hr/day 7 days a week either subcutaneous or intravenous. L1 Administered daily at 75 mg/kg in 3 divided doses taken orally and timed so that 2 of 3 doses will be simultaneous with DFO infusion. | 6 | 11 | 8 | 11 | ||
| EG001 | Deferoxamine (DFO) + Monotherapy | DFO + Placebo DFO Administered daily at 50-60 mg/kg for 12-24 hr/day 7 days a week either subcutaneous or intravenous. Placebo Administered orally three times daily. | 3 | 9 | 6 | 9 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abnormal LFTs | Hepatobiliary disorders | CTCAE (3.0) | Systematic Assessment | Nausea & abdominal discomfort occurring while taking deferiprone/placebo. Also reported "muscular type" aches & pains in the upper chest and arms. Severe elevation in liver enzymes was identified. |
|
| Congestive heart failure | Cardiac disorders | CTCAE (3.0) | Non-systematic Assessment | Subject complaint of congestion and bloating. ECHO EF%= 20%, a decrease from 45%. Admitted for higher dose deferoxamine, & management. Deferoxamine was increased to 75 mg/kg/day, 7 days per week over 24 hours. Lasix 40 mg IV x 1 was administered. |
|
| Clot | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment | Pt had arm swelling and ultrasound revealed clot in left PICC line. Pt treated with vancomycin. |
|
| Cellulitis | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | Fever of 102 and cellulitis at the insertion site of his central venous catheter. Redness and pus drained from around this insertion site. The subject received nafcillin and Ceftriaxone IV. Desferal infusion continued during this time. |
|
| Meningitis (unkown viral vs. bacterial) | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | Subject developed a fever 39.2C PO. Creatinine elevated to 2.2. Study drug held. CT without contrast done, "no obvious signs of meningitis or abcess." Treated w/ doses of Vancomycin and Cefotaxime. |
|
| Renal Disease | Renal and urinary disorders | CTCAE (3.0) | Non-systematic Assessment | A routine chemistry showed elevated BUN 30mg/dl and creatinine 1.5mg/dl. |
|
| Palpitation | Cardiac disorders | CTCAE (3.0) | Non-systematic Assessment | Subject complained of palpitations. ECG showed Atrial fibrillation. converting to normal sinus rhythm before started on any medication. |
|
| high grade fever and chills | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | Subject complained of high grade fever and chills associated with dysuria. Subject presented to the ER and prelim results showed urinary tract infection but was admitted for monitoring due to low blood pressure. |
|
| Abdominal Pain | Hepatobiliary disorders | CTCAE (3.0) | Non-systematic Assessment | Subject c/o stomach discomfort. 05/21 ANC was 1.4 and L1/Placebo was stopped. CBC was done and the ANC was 1.9. Treatment was restarted. An MRI (R2/T2*) was performed to assess liver iron. Summary stopped L1/Placebo, stopped DFO-S, MRI performed. |
|
| Pneumonia | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | Subject had been feeling fatigued with episodes of CP. Rx w/ Lasix and aldactone. Subject feeling worse with nausea and vomiting.CT scan showed left lower lobe pneumonia. Started on 10 day course of Levaquin. Discharged in good condition. |
|
| Splenectomy | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment | Subject scheduled her for splenectomy. Had no complications. |
|
| Arrhythmia | Cardiac disorders | CTCAE (3.0) | Non-systematic Assessment | Subject admitted with CHF. Noted tachycardia to 140s. He was in atrial flutter, then atrial fibrillation. Was not hypotensive w/ no evidence of ventricular arrhythmia. Rx and converted to NSR. This event was possibly related to study drug. |
|
| Syncope | Metabolism and nutrition disorders | CTCAE (3.0) | Non-systematic Assessment | Admitted with episode of syncope. His vision became dark and he felt dizzy. He was unable to support himself and fell to the ground hitting the side of his face. He reports that he was conscious throughout. |
|
| Watery diarrhea & hypotension | General disorders | CTCAE (3.0) | Non-systematic Assessment | 5 day history of watery diarrhea. Dx w/ dehydration and syncopal event. |
|
| Retinal toxicity- drug induced | Eye disorders | CTCAE (3.0) | Non-systematic Assessment | Distance vision was blurry and was seen by ophthalmology. ERG analysis shows deficits in both scotopic and photopic responses. These were not present on previous ERG. He c/o blurry vision and could not be corrected with glasses. |
|
| Hyperkalemia | Metabolism and nutrition disorders | CTCAE (3.0) | Non-systematic Assessment | Serum potassium =7.5 meq/L and received calcium carbonate infusion, and normal saline bolus. Glucose rose to 635 mg/dL. History of insulin dependent diabetes. Received Lasix & NS bolus were given. Potassium level returned to normal. |
|
| Central venous line infection | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | Subject was admitted with cellulitis at the insertion site of his central venous catheter. The subject received vancomycin I.V. & developed Redman's syndrome. The vancomycin was stopped and was given Nafcillin IV. |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abnormal LFTs | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Bilerateral Hip Pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Chest Ache | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Common Cold | Social circumstances | CTCAE (3.0) | Non-systematic Assessment |
| |
| Dizziness | General disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Epistaxis | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Fanconi | Pregnancy, puerperium and perinatal conditions | CTCAE (3.0) | Systematic Assessment |
| |
| Fever | General disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Kicked in chest | Social circumstances | CTCAE (3.0) | Non-systematic Assessment |
| |
| Low Grade Fever and Sore Throay | General disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Nausea and Vomiting | General disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Otitis media | Nervous system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Palpitations with dizziness | Cardiac disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Phlebotic pain at blood infusion | Injury, poisoning and procedural complications | CTCAE (3.0) | Non-systematic Assessment |
| |
| Sternocleidomastoid muscle spasm | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| sore throat | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Strep Throat | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment |
| |
| Upper Respiratory Infection | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Vertigo | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Vomiting | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Allergic transfusion reactions hives | Injury, poisoning and procedural complications | CTCAE (3.0) | Systematic Assessment |
| |
| sore throat and cough | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| stomach flu | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| tooth ache | Injury, poisoning and procedural complications | CTCAE (3.0) | Non-systematic Assessment |
| |
| Anxiety attack | Psychiatric disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Heart palpatations | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
| |
| stomach discomfort | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Urinary Tract Infection | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Shortness of Breath/fatigue | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Ankle pain | Injury, poisoning and procedural complications | CTCAE (3.0) | Non-systematic Assessment |
| |
| Abdominal Bloating | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
|
The study was stopped early by NHLBI when analysis of the interim data confirmed a required sample size of 86 that was not achievable within the required time frame within the participating or planned centres.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John Porter, MD, Principal Investigator | UCL Cancer Institute | +011 (44) 207 679 6224 | j.porter@ucl.ac.uk |
| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D017086 | beta-Thalassemia |
| ID | Term |
|---|---|
| D013789 | Thalassemia |
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
Not provided
Not provided
| ID | Term |
|---|---|
| D003676 | Deferoxamine |
| D000077543 | Deferiprone |
| D020084 | Long Interspersed Nucleotide Elements |
| ID | Term |
|---|---|
| D006877 | Hydroxamic Acids |
| D006898 | Hydroxylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D006880 | Hydroxy Acids |
| D002264 | Carboxylic Acids |
| D011728 | Pyridones |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D018626 | Retroelements |
| D020071 | Interspersed Repetitive Sequences |
| D012091 | Repetitive Sequences, Nucleic Acid |
| D001483 | Base Sequence |
| D015394 | Molecular Structure |
| D001669 | Biochemical Phenomena |
| D055598 | Chemical Phenomena |
| D040342 | Genetic Structures |
| D055614 | Genetic Phenomena |
| D040481 | Genome Components |
| D016678 | Genome |
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| >=65 years |
|
| Male |
|
| United States |
|
| Lebanon |
|