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To allow patients treated with deferasirox in the core study to continue iron chelation therapy for 2 years or until the drug became locally commercially available. To evaluate the long-term safety and efficacy of deferasirox by measuring treatment success, change in liver iron content (LIC) and change in serum ferritin levels. Safety was mainly assessed by incidence of adverse events (AEs)and clinically significant lab parameters.
Iron accumulation is an inevitable consequence of chronic blood transfusions and results in serious complications in the absence of chelation treatment to remove excess iron. Deferasirox (Exjade, ICL670) is an oral chelator with high iron-binding potency and selectivity. This extension study aimed at collecting efficacy and safety data during 2 years of treatment with deferasirox in the extension study or until deferasirox became commercially available in the countries where the centers were located, whichever came first. The population comprised of β-thalassemia patients with transfusional hemosiderosis who could not be satisfactorily treated with deferoxamine or deferiprone.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Deferasirox | Experimental | Deferasirox was given orally once daily (10 to 20 mg/kg) to participants 2 years and older based on participant's body weight. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Deferasirox | Drug | Deferasirox was administered orally once daily. Deferasirox was available as 125 mg, 250 mg, and 500 mg tablets. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Treatment Success From Core Baseline (BL) to Extension End of Study, by Baseline LIC Level and Age | Success was defined as the percentage of participants with decreased liver iron content (LIC) at the end of extension study compared to core baseline (BL) LIC. Success Criteria: For participants with Baseline LIC from 1 - <7 mg Fe/g dw, success was achieved if LIC level maintained at 1 - <7 mg Fe/g dw. For participants with Baseline LIC ≥7 - <10 mg Fe/g dw, success was achieved if LIC dropped to between 1 and < 7 mg Fe/g dw. For participants with Baseline LIC ≥10 mg Fe/g dw, success was achieved if LIC dropped by at least 3 mg Fe/g dw. LIC was measured by biopsy or magnetic resonance imaging. | From Core Study Baseline, to Extension End of Study, Up to 3 Years |
| Absolute Change in Liver Iron Concentration (LIC)Measured by Liver MRI or Liver Biopsy From Core Study Baseline (BL) to End of Extension Study, by LIC Category | Liver MRI or Liver Biopsy was performed at the core study baseline (BL) and then 1 year and 2 years in the core study, baseline of the extension study and time of discontinuation from the extension visit (end of study). Liver iron content (LIC) is reported in milligram Iron per gram dry weight (mg Fe/g dw). Absolute change in LIC from core study baseline to the end of the extension study is presented for participants with the following two core study baseline LIC levels: 1-<7 mg Fe/g dw and ≥7 mg Fe/g dw. | From Baseline of Core Study to End of Extension Study, up to 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Absolute Change in Serum Ferritin Level Measured From Core Study Baseline (BL) to End of Extension Study | Serum Levels were assessed at core study baseline (BL), 1 year, 2 years in core study, baseline of extension study and time of discontinuation from the extension visit (end of study) in monthly intervals. Serum Ferritin is reported in micrograms per Liter (µg/L). | From Baseline of Core Study to End of Extension Study, up to 3 years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Cairo | Egypt | ||||
| Novartis Investigative Site |
2 participants from the 16 and older group did not receive deferasirox. Thus, the 16 and older group comprises of 69 treated participants.
This is an Extension to Core Study CICL670A2402 (NCT00171171). 233 participants completed the core study and entered this extension study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Deferasirox (Between 2 <16 Years ) | Participants age 2 years up to 16 years received a daily oral dose of deferasirox. Dose selection was based on the dose last received in the core study. The individual daily doses of deferasirox and the exact amount of tablets (125, 250, or 500 mg) contributing to each dose were calculated by the investigator based on the patient's body weight. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Absolute Change in Serum Ferritin Level for All Participants Measured From Core Study Baseline (BL) to End of Extension Study, by Baseline Liver Iron Content (LIC) | Serum Levels were assessed at core study baseline (BL) and then 1 year and 2 years in core study, baseline of extension study and time of discontinuation from the extension visit (end of study). Serum Ferritin is reported in micrograms per Liter. Absolute change in Serum Ferritin from core study baseline to the end of the extension study is presented for participants with the following two core study baseline LIC levels: 1-<7 mg Fe/g dw and ≥7 mg Fe/g dw. | From Baseline of Core Study to End of Extension Study, up to 3 years |
| Beirut |
| Lebanon |
| Novartis Investigative Site | Muscat | Oman |
| Novartis Investigative Site | Riyadh | Saudi Arabia |
| Novartis Investigative Site | Damascus | Syria |
| FG001 | Deferasirox (16 Years or Older) | Participants age 16 years or older received a daily oral dose of deferasirox. Dose selection was based on the dose last received in the core study. The individual daily doses of deferasirox and the exact amount of tablets (125, 250, or 500 mg) contributing to each dose were calculated by the investigator based on the patient's body weight. |
| Received Deferasirox |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Deferasirox (Between 2 <16 Years ) | Participants age 2 years up to 16 years received a daily oral dose of deferasirox. Dose selection was based on the dose last received in the core study. The individual daily doses of deferasirox and the exact amount of tablets (125, 250, or 500 mg) contributing to each dose were calculated by the investigator based on the patient's body weight. |
| BG001 | Deferasirox (16 Years or Older) | Participants age 16 years or older received a daily oral dose of deferasirox. Dose selection was based on the dose last received in the core study. The individual daily doses of deferasirox and the exact amount of tablets (125, 250, or 500 mg) contributing to each dose were calculated by the investigator based on the patient's body weight. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Safety Population consisting of all participants who received study drug in the Extension study n= 231. | Mean | Standard Deviation | years |
| ||||||||||||||
| Sex/Gender, Customized | Safety Population consisting of all participants who received study drug in the Extension study n=231. | Number | participants |
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| 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 | Percentage of Participants With Treatment Success From Core Baseline (BL) to Extension End of Study, by Baseline LIC Level and Age | Success was defined as the percentage of participants with decreased liver iron content (LIC) at the end of extension study compared to core baseline (BL) LIC. Success Criteria: For participants with Baseline LIC from 1 - <7 mg Fe/g dw, success was achieved if LIC level maintained at 1 - <7 mg Fe/g dw. For participants with Baseline LIC ≥7 - <10 mg Fe/g dw, success was achieved if LIC dropped to between 1 and < 7 mg Fe/g dw. For participants with Baseline LIC ≥10 mg Fe/g dw, success was achieved if LIC dropped by at least 3 mg Fe/g dw. LIC was measured by biopsy or magnetic resonance imaging. | The primary analysis will be on the intent-to-treat (ITT) population. ITT population includes all participants who performed the core end of study (EOS) visit evaluation and assessments and were included in the extension study. "n" is the number of participants analyzed in each category. | Posted | Mean | 95% Confidence Interval | percentage of participants | From Core Study Baseline, to Extension End of Study, Up to 3 Years |
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| Primary | Absolute Change in Liver Iron Concentration (LIC)Measured by Liver MRI or Liver Biopsy From Core Study Baseline (BL) to End of Extension Study, by LIC Category | Liver MRI or Liver Biopsy was performed at the core study baseline (BL) and then 1 year and 2 years in the core study, baseline of the extension study and time of discontinuation from the extension visit (end of study). Liver iron content (LIC) is reported in milligram Iron per gram dry weight (mg Fe/g dw). Absolute change in LIC from core study baseline to the end of the extension study is presented for participants with the following two core study baseline LIC levels: 1-<7 mg Fe/g dw and ≥7 mg Fe/g dw. | Participants from the Intent-to-Treat (ITT) population for whom LIC data was available at Core Study baseline and at the End of Extension Study. "n" is the number of participants analyzed in each category. | Posted | Mean | Standard Deviation | mg Fe/g dw | From Baseline of Core Study to End of Extension Study, up to 3 years |
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| Secondary | Absolute Change in Serum Ferritin Level Measured From Core Study Baseline (BL) to End of Extension Study | Serum Levels were assessed at core study baseline (BL), 1 year, 2 years in core study, baseline of extension study and time of discontinuation from the extension visit (end of study) in monthly intervals. Serum Ferritin is reported in micrograms per Liter (µg/L). | Participants from the Intent-to-Treat (ITT) population for whom Serum Ferritin data was available at Core Study baseline and at the End of Extension Study. | Posted | Mean | Standard Deviation | µg/L | From Baseline of Core Study to End of Extension Study, up to 3 years |
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| Secondary | Absolute Change in Serum Ferritin Level for All Participants Measured From Core Study Baseline (BL) to End of Extension Study, by Baseline Liver Iron Content (LIC) | Serum Levels were assessed at core study baseline (BL) and then 1 year and 2 years in core study, baseline of extension study and time of discontinuation from the extension visit (end of study). Serum Ferritin is reported in micrograms per Liter. Absolute change in Serum Ferritin from core study baseline to the end of the extension study is presented for participants with the following two core study baseline LIC levels: 1-<7 mg Fe/g dw and ≥7 mg Fe/g dw. | Participants from the Intent-to-Treat (ITT) population for whom Serum Ferritin data was available at Core Study baseline and at the End of Extension Study. "n" is the number of participants analyzed in each category. | Posted | Mean | Standard Deviation | µg/L | From Baseline of Core Study to End of Extension Study, up to 3 years |
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|
From baseline to end of study, up to 2 years
Adverse Events were calculated for the Safety Population consisting of all participants who received study drug in this Extension study. (162 participants between 2 < 16 years, 69 participants 16 years or older. Total 231 participants in Safety Population.)
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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 | Deferasirox (Between 2 <16 Years) | Participants age 2 years up to 16 years received a daily oral dose of deferasirox. Dose selection was based on the dose last received in the core study. The individual daily doses of deferasirox and the exact amount of tablets (125, 250, or 500 mg) contributing to each dose were calculated by the investigator based on the patient's body weight. | 5 | 162 | 54 | 162 | ||
| EG001 | Deferasirox (16 Years or Older) | Participants age 16 years and older received a daily oral dose of deferasirox. Dose selection was based on the dose last received in the core study. The individual daily doses of deferasirox and the exact amount of tablets (125, 250, or 500 mg) contributing to each dose were calculated by the investigator based on the patient's body weight. | 12 | 69 | 33 | 69 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arrhythmia | Cardiac disorders | MedDRA | Systematic Assessment |
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| Cardiac failure | Cardiac disorders | MedDRA | Systematic Assessment |
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| Cardiac failure congestive | Cardiac disorders | MedDRA | Systematic Assessment |
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| Cardio-respiratory arrest | Cardiac disorders | MedDRA | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Intestinal obstruction | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Melaena | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Peptic ulcer perforation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA | Systematic Assessment |
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| Cholecystitis | Hepatobiliary disorders | MedDRA | Systematic Assessment |
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| Appendicitis | Infections and infestations | MedDRA | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
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| Otitis media | Infections and infestations | MedDRA | Systematic Assessment |
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| Perinephric abscess | Infections and infestations | MedDRA | Systematic Assessment |
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| Pneumonia streptococcal | Infections and infestations | MedDRA | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA | Systematic Assessment |
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| Subdiaphragmatic abscess | Infections and infestations | MedDRA | Systematic Assessment |
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| Wound infection | Infections and infestations | MedDRA | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
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| Femur fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
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| Hip fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
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| Perinephric collection | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
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| Road traffic accident | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
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| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA | Systematic Assessment |
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| Cerebral haemorrhage | Nervous system disorders | MedDRA | Systematic Assessment |
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| Coma | Nervous system disorders | MedDRA | Systematic Assessment |
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| Convulsion | Nervous system disorders | MedDRA | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
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| Subarachnoid haemorrhage | Nervous system disorders | MedDRA | Systematic Assessment |
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| Adenoidal hypertrophy | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
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| Aneurysm | Vascular disorders | MedDRA | Systematic Assessment |
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| Haemorrhage | Vascular disorders | MedDRA | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Pain | General disorders | MedDRA | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA | Systematic Assessment |
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| Blood calcium decreased | Investigations | MedDRA | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA | Systematic Assessment |
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| Osteoporosis | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
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An internal review revealed major Good Clinical Practice violations at 2 sites in Saudi Arabia: 602 for core + extension, 601 for 2-yr extension. Therefore data was excluded (completely for 602 + partly for 601) from analyses.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 |
| ID | Term |
|---|---|
| D017086 | beta-Thalassemia |
| D006486 | Hemosiderosis |
| D019190 | Iron Overload |
| 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 |
| D019189 | Iron Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000077588 | Deferasirox |
| ID | Term |
|---|---|
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Male |
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| Core Baseline LIC ≥10 mg Fe/g dw (n=124, 61) |
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