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| ID | Type | Description | Link |
|---|---|---|---|
| R34HL127162 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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This is a pilot study, single-blind, randomized, multicenter, therapeutic clinical trial designed to evaluate the feasibility of enrolling infants and toddlers (9 months to 36 months) with sickle cell anemia (SCA; HbSS or HbSβ^0thalassemia), regardless of disease severity, to a therapeutic trial. A prior clinical trial at St. Jude Children's Research Hospital (SJCRH) (BABYHUG, NCT01783990) demonstrated that a fixed dose (20 mg/kg/day) of hydroxyurea was safe and effective in decreasing SCA-related complications in very young children (9-18 months), and largely due to these findings, hydroxyurea is recommended to be offered to all children (≥9 months old) with SCA, independent of disease severity. Nevertheless, children in the treatment arm of BABYHUG continued to experience vaso-occlusive symptoms and to incur organ damage. In clinical trials of older children with SCA, intensification of hydroxyurea to a maximum tolerated dosage (MTD), defined by mild to moderate myelosuppression, may be associated with improved laboratory parameters compared to fixed lower-dosing, but the clinical benefits gained from dose intensification have not been described. Therefore, in this trial, children in the standard treatment arm will receive a fixed dose of hydroxyurea (20 mg/kg/day), and participants in the experimental arm will receive hydroxyurea intensified to MTD, defined by a goal absolute neutrophil count (ANC) of 1500-3000 cells/µL. This trial aims to establish a multicenter infrastructure that will identify, enroll and randomize very young children (9-36 months) to receive fixed dose versus intensified-dose hydroxyurea in a single blinded manner, and to obtain prospective pilot data comparing the clinical and laboratory outcomes between the treatment arms to facilitate design of a definitive phase III trial.
All participants will initially receive hydroxyurea at a dose of ~20 mg/kg/day in an open label fashion for eight weeks (± 2 weeks) prior to randomization. Participants will receive monthly medical evaluations (every 4 ± 2 weeks) where they will have height and weight measurements, medical history, physical examination, and medication adherence assessments. During these monthly visits complete blood counts with absolute reticulocyte count will be monitored. Hemoglobin electrophoresis, complete serum chemistries, urinalysis, lactate dehydrogenase and quality of life measurements will be obtained every 20 (±2) weeks. Transcranial Doppler (TCD) ultrasound velocities will be obtained at study entry (in participants ≥2 years of age) and study exit. Participants randomized to receive hydroxyurea at MTD will have their dose increased by 5 mg/kg/day every 8 weeks, in the absence of toxicity, until a goal ANC of 1500-3000 cells/µL is achieved, up to a maximum of 35 mg/kg/day.
Both groups will receive their assigned treatment for 48 weeks (± 3 weeks). Participants will be in the study for a total of 56 weeks (± 3 weeks) and have 14 clinic visits to the St. Jude outpatient Hematology Clinic during that time. After the 56 weeks, participants will be followed for an additional 30 days for side effects and will then be taken off study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Stable Dosing | Active Comparator | In the first 8 weeks (± 2 weeks) of this study, participants will receive standard treatment [a fixed dose of 20 (± 2.5) mg/kg/day of hydroxyurea]. After 8 weeks (± 2 weeks) of standard treatment, participants will be randomized (like flipping a coin) to one of two treatment groups. Group 1 (Stable Dosing) continues standard treatment. |
|
| Intensive Dosing | Experimental | In the first 8 weeks (± 2 weeks) of this study, participants will receive standard treatment [a fixed dose of 20 (± 2.5) mg/kg/day of hydroxyurea]. After 8 weeks (± 2 weeks) of standard treatment, participants will be randomized (like flipping a coin) to one of two treatment groups. Group 2 (Intensive Dosing) will have their HU dose increased by 5 mg/kg/day every 8 weeks up to a maximum of 35 mg/kg/day. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hydroxyurea | Drug | Given orally once daily. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients Enrolled. | A count of the number of patients enrolled will be provided. | at baseline |
| Number of Patients Randomized | A count of the number of patients randomized will be provided. | Eight weeks (± 2 weeks) after study enrollment |
| Number of Randomized Patients With ≥80% Chronic Medication Compliance | Chronic medication compliance is defined based on medication possession ratio (MPR), a measure of the percentage of time that a patient has access to medication. Each participant's MPR is calculated as [(days medication in family's possession/days prescribed medication) * 100]. | At completion of therapy, up to 56 weeks after study enrollment |
| Number of Patients Who Have the % Fetal Hemoglobin (%HbF) Collected at Baseline and at Study Exit | The number of patients who have successfully provided %HbF at baseline and study exit will be provided. | At baseline and at completion of the protocol, up to 56 weeks after study enrollment |
| Measure | Description | Time Frame |
|---|---|---|
| Frequency by Reason Given for Refusal for Study Participation | Descriptive statistics of count and frequency will be provided for participants who were approached but refused to be enrolled on the study. | Once, at enrollment |
| Number of Patients With Hospitalizations by Arm |
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Inclusion Criteria:
Exclusion Criteria:
Permanent:
Transient (participants may be re-evaluated after ≥14 days):
Recent (<30 days) participation in another clinical intervention trial utilizing an investigational new drug/investigational device exemption (IND/IDE) agent.
Erythrocyte transfusion in the past 2 months.
Laboratory Assessments:
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| Name | Affiliation | Role |
|---|---|---|
| Jeremie Estepp, MD | St. Jude Children's Research Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University/Children's Health Care of Atlanta | Atlanta | Georgia | 30322 | United States | ||
| University of Mississippi Medical Center |
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| Label | URL |
|---|---|
| St. Jude Children's Research Hospital | View source |
| Clinical Trials Open at St. Jude | View source |
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Participants without toxicity or with toxicity which requires discontinuation of hydroxyurea (HU) but resolved and participant continuing HU during those eight weeks (±2 weeks), were randomized to receive standard or intensive therapy based on a block randomization (block size of 4 used in each stratum) stratified by clinical center and by baseline age of the participant (9 to <24 months and 24 to 36 months) because of the natural physiologic decline of HbF with increasing age.
The study planned to enroll up to 65 children with sickle cell anemia (SCA) to get 50 randomized in a 27-month period. All eligible participants who consented were enrolled on the study. The duration of the study is based on sample size of 50 patients randomized and/or 27-month period, whichever comes first. Actual recruitment occurred 5/3/2017 to 6/3/2019 and 58 subjects were enrolled to yield 51 randomized at 4 clinical centers.
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| ID | Title | Description |
|---|---|---|
| FG000 | Stable Dosing | In the first 8 weeks (± 2 weeks) of this study, participants will receive standard treatment [a fixed dose of 20 (± 2.5) mg/kg/day of hydroxyurea]. After 8 weeks (± 2 weeks) of standard treatment, participants will be randomized (like flipping a coin) to one of two treatment groups. Group 1 (Stable Dosing) continues standard treatment. |
| FG001 | Intensive Dosing | In the first 8 weeks (± 2 weeks) of this study, participants will receive standard treatment [a fixed dose of 20 (± 2.5) mg/kg/day of hydroxyurea]. After 8 weeks (± 2 weeks) of standard treatment, participants will be randomized (like flipping a coin) to one of two treatment groups. Group 2 (Intensive Dosing) will have their HU dose increased by 5 mg/kg/day every 8 weeks up to a maximum of 35 mg/kg/day. |
| FG002 | Non-Randomized | Participants who came off study prior to randomization |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Stable Dosing | In the first 8 weeks (± 2 weeks) of this study, participants will receive standard treatment [a fixed dose of 20 (± 2.5) mg/kg/day of hydroxyurea]. After 8 weeks (± 2 weeks) of standard treatment, participants will be randomized (like flipping a coin) to one of two treatment groups. Group 1 (Stable Dosing) continues standard treatment. Hydroxyurea: Given orally once daily. |
| 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 |
| 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 | Number of Patients Enrolled. | A count of the number of patients enrolled will be provided. | 58 subjects enrolled on study. Of those, n=7 came off study prior to randomization (N=2 came off study due to PI discretion, n=4 came off study due to Parent/guardian/patient choice, and n=1 was a screen failure (HBG)). The remaining n=51 were randomized. | Posted | Count of Participants | Participants | at baseline |
|
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Subjects in both treatment arms will be followed for a maximum of 56 weeks regardless of the actual number of study visits. Upon completion of the 56 weeks, patients will be followed for an additional 30 days for toxicities and will then be taken off study.
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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 | Stable Dosing - Post Randomization | In the first 8 weeks (± 2 weeks) of this study, participants will receive standard treatment [a fixed dose of 20 (± 2.5) mg/kg/day of hydroxyurea]. After 8 weeks (± 2 weeks) of standard treatment, participants will be randomized (like flipping a coin) to one of two treatment groups. Group 1 (Stable Dosing) continues standard treatment. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Platelet count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jeremie Estepp, MD | St. Jude Children's Research Hospital | (901) 595-5703 | jeremie.estepp@stjude.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 9, 2020 | May 6, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
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| ID | Term |
|---|---|
| D006918 | Hydroxyurea |
| ID | Term |
|---|---|
| D014508 | Urea |
| D000577 | Amides |
| D009930 | Organic Chemicals |
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The number of patients with hospitalizations will be provided by arm. This analysis approach is different than what was written in the protocol due to small number of participants with hospitalizations and small number of hospitalization events. |
| From baseline through completion of therapy, up to 56 weeks |
| Cumulative Number of Hospitalizations by Arms | The total number of hospitalization events will be provided by arms. This analysis approach is different than what was written in the protocol due to small number of participants with hospitalizations and small number of hospitalization events. | From baseline through completion of therapy, up to 56 weeks |
| Mean Change in Hemoglobin (g/dL) | Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Median Change in Hemoglobin (g/dL) | Descriptive statistics of the change between baseline and completion of the study will be provided. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Mean Change in Fetal Hemoglobin (%) | Descriptive statistics of the change between baseline and completion of the study will be provided. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Median Change in Fetal Hemoglobin (%) | Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Mean Change in Mean Corpuscular Volume (fL) | Descriptive statistics of the change between baseline and completion of the study will be provided. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Median Change in Mean Corpuscular Volume (fL) | Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Mean Change in Absolute Reticulocyte Count (*10^3 Reticulocytes/µL) | Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Median Change in Absolute Reticulocyte Count (*10^3 Reticulocytes/µL) | Descriptive statistics of the change between baseline and completion of the study will be provided. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Mean Change in White Blood Cell Count (*10^3 White Blood Cells/µL) | Descriptive statistics of the change between baseline and completion of the study will be provided. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Median Change in White Blood Cell Count (*10^3 White Blood Cells/µL) | Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Mean Change in Absolute Neutrophil Count (*10^3 Neutrophils/µL) | Descriptive statistics of the change between baseline and completion of the study will be provided. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Median Change in Absolute Neutrophil Count (*10^3 Neutrophils/µL) | Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Mean Change in Platelet Count (*10^3 Platelets/µL) | Descriptive statistics of the change between baseline and completion of the study will be provided. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Median Change in Platelet Count (*10^3 Platelets/µL) | Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Mean Change in Bilirubin (mg/dL) | Descriptive statistics of the change between baseline and completion of the study will be provided. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Median Change in Bilirubin (mg/dL) | Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Mean Change in Lactate Dehydrogenase (Units/L) | Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Median Change in Lactate Dehydrogenase (Units/L) | Descriptive statistics of the change between baseline and completion of the study will be provided. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Number of Participants Who do Not Have Normal Transcranial Doppler (TCD) Ultrasound Velocities | Normal TCD velocities will be defined as TCD velocities <170 cm/s. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Number of Participants Who Undergo Surgery | Any operative procedure will be included. | From start of therapy through completion of therapy, up to 56 weeks |
| Number of Participants Who Undergo Transfusion | Transfusion will be defined as the provision of red blood cells to correct anemia. | From start of therapy through completion of therapy, up to 56 weeks |
| Number of Patients With Toxicities Related to Hydroxyurea Dosing | Number of patients with toxicities to include: neutropenia (ANC <1000*/µL), reticulocytopenia (ARC <80*10^3/µL and concomitant anemia (hemoglobin <6 g/dL), and thrombocytopenia (platelets <100*10^3/µL). | From start of therapy through completion of therapy, up to 56 weeks |
| Number of Toxicities Related to Hydroxyurea Dosing | Number of toxicities will be reported to include: neutropenia (ANC <1000*/µL), reticulocytopenia (ARC <80*10^3/µL and concomitant anemia (hemoglobin <6 g/dL), and thrombocytopenia (platelets <100*10^3/µL). | From start of therapy through completion of therapy, up to 56 weeks |
| Change in Pain and Hurt Score | Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Change in Pain Impact Score | Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Change in Pain Management Score | Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Change in Worry I Score | Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Change in Worry II Score | Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Change in Emotions Score | Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Change in Treatment Score | Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Change in Communication I Score | Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Change in Communication II Score | Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score. | From baseline at study entry to completion of therapy, up to 56 weeks |
| Jackson |
| Mississippi |
| 39216 |
| United States |
| St. Jude Children's Research Hospital | Memphis | Tennessee | 38105 | United States |
| University of Texas Southwestern Medical Center at Dallas | Dallas | Texas | 75390-9063 | United States |
| Screen failure |
|
| Death |
|
| Lost to Follow-up |
|
| BG001 | Intensive Dosing | In the first 8 weeks (± 2 weeks) of this study, participants will receive standard treatment [a fixed dose of 20 (± 2.5) mg/kg/day of hydroxyurea]. After 8 weeks (± 2 weeks) of standard treatment, participants will be randomized (like flipping a coin) to one of two treatment groups. Group 2 (Intensive Dosing) will have their HU dose increased by 5 mg/kg/day every 8 weeks up to a maximum of 35 mg/kg/day. Hydroxyurea: Given orally once daily. |
| BG002 | Non-Randomized Patients | Patients who came off study prior to randomization |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | months |
|
| Age, Continuous | Mean | Standard Deviation | months |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
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| Primary | Number of Patients Randomized | A count of the number of patients randomized will be provided. | Fifty-one were randomized out of the 58 enrolled. | Posted | Count of Participants | Participants | Eight weeks (± 2 weeks) after study enrollment |
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| Primary | Number of Randomized Patients With ≥80% Chronic Medication Compliance | Chronic medication compliance is defined based on medication possession ratio (MPR), a measure of the percentage of time that a patient has access to medication. Each participant's MPR is calculated as [(days medication in family's possession/days prescribed medication) * 100]. | There were 51 subjects randomized to treatment of which 42 completed the protocol therapy. MPR was calculated on the full study period. The n=9 patients that were withdrawn were counted as <80% chronic medical compliance. Of the n=42 patients that completed protocol treatment, n=41 had ≥80% chronic medication compliance. | Posted | Count of Participants | Participants | At completion of therapy, up to 56 weeks after study enrollment |
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| Primary | Number of Patients Who Have the % Fetal Hemoglobin (%HbF) Collected at Baseline and at Study Exit | The number of patients who have successfully provided %HbF at baseline and study exit will be provided. | N=42 patients completed the protocol therapy and had labs collected at exit visit. | Posted | Number | Participants | At baseline and at completion of the protocol, up to 56 weeks after study enrollment |
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| Secondary | Frequency by Reason Given for Refusal for Study Participation | Descriptive statistics of count and frequency will be provided for participants who were approached but refused to be enrolled on the study. | n=154 subjects declined to participate in HUGKISS and provided the following reasons for declining to participate. | Posted | Count of Participants | Participants | Once, at enrollment |
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|
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| Secondary | Number of Patients With Hospitalizations by Arm | The number of patients with hospitalizations will be provided by arm. This analysis approach is different than what was written in the protocol due to small number of participants with hospitalizations and small number of hospitalization events. | The n=51 subjects that were randomized to treatment. | Posted | Count of Participants | Participants | From baseline through completion of therapy, up to 56 weeks |
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|
|
| Secondary | Cumulative Number of Hospitalizations by Arms | The total number of hospitalization events will be provided by arms. This analysis approach is different than what was written in the protocol due to small number of participants with hospitalizations and small number of hospitalization events. | The n=51 subjects that were randomized to treatment. | Posted | Number | hospitalizations | From baseline through completion of therapy, up to 56 weeks |
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| Secondary | Mean Change in Hemoglobin (g/dL) | Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test. | Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard arm.) N=42 subjects completed protocol therapy (n=23 to the intensive arm and n=19 to the standard arm.) All n=42 that completed the study had HGB measurements at both baseline and at exit visit. | Posted | Mean | Standard Deviation | g/dL | From baseline at study entry to completion of therapy, up to 56 weeks |
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|
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| Secondary | Median Change in Hemoglobin (g/dL) | Descriptive statistics of the change between baseline and completion of the study will be provided. | Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard arm.) N=42 subjects completed protocol therapy (n=23 to the intensive arm and n=19 to the standard arm.) All n=42 that completed the study had hemoglobin (HGB) measurements at both baseline and at exit visit. | Posted | Median | Full Range | g/dL | From baseline at study entry to completion of therapy, up to 56 weeks |
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|
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| Secondary | Mean Change in Fetal Hemoglobin (%) | Descriptive statistics of the change between baseline and completion of the study will be provided. | Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) All 42 that completed the study had Hemoglobin F (HbF) measurements at both baseline and at exit visit. | Posted | Mean | Standard Deviation | percentage of Hemoglobin F | From baseline at study entry to completion of therapy, up to 56 weeks |
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|
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| Secondary | Median Change in Fetal Hemoglobin (%) | Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test. | Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) All 42 that completed the study had Hemoglobin F (Hbf) measurements at both baseline and at exit visit. | Posted | Median | Full Range | percentage of Hemoglobin F | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Mean Change in Mean Corpuscular Volume (fL) | Descriptive statistics of the change between baseline and completion of the study will be provided. | Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) All 42 that completed the study had mean corpuscular volume (MCV) measurements at both baseline and exit visits. | Posted | Mean | Standard Deviation | fL | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Median Change in Mean Corpuscular Volume (fL) | Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test. | Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) All 42 that completed the study had mean corpuscular volume (MCV) measurements at both baseline and exit visits. | Posted | Median | Full Range | fL | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Mean Change in Absolute Reticulocyte Count (*10^3 Reticulocytes/µL) | Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test. | Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) N=41 of the n=42 subjects that completed the study had absolute reticulocyte count (ARC) measurements at both baseline and exit visits. | Posted | Mean | Standard Deviation | *10^3 reticulocytes/µL | From baseline at study entry to completion of therapy, up to 56 weeks |
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|
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| Secondary | Median Change in Absolute Reticulocyte Count (*10^3 Reticulocytes/µL) | Descriptive statistics of the change between baseline and completion of the study will be provided. | Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) N=41 of the n=42 subjects that completed the study had absolute reticulocyte count (ARC) measurements at both baseline and exit visits. | Posted | Median | Full Range | *10^3 reticulocytes/µL | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Mean Change in White Blood Cell Count (*10^3 White Blood Cells/µL) | Descriptive statistics of the change between baseline and completion of the study will be provided. | Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) All 42 that completed the study had white blood cell (WBC) measurements at both baseline and exit visits. | Posted | Mean | Standard Deviation | *10^3 white blood cells/µL | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Median Change in White Blood Cell Count (*10^3 White Blood Cells/µL) | Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test. | Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) All 42 that completed the study had white blood cell (WBC) measurements at both baseline and exit visits. | Posted | Median | Full Range | *10^3 white blood cells/µL | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Mean Change in Absolute Neutrophil Count (*10^3 Neutrophils/µL) | Descriptive statistics of the change between baseline and completion of the study will be provided. | Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) N=41 of the 42 that completed the study had absolute neutrophil count (ANC) measurements at both baseline and exit visits. | Posted | Mean | Standard Deviation | *10^3 neutrophils/µL | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Median Change in Absolute Neutrophil Count (*10^3 Neutrophils/µL) | Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test. | Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) N=41 of the 42 that completed the study had absolute neutrophil count (ANC) measurements at both baseline and exit visits. | Posted | Median | Full Range | *10^3 neutrophils/µL | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Mean Change in Platelet Count (*10^3 Platelets/µL) | Descriptive statistics of the change between baseline and completion of the study will be provided. | Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) All 42 that completed the study had platelet (PLT) measurements at both baseline and exit visits. | Posted | Mean | Standard Deviation | *10^3 platelets/µL | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Median Change in Platelet Count (*10^3 Platelets/µL) | Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test. | Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) All 42 that completed the study had platelet (PLT) measurements at both baseline and exit visits. | Posted | Median | Full Range | *10^3 platelets/µL | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Mean Change in Bilirubin (mg/dL) | Descriptive statistics of the change between baseline and completion of the study will be provided. | Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) Of the 42 that completed the study, n=40 had bilirubin measurements at both baseline and exit visits. | Posted | Mean | Standard Deviation | mg/dL | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Median Change in Bilirubin (mg/dL) | Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test. | Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) Of the 42 that completed the study, n=40 had bilirubin measurements at both baseline and exit visits. | Posted | Median | Full Range | mg/dL | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Mean Change in Lactate Dehydrogenase (Units/L) | Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test. | Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) Of the 42 that completed the study, n=41 had lactate dehydrogenase (LDH) measurements at both baseline and exit visits. | Posted | Mean | Standard Deviation | units/L | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Median Change in Lactate Dehydrogenase (Units/L) | Descriptive statistics of the change between baseline and completion of the study will be provided. | Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) Of the 42 that completed the study, n=41 had lactate dehydrogenase (LDH) measurements at both baseline and exit visits. | Posted | Median | Full Range | units/L | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Number of Participants Who do Not Have Normal Transcranial Doppler (TCD) Ultrasound Velocities | Normal TCD velocities will be defined as TCD velocities <170 cm/s. | Subjects that complete protocol therapy and have TCD ultrasound at exit visit. N=42 subjects completed protocol therapy. | Posted | Count of Participants | Participants | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Number of Participants Who Undergo Surgery | Any operative procedure will be included. | Includes all randomized patients, n=51. | Posted | Count of Participants | Participants | From start of therapy through completion of therapy, up to 56 weeks |
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| Secondary | Number of Participants Who Undergo Transfusion | Transfusion will be defined as the provision of red blood cells to correct anemia. | Includes all randomized patients, n=51. | Posted | Count of Participants | Participants | From start of therapy through completion of therapy, up to 56 weeks |
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| Secondary | Number of Patients With Toxicities Related to Hydroxyurea Dosing | Number of patients with toxicities to include: neutropenia (ANC <1000*/µL), reticulocytopenia (ARC <80*10^3/µL and concomitant anemia (hemoglobin <6 g/dL), and thrombocytopenia (platelets <100*10^3/µL). | N=51 randomized patients (n=25 intensive arm and n=26 standard arm). | Posted | Count of Participants | Participants | From start of therapy through completion of therapy, up to 56 weeks |
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| Secondary | Number of Toxicities Related to Hydroxyurea Dosing | Number of toxicities will be reported to include: neutropenia (ANC <1000*/µL), reticulocytopenia (ARC <80*10^3/µL and concomitant anemia (hemoglobin <6 g/dL), and thrombocytopenia (platelets <100*10^3/µL). | N=51 randomized patients (n=25 intensive arm and n=26 standard arm). | Posted | Number | Toxicities | From start of therapy through completion of therapy, up to 56 weeks |
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| Secondary | Change in Pain and Hurt Score | Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score. | Of the N=51 randomized patients (n=25 intensive arm and n=26 standard arm), only 1 patient had The PedsQL ™ Sickle Cell Disease Module data at both baseline and exit visit. | Posted | Mean | Standard Deviation | score on a scale | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Change in Pain Impact Score | Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score. | Of the N=51 randomized patients (n=25 intensive arm and n=26 standard arm), only 1 patient had The PedsQL ™ Sickle Cell Disease Module data at both baseline and exit visit. | Posted | Mean | Standard Deviation | score on a scale | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Change in Pain Management Score | Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score. | Of the N=51 randomized patients (n=25 intensive arm and n=26 standard arm), only 1 patient had The PedsQL ™ Sickle Cell Disease Module data at both baseline and exit visit. | Posted | Mean | Standard Deviation | score on a scale | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Change in Worry I Score | Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score. | Of the N=51 randomized patients (n=25 intensive arm and n=26 standard arm), only 1 patient had The PedsQL ™ Sickle Cell Disease Module data at both baseline and exit visit. | Posted | Mean | Standard Deviation | score on a scale | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Change in Worry II Score | Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score. | Of the N=51 randomized patients (n=25 intensive arm and n=26 standard arm), only 1 patient had The PedsQL ™ Sickle Cell Disease Module data at both baseline and exit visit. | Posted | Mean | Standard Deviation | score on a scale | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Change in Emotions Score | Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score. | Of the N=51 randomized patients (n=25 intensive arm and n=26 standard arm), only 1 patient had The PedsQL ™ Sickle Cell Disease Module data at both baseline and exit visit. | Posted | Mean | Standard Deviation | score on a scale | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Change in Treatment Score | Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score. | Of the N=51 randomized patients (n=25 intensive arm and n=26 standard arm), only 1 patient had The PedsQL ™ Sickle Cell Disease Module data at both baseline and exit visit. | Posted | Mean | Standard Deviation | score on a scale | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Change in Communication I Score | Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score. | Of the N=51 randomized patients (n=25 intensive arm and n=26 standard arm), only 1 patient had The PedsQL ™ Sickle Cell Disease Module data at both baseline and exit visit. | Posted | Mean | Standard Deviation | score on a scale | From baseline at study entry to completion of therapy, up to 56 weeks |
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| Secondary | Change in Communication II Score | Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score. | Of the N=51 randomized patients (n=25 intensive arm and n=26 standard arm), only 1 patient had The PedsQL ™ Sickle Cell Disease Module data at both baseline and exit visit. | Posted | Mean | Standard Deviation | score on a scale | From baseline at study entry to completion of therapy, up to 56 weeks |
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| 1 |
| 26 |
| 3 |
| 26 |
| 2 |
| 26 |
| EG001 | Intensive Dosing - Post Randomization | In the first 8 weeks (± 2 weeks) of this study, participants will receive standard treatment [a fixed dose of 20 (± 2.5) mg/kg/day of hydroxyurea]. After 8 weeks (± 2 weeks) of standard treatment, participants will be randomized (like flipping a coin) to one of two treatment groups. Group 2 (Intensive Dosing) will have their HU dose increased by 5 mg/kg/day every 8 weeks up to a maximum of 35 mg/kg/day. | 0 | 25 | 2 | 25 | 8 | 25 |
| EG002 | All Participants - Pre Randomization | All participants enrolled | 0 | 58 | 1 | 58 | 3 | 58 |
| Immune system disorders,- Other specify | Immune system disorders | CTCAE (4.0) | Systematic Assessment | Fever in pediatric patient |
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| Other (Specify_) | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment | "breath holding spell" |
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| Neutropenia | Immune system disorders | CTCAE (4.0) | Systematic Assessment |
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| Infections and infestations - Other, specify | Infections and infestations | CTCAE (4.0) | Systematic Assessment | Norovirus/rotovirus diarrhea |
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| Sepsis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
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| Surgical and medical procedures - Other specify | Surgical and medical procedures | CTCAE (4.0) | Systematic Assessment | Removal of foreign object |
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| Platelet count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
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Not provided
Not provided
Not provided
| D006425 |
| Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| Unknown reason |
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| Not interested in HU |
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| Poor clinic visit compliance |
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| Not interested in research |
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| Logistics - travel distance to site, frequency of appointments |
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| Thrombocytopenia |
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| Anemia |
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| Thrombocytopenia |
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| Anemia |
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