Anemia, Sickle Cell
Conditions
Keywords
Sickle Cell Anemia, Hydroxyurea
Brief summary
Sickle cell anemia (SCA) is an inherited blood disorder that can cause organ damage. The BABY HUG study is evaluating the use of the medication hydroxyurea at preventing organ damage in children with SCA. The purpose of this follow-up study is to evaluate the long-term effects of hydroxyurea in children who have participated in the BABY HUG study.
Detailed description
SCA is an inherited blood disorder in which the body makes sickle-shaped red blood cells that contain abnormal hemoglobin. The sickled cells block blood flow in the vessels that lead to limbs and organs. This can cause pain, serious infections, and organ damage. The BABY HUG study (NCT00006400) is examining whether the medication hydroxyurea can prevent organ damage, especially in the spleen and kidneys, in children with SCA. This study is a follow-up study to the BABY HUG study and will enroll children who have participated in the BABY HUG study. The purpose of this study is to examine the long-term effects of using hydroxyurea as a treatment for SCA, including both the risks and benefits. Study researchers will also investigate the optimal age to begin treatment with hydroxyurea in children with SCA. This study will enroll children between 2 and 7 years old who participated in the BABY HUG study. Hydroxyurea will not be provided to participants as part of this study, but participants may receive the medication from their own doctors. Parents of participants can choose for their child to participate in this study in one of two ways-by enrolling in either a passive follow-up group or an active follow-up group. For participants in the passive follow-up group, study researchers will review participants' medical records every 6 months, in addition to reviewing brain ultrasound tests and computed tomography (CT) or magnetic resonance imaging (MRI) scans, if completed. Participants will have a blood and urine collection at baseline and Year 4 (or at the end of the study, whichever comes first). Participants in the active follow-up group will take part in the same study procedures as participants in the passive follow-up group. In addition, at Year 2, participants in this group will undergo an additional blood and urine collection, a scanning procedure to obtain images of the liver and spleen, a kidney test, neuropsychological testing, and an ultrasound imaging test to evaluate liver and spleen size.
Interventions
DRUGHydroxyurea
Parents and child's doctor may plan to use or not to use hydroxyurea.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
2 Years to 7 Years
Healthy volunteers
No
Inclusion criteria
* All children who completed at least 18 months of follow-up visits in the initial BABY HUG study * Children from the initial BABY HUG study who are on a chronic transfusion program or who are recipients of a bone marrow transplant
Exclusion criteria
* Any child who was not enrolled in the initial BABY HUG study for at least 18 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Qualitative Spleen Function From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | 48 Months from the date of randomization | The change in splenic function from the randomized control trial baseline measurement was one of the primary outcomes. The change in splenic function (worse vs not-worse) was compared between the randomized treatment groups (hydroxyurea vs placebo). The change in splenic function from baseline to 48 months was defined as worse if it changed from normal to decreased or absent, or decreased to absent; and not worse if it changed from decreased to decreased, normal to normal, decreased to normal, absent to absent, or absent to decreased. |
| Change in Qualitative Spleen Function From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit | 48 Months from the date of randomization | The change in splenic function from the randomized control trial baseline measurement was one of the primary outcomes.The change in splenic function (worse vs not-worse) was compared between children who were known to be on hydroxyurea vs. off hydroxyurea at the time of the visit. The change in splenic function from baseline to 48 months was defined as worse if it changed from normal to decreased or absent, or decreased to absent; and not worse if it changed from decreased to decreased, normal to normal, decreased to normal, absent to absent, or absent to decreased. |
| Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | 48 Months from the date of randomization | The change in the percentage of pitted cell from randomized control trial baseline measurement was one of the primary outcomes. The change in the percentage of pitted cell was compared between the randomized treatment groups (hydroxyurea vs placebo). |
| Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit | 48 Months from the date of randomization | The change in the percentage of pitted cell from the randomized control trial baseline measurement was one of the primary outcomes. The change in the percentage of pitted cell was compared between children who were known to be on hydroxyurea vs. off hydroxyurea at the time of the visit. |
| Change in Howell-Jolly Bodies (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | 48 Months from the date of randomization | The change in Howell-Jolly Bodies from randomized control trial baseline measurement was one of the primary outcomes. The change in Howell-Jolly Bodies was compared between the randomized treatment groups (hydroxyurea vs placebo). |
| Change in Howell-Jolly Bodies (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit | 48 Months from the date of randomization | The change in Howell-Jolly Bodies from the randomized control trial baseline measurement was one of the primary outcomes. The change in Howell-Jolly Bodies was compared between children who were known to be on hydroxyurea vs. off hydroxyurea at the time of the visit. |
| Change in Howell-Jolly Bodies From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit | 72 Months from the date of randomization | The change in Howell-Jolly Bodies (HJB) from the randomized control trial baseline measurement was one of the primary outcomes. The change in Howell-Jolly Bodies was compared between children who were known to be on hydroxyurea vs. off hydroxyurea at the time of the visit. |
Countries
United States
Participant flow
Recruitment details
Subjects that were eligible for enrollment included all children who have completed at least 18 months of the BABY HUG Treatment Study.
Pre-assignment details
Parents and the participants' health care providers, who had not yet been informed of the BABY HUG randomized treatment, selected open label hydroxyurea (HU) treatment or standard care (SC).
Participants by arm
| Arm | Count |
|---|---|
| Active An active follow-up involved the performance of many of the laboratory tests and procedures done during BABY HUG clinical trials study. These included, but not limited to, serial laboratory parameters that were not part of routine clinical care such as Hgb F levels, pitted cell count, Howell-Jolly Body determination, a liver-spleen scan, DTPA GFR measurement, creatinine clearance, Cystatin C, urine concentrating ability, transcranial Doppler, and neuropsychological testing. Patients could be on or off hydroxyurea at the start of Follow-Up Study I, and could change treatment during the study. | 127 |
| Passive A passive follow-up involved the abstraction of clinical data from the medical record. Results of physical examinations and laboratory tests performed as part of routine clinical care were recorded. Patients could be on or off hydroxyurea at the start of Follow-Up Study I, and could change treatment during the study. | 36 |
| Total | 163 |
Baseline characteristics
| Characteristic | Passive | Active | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 36 Participants | 127 Participants | 163 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 4.65 Years STANDARD_DEVIATION 1.25 | 4.41 Years STANDARD_DEVIATION 1.12 | 4.46 Years STANDARD_DEVIATION 1.15 |
| Region of Enrollment United States | 36 participants | 127 participants | 163 participants |
| Sex: Female, Male Female | 25 Participants | 68 Participants | 93 Participants |
| Sex: Female, Male Male | 11 Participants | 59 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 84 | 0 / 79 |
| other Total, other adverse events | 0 / 84 | 0 / 79 |
| serious Total, serious adverse events | 1 / 84 | 1 / 79 |
Outcome results
Primary
Change in Howell-Jolly Bodies From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit
The change in Howell-Jolly Bodies (HJB) from the randomized control trial baseline measurement was one of the primary outcomes. The change in Howell-Jolly Bodies was compared between children who were known to be on hydroxyurea vs. off hydroxyurea at the time of the visit.
Time frame: 72 Months from the date of randomization
Population: All subjects who were known to be on hydroxyurea vs. off hydroxyurea at the 72 month visit, and had 72 month and baseline Howell-Jolly Bodies measurements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Randomized to Hydroxyurea | Change in Howell-Jolly Bodies From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit | 1972.00 Number of HJB per 10⁶ red blood cell |
| Randomized to Placebo | Change in Howell-Jolly Bodies From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit | 1500.50 Number of HJB per 10⁶ red blood cell |
Comparison: Kruskal-Wallis test was used to test if there were a statistically significant difference between the two treatment groups.p-value: 0.11Kruskal-Wallis
Primary
Change in Howell-Jolly Bodies (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit
The change in Howell-Jolly Bodies from the randomized control trial baseline measurement was one of the primary outcomes. The change in Howell-Jolly Bodies was compared between children who were known to be on hydroxyurea vs. off hydroxyurea at the time of the visit.
Time frame: 48 Months from the date of randomization
Population: All subjects who were known to be on hydroxyurea vs. off hydroxyurea at the 48 month visit, and had 48 month and baseline Howell-Jolly Bodies measurements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Randomized to Hydroxyurea | Change in Howell-Jolly Bodies (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit | 1661.00 Number of HJB per 10⁶ red blood cell |
| Randomized to Placebo | Change in Howell-Jolly Bodies (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit | 1510.00 Number of HJB per 10⁶ red blood cell |
Comparison: Kruskal-Wallis test was used to test if there were a statistically significant difference between the two treatment groups.p-value: 0.4Kruskal-Wallis
Primary
Change in Howell-Jolly Bodies (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo
The change in Howell-Jolly Bodies from randomized control trial baseline measurement was one of the primary outcomes. The change in Howell-Jolly Bodies was compared between the randomized treatment groups (hydroxyurea vs placebo).
Time frame: 48 Months from the date of randomization
Population: All subjects who had 48 month and baseline Howell-Jolly Bodies measurements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Randomized to Hydroxyurea | Change in Howell-Jolly Bodies (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | 1626.25 Number of HJB per 10⁶ red blood cell |
| Randomized to Placebo | Change in Howell-Jolly Bodies (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | 1553.00 Number of HJB per 10⁶ red blood cell |
Comparison: Kruskal-Wallis test was used to test if there were a statistically significant difference between the two treatment groups.p-value: 0.85Kruskal-Wallis
Primary
Change in Howell-Jolly Bodies (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo
The change in Howell-Jolly Bodies from randomized control trial baseline measurement was one of the primary outcomes. The change in Howell-Jolly Bodies was compared between the randomized treatment groups (hydroxyurea vs placebo).
Time frame: 72 Months from the date of randomization
Population: All subjects who had 72 month and baseline Howell-Jolly Bodies measurements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Randomized to Hydroxyurea | Change in Howell-Jolly Bodies (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | 1847.50 Number of HJB per 10⁶ red blood cell |
| Randomized to Placebo | Change in Howell-Jolly Bodies (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | 1906.50 Number of HJB per 10⁶ red blood cell |
Comparison: Kruskal-Wallis test was used to test if there were a statistically significant difference between the two treatment groups.p-value: 0.95Kruskal-Wallis
Primary
Change in Qualitative Spleen Function From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit
The change in splenic function from the randomized control trial baseline measurement was one of the primary outcomes.The change in splenic function (worse vs not-worse) was compared between children who were known to be on hydroxyurea vs. off hydroxyurea at the time of the visit. The change in splenic function from baseline to 48 months was defined as worse if it changed from normal to decreased or absent, or decreased to absent; and not worse if it changed from decreased to decreased, normal to normal, decreased to normal, absent to absent, or absent to decreased.
Time frame: 48 Months from the date of randomization
Population: All subjects who were known to be on hydroxyurea vs. off hydroxyurea at the 48 month visit, and had 48 month and baseline spleen function measurement.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized to Hydroxyurea | Change in Qualitative Spleen Function From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit | Splenic function - worse from baseline | 26 Participants |
| Randomized to Hydroxyurea | Change in Qualitative Spleen Function From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit | Splenic function - not worse from baseline | 62 Participants |
| Randomized to Placebo | Change in Qualitative Spleen Function From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit | Splenic function - worse from baseline | 5 Participants |
| Randomized to Placebo | Change in Qualitative Spleen Function From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit | Splenic function - not worse from baseline | 13 Participants |
Comparison: The primary analysis compared the frequency of worsening spleen function (from normal to decreased or absent, or from decreased to absent).p-value: >0.99Fisher Exact
Primary
Change in Qualitative Spleen Function From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo
The change in splenic function from the randomized control trial baseline measurement was one of the primary outcomes. The change in splenic function (worse vs not-worse) was compared between the randomized treatment groups (hydroxyurea vs placebo). The change in splenic function from baseline to 48 months was defined as worse if it changed from normal to decreased or absent, or decreased to absent; and not worse if it changed from decreased to decreased, normal to normal, decreased to normal, absent to absent, or absent to decreased.
Time frame: 48 Months from the date of randomization
Population: All subjects who had 48 month and baseline spleen function measurement.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized to Hydroxyurea | Change in Qualitative Spleen Function From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | Splenic function - worse from baseline | 16 Participants |
| Randomized to Hydroxyurea | Change in Qualitative Spleen Function From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | Splenic function - not worse from baseline | 44 Participants |
| Randomized to Placebo | Change in Qualitative Spleen Function From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | Splenic function - worse from baseline | 15 Participants |
| Randomized to Placebo | Change in Qualitative Spleen Function From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | Splenic function - not worse from baseline | 34 Participants |
Comparison: The primary analysis compared the frequency of worsening spleen function (from normal to decreased or absent, or from decreased to absent).p-value: 0.67Fisher Exact
Primary
Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit
The change in the percentage of pitted cell from the randomized control trial baseline measurement was one of the primary outcomes. The change in the percentage of pitted cell was compared between children who were known to be on hydroxyurea vs. off hydroxyurea at the time of the visit.
Time frame: 72 Months from the date of randomization
Population: All subjects who were known to be on hydroxyurea vs. off hydroxyurea at the 72 month visit, and had 72 month and baseline pitted cell measurements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Randomized to Hydroxyurea | Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit | -1.30 Percentage of pitted cell |
| Randomized to Placebo | Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit | -1.70 Percentage of pitted cell |
Comparison: Kruskal-Wallis test was used to test if there were a statistically significant difference between the two treatment groups.p-value: 0.11Kruskal-Wallis
Primary
Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit
The change in the percentage of pitted cell from the randomized control trial baseline measurement was one of the primary outcomes. The change in the percentage of pitted cell was compared between children who were known to be on hydroxyurea vs. off hydroxyurea at the time of the visit.
Time frame: 48 Months from the date of randomization
Population: All subjects who were known to be on hydroxyurea vs. off hydroxyurea at the 48 month visit, and had 48 month and baseline pitted cell measurements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Randomized to Hydroxyurea | Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit | -1.40 Percentage of pitted cell |
| Randomized to Placebo | Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit | -0.60 Percentage of pitted cell |
Comparison: Kruskal-Wallis test was used to test if there were a statistically significant difference between the two treatment groups.p-value: 0.8Kruskal-Wallis
Primary
Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo
The change in the percentage of pitted cell from randomized control trial baseline measurement was one of the primary outcomes. The change in the percentage of pitted cell was compared between the randomized treatment groups (hydroxyurea vs placebo).
Time frame: 72 Months from the date of randomization
Population: All subjects who had 72 month and baseline pitted cell measurements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Randomized to Hydroxyurea | Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | -1.55 Percentage of pitted cell |
| Randomized to Placebo | Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | -1.40 Percentage of pitted cell |
Comparison: Kruskal-Wallis test was used to test if there were a statistically significant difference between the two treatment groups.p-value: 0.78Kruskal-Wallis
Primary
Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo
The change in the percentage of pitted cell from randomized control trial baseline measurement was one of the primary outcomes. The change in the percentage of pitted cell was compared between the randomized treatment groups (hydroxyurea vs placebo).
Time frame: 48 Months from the date of randomization
Population: All subjects who had 48 month and baseline pitted cell measurements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Randomized to Hydroxyurea | Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | -1.70 Percentage of pitted cell |
| Randomized to Placebo | Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | -1.00 Percentage of pitted cell |
Comparison: Kruskal-Wallis test was used to test if there were a statistically significant difference between the two treatment groups.p-value: 0.61Kruskal-Wallis