Sickle Cell Anemia
Conditions
Brief summary
The BABY HUG Treatment Study was designed to see if treatment with the drug hydroxyurea (also called HU) in children with sickle cell disease could prevent organ damage, especially in the spleen and kidneys. There was also a chance that treatment could prevent painful crises, lung disease, stroke, and blood infection.
Detailed description
The current observational trial, Follow-Up Study ((FUS) II includes enhanced neuropsychological, brain, cardiac, and pulmonary evaluations for this very well characterized cohort of subjects. Measures of spleen and renal function and markers of DNA damage will continue to be collected. Assessment of other target organs in sickle cell disease including pulmonary and cardiac function will be performed in addition to evaluation of developmental aspects of sickle cell disease (SCD) and potential HU toxicity.
Interventions
DRUGHydroxyurea
Parents and child's doctor may plan to use or not to use hydroxyurea.
Sponsors
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
24 Months to 18 Years
Healthy volunteers
No
Inclusion criteria
* All subjects enrolled in the BABY HUG Follow-Up I Study who participated for at least 24 months are eligible for the Follow-Up Study II
Exclusion criteria
* Subjects that have received a Stem Cell Transplant are not eligible for enrollment
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 | baseline and when child turned 10 years old | 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 (before treatment initiation) to age 10 years (a visit when child turned 10 years old) 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 | baseline and when child turned 10 years old | 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 (before treatment initiation) to age 10 years (a visit when child turned 10 years old) 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 | Baseline and End of follow-up II study (up to 13 years from randomization date) | 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 | Baseline and End of follow-up II study (up to 13 years from randomization date) | 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 Body (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | Baseline and End of follow-up II study (up to 13 years from randomization date) | The change in Howell Jolly Body from the randomized control trial baseline measurement was one of the primary outcomes. The change in Howell Jolly Body was compared between the randomized treatment groups (hydroxyurea vs placebo). |
| Change in Howell Jolly Body (HJB) Count From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea | Baseline and End of follow-up II study (up to 13 years from randomization date) | The change in Howell Jolly Body count 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
Participants by arm
| Arm | Count |
|---|---|
| Active Blood and urine specimens, and questionnaires related to the child's health status.
* Liver Spleen Scan
* Abdominal Ultrasound
* Brain magnetic resonance imaging (MRI) / magnetic resonance angiography (MRA)
* Cardiac Echocardiogram/Pulmonary Function Testing
* Transcranial Doppler
* Neuropsychology Testing (Vineland, Wechsler Intelligence Scale for Children (WISC-IV), Connor Continuous Performance Test 2nd Edition (CPT II) and Pediatric Quality of Life Inventory(PedsQOL))
Patients could be on or off hydroxyurea at the start of Follow-Up Study II, and could change treatment during the study. | 130 |
| Passive Information from usual clinical care of sickle cell disease. We will collect information from routine tests ordered by the child's clinical sickle cell doctors.
Patients could be on or off hydroxyurea at the start of Follow-Up Study II, and could change treatment during the study. | 20 |
| Total | 150 |
Baseline characteristics
| Characteristic | Active | Passive | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 130 Participants | 20 Participants | 150 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 | 8.16 Years STANDARD_DEVIATION 1.13 | 8.06 Years STANDARD_DEVIATION 1.26 | 8.15 Years STANDARD_DEVIATION 1.14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 125 Participants | 19 Participants | 144 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 122 Participants | 18 Participants | 140 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 130 participants | 20 participants | 150 participants |
| Sex: Female, Male Female | 70 Participants | 14 Participants | 84 Participants |
| Sex: Female, Male Male | 60 Participants | 6 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 77 | 0 / 73 |
| other Total, other adverse events | 0 / 77 | 0 / 73 |
| serious Total, serious adverse events | 24 / 77 | 31 / 73 |
Outcome results
Primary
Change in Howell Jolly Body (HJB) Count From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea
The change in Howell Jolly Body count 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: Baseline and End of follow-up II study (up to 13 years from randomization date)
Population: All subjects who were known to be on hydroxyurea vs. off hydroxyurea at the end of study visit, and had end of study and baseline Howell Jolly Body count measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Randomized to Hydroxyurea | Change in Howell Jolly Body (HJB) Count From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea | 2645.43 Number of HJB per 10⁶ red blood cell |
| Randomized to Placebo | Change in Howell Jolly Body (HJB) Count From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea | 1833.73 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: 0.04Kruskal-Wallis
Primary
Change in Howell Jolly Body (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo
The change in Howell Jolly Body from the randomized control trial baseline measurement was one of the primary outcomes. The change in Howell Jolly Body was compared between the randomized treatment groups (hydroxyurea vs placebo).
Time frame: Baseline and End of follow-up II study (up to 13 years from randomization date)
Population: All subjects who had end of follow-up study II and baseline howell jolly body count measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Randomized to Hydroxyurea | Change in Howell Jolly Body (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | 2719.88 Number of HJB per 10⁶ red blood cell |
| Randomized to Placebo | Change in Howell Jolly Body (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | 2248.55 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: 0.31Kruskal-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 (before treatment initiation) to age 10 years (a visit when child turned 10 years old) 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: baseline and when child turned 10 years old
Population: All subjects who were known to be on hydroxyurea vs. off hydroxyurea at age 10 years, and had age 10 years 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 | 43 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 | 45 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 | 9 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 | 8 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: 0.8Fisher 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 (before treatment initiation) to age 10 years (a visit when child turned 10 years old) 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: baseline and when child turned 10 years old
Population: All subjects who had age 10 years 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 - not worse from baseline | 32 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 | 26 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 | 28 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 | 22 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: 0.33Fisher 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: Baseline and End of follow-up II study (up to 13 years from randomization date)
Population: All subjects who were known to be on hydroxyurea vs. off hydroxyurea at the end of study visit, and had end of study and baseline pitted cell count measurement.
| 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 | -1.80 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 | -0.80 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: 0.28Kruskal-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: Baseline and End of follow-up II study (up to 13 years from randomization date)
Population: All subjects who had end of study and baseline pitted cell measurement.
| 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 | -1.60 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 | -1.75 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: 0.87Kruskal-Wallis