Long-Term Effects of Hydroxyurea in Children With Sickle Cell Anemia (The BABY HUG Follow-up Study)

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00890396
• Collaborator: (none)
• Enrollment: 163
• Locations: 14
• Duration (Months): 39
• Patients Per Site: 11.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Anemia, Sickle Cell	Drug: Hydroxyurea

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 163 participants
• Observational Model: Cohort
• Time Perspective: Other
• Official Title: Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG) Follow-up Study
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Follow-up 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, diethylenetriaminepentaacetic acid (DTPA) glomerular filtration rate (GFR) measurement, creatinine clearance, Cystatin C, urine concentrating ability, transcranial Doppler, and neuropsychological testing.	Drug: Hydroxyurea; Parents and child's doctor may plan to use or not to use hydroxyurea.
Passive Follow-up 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.	Drug: Hydroxyurea; Parents and child's doctor may plan to use or not to use hydroxyurea.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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).

4. Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo [72 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).

5. 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.

6. Change in the Percentage of Pitted Cell 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 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.

7. 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).

8. Change in Howell-Jolly Bodies (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo [72 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).

9. 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.

10. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 7 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Children's National Medical Center	Washington	District of Columbia	United States	20010
3	Howard University College of Medicine	Washington	District of Columbia	United States	20060
4	University of Miami School of Medicine	Miami	Florida	United States	33136
5	Emory University School of Medicine	Atlanta	Georgia	United States	30342
6	Johns Hopkins University School of Medicine	Baltimore	Maryland	United States	21205
7	Children's Hospital of Michigan/Wayne State University	Detroit	Michigan	United States	48201
8	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
9	Downstate Medical Center	Brooklyn	New York	United States	11203
10	Duke University Medical Center	Durham	North Carolina	United States	27710
11	Drexel University	Philadelphia	Pennsylvania	United States	19134
12	Medical University of South Carolina	Charleston	South Carolina	United States	29425
13	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
14	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas	United States	75390

Sponsors and Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Susan Assmann, PhD, New England Research Institutes, Watertown, MA

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan: BABY HUG Randomized Control Trial - Aug 9, 2009
• Informed Consent Form: BABY HUG Randomized Control Trial - Oct 16, 2006
• Informed Consent Form: BABY HUG Follow-up Study I - Nov 10, 2006
• Study Protocol and Statistical Analysis Plan: BABY HUG Follow-up Study I - Jan 4, 2010

More Information

Publications

None provided.

• Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
• ClinicalTrials.gov Identifier: NCT00890396
• Other Study ID Numbers: 647; N01 HB07160
• First Posted: Apr 29, 2009
• Last Update Posted: Aug 20, 2020
• Last Verified: Jul 1, 2009

• Keywords provided by National Heart, Lung, and Blood Institute (NHLBI): Sickle Cell Anemia; Hydroxyurea
• Additional relevant MeSH terms: Anemia; Anemia, Sickle Cell; Hydroxyurea

Study Results

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 Detail	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).

Arm/Group Title	Active	Passive
Arm/Group Description	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, diethylenetriaminepentaacetic acid (DTPA) glomerular filtration rate (GFR) measurement, creatinine clearance, Cystatin C, urine concentrating ability, transcranial Doppler, and neuropsychological testing.	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.
Period Title: Overall Study
STARTED	127	36
COMPLETED	122	34
NOT COMPLETED	5	2

Baseline Characteristics

Arm/Group Title	Active	Passive	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	127	36	163
Age (Count of Participants)
<=18 years	127 100%	36 100%	163 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	4.41 (1.12)	4.65 (1.25)	4.46 (1.15)
Sex: Female, Male (Count of Participants)
Female	68 53.5%	25 69.4%	93 57.1%
Male	59 46.5%	11 30.6%	70 42.9%
Region of Enrollment (participants) [Number]
United States	127 100%	36 100%	163 100%

Outcome Measures

1. Primary Outcome

Title	Change in Qualitative Spleen Function From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo
Description	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

Outcome Measure Data

Analysis Population Description

All subjects who had 48 month and baseline spleen function measurement.

Arm/Group Title	Randomized to Hydroxyurea	Randomized to Placebo
Arm/Group Description	Subjects randomized to Hydroxyurea in the randomized phase III clinical trial.	Subjects randomized to Placebo in the randomized phase III clinical trial.
Measure Participants	60	49
Splenic function - worse from baseline	16 12.6%	15 41.7%
Splenic function - not worse from baseline	44 34.6%	34 94.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Randomized to Hydroxyurea, Randomized to Placebo
	Comments	The primary analysis compared the frequency of worsening spleen function (from normal to decreased or absent, or from decreased to absent).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.67
	Comments
	Method	Fisher Exact
	Comments

2. Primary Outcome

Title	Change in Qualitative Spleen Function From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	On Hydroxyurea at the Time of Visit	Off Hydroxyurea at the Time of Visit
Arm/Group Description	Subjects who were on hydroxyurea at the time of study visit	Subjects who were off hydroxyurea at the time of study visit
Measure Participants	88	18
Splenic function - worse from baseline	26 20.5%	5 13.9%
Splenic function - not worse from baseline	62 48.8%	13 36.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Randomized to Hydroxyurea, Randomized to Placebo
	Comments	The primary analysis compared the frequency of worsening spleen function (from normal to decreased or absent, or from decreased to absent).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.99
	Comments
	Method	Fisher Exact
	Comments

3. Primary Outcome

Title	Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo
Description	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

Outcome Measure Data

Analysis Population Description

All subjects who had 48 month and baseline pitted cell measurements.

Arm/Group Title	Randomized to Hydroxyurea	Randomized to Placebo
Arm/Group Description	Subjects randomized to Hydroxyurea in the randomized phase III clinical trial.	Subjects randomized to Placebo in the randomized phase III clinical trial.
Measure Participants	59	49
Median (Inter-Quartile Range) [Percentage of pitted cell]	-1.70	-1.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Randomized to Hydroxyurea, Randomized to Placebo
	Comments	Kruskal-Wallis test was used to test if there were a statistically significant difference between the two treatment groups.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.61
	Comments
	Method	Kruskal-Wallis
	Comments

4. Primary Outcome

Title	Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo
Description	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

Outcome Measure Data

Analysis Population Description

All subjects who had 72 month and baseline pitted cell measurements.

Arm/Group Title	Randomized to Hydroxyurea	Randomized to Placebo
Arm/Group Description	Subjects randomized to Hydroxyurea in the randomized phase III clinical trial.	Subjects randomized to placebo in the randomized phase III clinical trial.
Measure Participants	70	64
Median (Inter-Quartile Range) [Percentage of pitted cell]	-1.55	-1.40

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Randomized to Hydroxyurea, Randomized to Placebo
	Comments	Kruskal-Wallis test was used to test if there were a statistically significant difference between the two treatment groups.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.78
	Comments
	Method	Kruskal-Wallis
	Comments

5. Primary Outcome

Title	Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	On Hydroxyurea at the Time of Visit	Off Hydroxyurea at the Time of Visit
Arm/Group Description	Subjects who were on hydroxyurea at the time of study visit	Subjects who were off hydroxyurea at the time of study visit
Measure Participants	91	15
Median (Inter-Quartile Range) [Percentage of pitted cell]	-1.40	-0.60

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Randomized to Hydroxyurea, Randomized to Placebo
	Comments	Kruskal-Wallis test was used to test if there were a statistically significant difference between the two treatment groups.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.80
	Comments
	Method	Kruskal-Wallis
	Comments

6. Primary Outcome

Title	Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	On Hydroxyurea at the Time of Visit	Off Hydroxyurea at the Time of Visit
Arm/Group Description	Subjects who were on hydroxyurea at the time of study visit	Subjects who were off hydroxyurea at the time of study visit
Measure Participants	104	27
Median (Inter-Quartile Range) [Percentage of pitted cell]	-1.30	-1.70

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Randomized to Hydroxyurea, Randomized to Placebo
	Comments	Kruskal-Wallis test was used to test if there were a statistically significant difference between the two treatment groups.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	Kruskal-Wallis
	Comments

7. Primary Outcome

Title	Change in Howell-Jolly Bodies (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo
Description	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

Outcome Measure Data

Analysis Population Description

All subjects who had 48 month and baseline Howell-Jolly Bodies measurements.

Arm/Group Title	Randomized to Hydroxyurea	Randomized to Placebo
Arm/Group Description	Subjects randomized to Hydroxyurea in the randomized phase III clinical trial.	Subjects randomized to Placebo in the randomized phase III clinical trial.
Measure Participants	52	40
Median (Inter-Quartile Range) [Number of HJB per 10⁶ red blood cell]	1626.25	1553.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Randomized to Hydroxyurea, Randomized to Placebo
	Comments	Kruskal-Wallis test was used to test if there were a statistically significant difference between the two treatment groups.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.85
	Comments
	Method	Kruskal-Wallis
	Comments

8. Primary Outcome

Title	Change in Howell-Jolly Bodies (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo
Description	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

Outcome Measure Data

Analysis Population Description

All subjects who had 72 month and baseline Howell-Jolly Bodies measurements.

Arm/Group Title	Randomized to Hydroxyurea	Randomized to Placebo
Arm/Group Description	Subjects randomized to Hydroxyurea in the randomized phase III clinical trial.	Subjects randomized to Placebo in the randomized phase III clinical trial.
Measure Participants	22	20
Median (Inter-Quartile Range) [Number of HJB per 10⁶ red blood cell]	1847.50	1906.50

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Randomized to Hydroxyurea, Randomized to Placebo
	Comments	Kruskal-Wallis test was used to test if there were a statistically significant difference between the two treatment groups.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.95
	Comments
	Method	Kruskal-Wallis
	Comments

9. Primary Outcome

Title	Change in Howell-Jolly Bodies (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	On Hydroxyurea at the Time of Visit	Off Hydroxyurea at the Time of Visit
Arm/Group Description	Subjects who were on hydroxyurea at the time of study visit	Subjects who were off hydroxyurea at the time of study visit
Measure Participants	79	11
Median (Inter-Quartile Range) [Number of HJB per 10⁶ red blood cell]	1661.00	1510.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Randomized to Hydroxyurea, Randomized to Placebo
	Comments	Kruskal-Wallis test was used to test if there were a statistically significant difference between the two treatment groups.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.40
	Comments
	Method	Kruskal-Wallis
	Comments

10. Primary Outcome

Title	Change in Howell-Jolly Bodies From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	On Hydroxyurea at the Time of Visit	Off Hydroxyurea at the Time of Visit
Arm/Group Description	Subjects who were on hydroxyurea at the time of study visit	Subjects who were off hydroxyurea at the time of study visit
Measure Participants	29	12
Median (Inter-Quartile Range) [Number of HJB per 10⁶ red blood cell]	1972.00	1500.50

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Randomized to Hydroxyurea, Randomized to Placebo
	Comments	Kruskal-Wallis test was used to test if there were a statistically significant difference between the two treatment groups.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	Kruskal-Wallis
	Comments

Adverse Events

Time Frame	The date of consent to follow-up study I (FUS-I) through end of FUS-I, up to 2 years
Adverse Event Reporting Description	Serious adverse event (SAE) were Death, Life-threatening event, Prolonged hospitalization (greater than 7 days), Splenic sequestration crisis, Stroke / transient ischemic attack (TIA), Acute chest syndrome, or ICU admissions, and occurred during the first 5 days following performance of an active assessment study.
Arm/Group Title	Randomized to Hydroxyurea		Randomized to Placebo
Arm/Group Description	Subjects randomized to Hydroxyurea in the randomized phase III clinical trial.		Subjects randomized to Placebo in the randomized phase III clinical trial.
All Cause Mortality
	Randomized to Hydroxyurea		Randomized to Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/84 (0%)		0/79 (0%)
Serious Adverse Events
	Randomized to Hydroxyurea		Randomized to Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/84 (1.2%)		1/79 (1.3%)
Respiratory, thoracic and mediastinal disorders
Acute chest syndrome	1/84 (1.2%)	1	1/79 (1.3%)	1
Other (Not Including Serious) Adverse Events
	Randomized to Hydroxyurea		Randomized to Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/84 (0%)		0/79 (0%)

Limitations/Caveats

Most children used hydroxyurea (HU) for at least part of the FUS-I observation period. This may dilute any effect of randomized group. Most children were on HU at the specified time points, which reduces power to compare on/off HU.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.