Trial Outcomes & Findings for Stroke With Transfusions Changing to Hydroxyurea (NCT NCT00122980)
NCT ID: NCT00122980
Last Updated: 2013-01-18
Results Overview
Secondary stroke is the first component of the composite primary endpoint and considers the number of participants with recurrent secondary stroke events during 30 months of treatment. Stroke was defined as any clinical event with brain injury due to vascular disease. All neurological events underwent formal stroke adjudication.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
134 participants
Primary outcome timeframe
Because the study was terminated early, time frame is from beginning of treatment until end of treatment (up to 30 Months)
Results posted on
2013-01-18
Participant Flow
Phase III First Patient In: 31-October-2006; Last Patient Last Visit: 15-December-2010; 25 medical clinics in the United States of America.
Participant qualification was initially evaluated by medical chart review and interview. Subsequent to subject consent, subjects were further screened to confirm eligibility. Screening included, in part, expert verification of initial stroke and of liver biopsy results prior to randomization.
Participant milestones
| Measure |
Hydroxyurea/Phlebotomy
1: The Hydroxyurea/Phlebotomy group includes participants randomized to Alternative Treatment. Participants commenced hydroxyurea treatment at 20 mg/kg/day with step-wise escalation to maximum tolerated dose (MTD) defined by mild myelosuppression (absolute neutrophil count 2-4 x 10\^9/L). Transfusions continued for 4-9 months during an overlap phase using a modified schedule to protect against recurrent stroke during hydroxyurea dose escalation. Once MTD was reached and transfusions were discontinued, phlebotomy commenced with a target of 10 mL/kg (maximum volume 500mL) blood removed monthly to reduce iron burden. Lower phlebotomy volumes (5 mL/kg) were recommended if participants were excessively anemic (hemoglobin concentration 7.0-7.9 gm/dL); phlebotomy was not performed if the hemoglobin level was \<7.0 gm/dL. The total duration of study treatment was 30 months after randomization, with a final study visit scheduled 6-months after discontinuation of study treatments.
|
Transfusion/Chelation
2: The Transfusion/Chelation group includes participants randomized to Standard Treatment. Participants continued to receive monthly blood transfusions designed to maintain ≤30% HbS, with local discretion regarding type of transfusion (e.g., simple or erythrocytapheresis). These participants also received daily iron chelation typically with deferasirox (Exjade®). Children already on chelation initially maintained their current dose, while those starting deferasirox received 20 mg/kg/day, with dose escalation in both groups as indicated and tolerated.
|
|---|---|---|
|
Overall Study
STARTED
|
67
|
66
|
|
Overall Study
COMPLETED
|
24
|
26
|
|
Overall Study
NOT COMPLETED
|
43
|
40
|
Reasons for withdrawal
| Measure |
Hydroxyurea/Phlebotomy
1: The Hydroxyurea/Phlebotomy group includes participants randomized to Alternative Treatment. Participants commenced hydroxyurea treatment at 20 mg/kg/day with step-wise escalation to maximum tolerated dose (MTD) defined by mild myelosuppression (absolute neutrophil count 2-4 x 10\^9/L). Transfusions continued for 4-9 months during an overlap phase using a modified schedule to protect against recurrent stroke during hydroxyurea dose escalation. Once MTD was reached and transfusions were discontinued, phlebotomy commenced with a target of 10 mL/kg (maximum volume 500mL) blood removed monthly to reduce iron burden. Lower phlebotomy volumes (5 mL/kg) were recommended if participants were excessively anemic (hemoglobin concentration 7.0-7.9 gm/dL); phlebotomy was not performed if the hemoglobin level was \<7.0 gm/dL. The total duration of study treatment was 30 months after randomization, with a final study visit scheduled 6-months after discontinuation of study treatments.
|
Transfusion/Chelation
2: The Transfusion/Chelation group includes participants randomized to Standard Treatment. Participants continued to receive monthly blood transfusions designed to maintain ≤30% HbS, with local discretion regarding type of transfusion (e.g., simple or erythrocytapheresis). These participants also received daily iron chelation typically with deferasirox (Exjade®). Children already on chelation initially maintained their current dose, while those starting deferasirox received 20 mg/kg/day, with dose escalation in both groups as indicated and tolerated.
|
|---|---|---|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Physician Decision
|
2
|
0
|
|
Overall Study
Protocol Violation
|
5
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
3
|
|
Overall Study
Adjudicated stroke (study endpoint)
|
7
|
0
|
|
Overall Study
Study termination
|
27
|
35
|
Baseline Characteristics
Stroke With Transfusions Changing to Hydroxyurea
Baseline characteristics by cohort
| Measure |
Hydroxyurea/Phlebotomy
n=67 Participants
1: The Hydroxyurea/Phlebotomy group includes participants randomized to Alternative Treatment. Participants commenced hydroxyurea treatment at 20 mg/kg/day with step-wise escalation to maximum tolerated dose (MTD) defined by mild myelosuppression (absolute neutrophil count 2-4 x 10\^9/L). Transfusions continued for 4-9 months during an overlap phase using a modified schedule to protect against recurrent stroke during hydroxyurea dose escalation. Once MTD was reached and transfusions were discontinued, phlebotomy commenced with a target of 10 mL/kg (maximum volume 500mL) blood removed monthly to reduce iron burden. Lower phlebotomy volumes (5 mL/kg) were recommended if participants were excessively anemic (hemoglobin concentration 7.0-7.9 gm/dL); phlebotomy was not performed if the hemoglobin level was \<7.0 gm/dL. The total duration of study treatment was 30 months after randomization, with a final study visit scheduled 6-months after discontinuation of study treatments.
|
Transfusion/Chelation
n=66 Participants
2: The Transfusion/Chelation group includes participants randomized to Standard Treatment. Participants continued to receive monthly blood transfusions designed to maintain ≤30% HbS, with local discretion regarding type of transfusion (e.g., simple or erythrocytapheresis). These participants also received daily iron chelation typically with deferasirox (Exjade®). Children already on chelation initially maintained their current dose, while those starting deferasirox received 20 mg/kg/day, with dose escalation in both groups as indicated and tolerated.
|
Total
n=133 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
60 Participants
n=5 Participants
|
60 Participants
n=7 Participants
|
120 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age Continuous
|
13.0 years
STANDARD_DEVIATION 4.05 • n=5 Participants
|
13.3 years
STANDARD_DEVIATION 3.76 • n=7 Participants
|
13.1 years
STANDARD_DEVIATION 3.89 • n=5 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
72 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
63 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
127 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
62 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
126 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
67 participants
n=5 Participants
|
66 participants
n=7 Participants
|
133 participants
n=5 Participants
|
|
History of splenomegaly
Yes
|
22 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
History of splenomegaly
No
|
45 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
95 Participants
n=5 Participants
|
|
Age at index stroke
|
5.6 years
STANDARD_DEVIATION 2.97 • n=5 Participants
|
6.2 years
STANDARD_DEVIATION 2.75 • n=7 Participants
|
5.9 years
STANDARD_DEVIATION 2.87 • n=5 Participants
|
|
Duration of Transfusion
|
7.4 years
STANDARD_DEVIATION 3.85 • n=5 Participants
|
7.0 years
STANDARD_DEVIATION 3.61 • n=7 Participants
|
7.2 years
STANDARD_DEVIATION 3.72 • n=5 Participants
|
|
Prior use of Desferal (deferoxamine mesylate)
Yes
|
47 participants
n=5 Participants
|
44 participants
n=7 Participants
|
91 participants
n=5 Participants
|
|
Prior use of Desferal (deferoxamine mesylate)
No
|
19 participants
n=5 Participants
|
19 participants
n=7 Participants
|
38 participants
n=5 Participants
|
|
Prior use of Desferal (deferoxamine mesylate)
Missing
|
1 participants
n=5 Participants
|
3 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Prior use of Exjade (deferasirox)
Yes
|
57 participants
n=5 Participants
|
55 participants
n=7 Participants
|
112 participants
n=5 Participants
|
|
Prior use of Exjade (deferasirox)
No
|
9 participants
n=5 Participants
|
8 participants
n=7 Participants
|
17 participants
n=5 Participants
|
|
Prior use of Exjade (deferasirox)
Missing
|
1 participants
n=5 Participants
|
3 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Prior use of hydroxyruea
Yes
|
5 participants
n=5 Participants
|
3 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Prior use of hydroxyruea
No
|
62 participants
n=5 Participants
|
63 participants
n=7 Participants
|
125 participants
n=5 Participants
|
|
Liver iron concentration
|
14.5 mg ferritin/gram dry weight liver
n=5 Participants
|
13.9 mg ferritin/gram dry weight liver
n=7 Participants
|
14.5 mg ferritin/gram dry weight liver
n=5 Participants
|
|
History of recurrent stroke
Yes
|
10 participants
n=5 Participants
|
4 participants
n=7 Participants
|
14 participants
n=5 Participants
|
|
History of recurrent stroke
No
|
57 participants
n=5 Participants
|
62 participants
n=7 Participants
|
119 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Because the study was terminated early, time frame is from beginning of treatment until end of treatment (up to 30 Months)Population: The Intent-to-Treat population included all subjects who were randomized and who received any on-study treatment.
Secondary stroke is the first component of the composite primary endpoint and considers the number of participants with recurrent secondary stroke events during 30 months of treatment. Stroke was defined as any clinical event with brain injury due to vascular disease. All neurological events underwent formal stroke adjudication.
Outcome measures
| Measure |
Hydroxyurea/Phlebotomy
n=67 Participants
Hydroxyurea and Phlebotomy Group (Alternative Treatment Arm)
|
Transfusion/Chelation
n=66 Participants
Transfusion and Chelation Group (Standard Treatment Arm)
|
|---|---|---|
|
Occurrence of an Adjudicated Secondary Stroke During the 30-month Treatment Period
Stroke
|
7 participants
|
0 participants
|
|
Occurrence of an Adjudicated Secondary Stroke During the 30-month Treatment Period
No Stroke
|
60 participants
|
66 participants
|
PRIMARY outcome
Timeframe: Because the study was terminated early, time frame is from beginning of treatment until end of treatment (up to 30 Months)Population: Intent-to-treat AND both baseline and 30-month post-treatment LICs.
LIC change-from-baseline is the second component of the composite primary endpoint. LIC was measured by quantitative liver biopsy at baseline and at 30 months or exit from the study.LIC values were transformed into Log10 values prior to computing the change from baseline.
Outcome measures
| Measure |
Hydroxyurea/Phlebotomy
n=31 Participants
Hydroxyurea and Phlebotomy Group (Alternative Treatment Arm)
|
Transfusion/Chelation
n=25 Participants
Transfusion and Chelation Group (Standard Treatment Arm)
|
|---|---|---|
|
Liver Iron Content (LIC) Change-from-baseline
|
-0.006 mg ferritin/gram dry weight liver
Standard Deviation 0.187
|
-0.120 mg ferritin/gram dry weight liver
Standard Deviation 0.387
|
SECONDARY outcome
Timeframe: Baseline, mid-point (week 64), and study exit after up to 30-month treatment period (due to study termination)Population: Intent-to-Treat
The PedsQL(TM) Measurement Model is a modular approach to measuring health-related quality of life (HRQOL) in healthy children and adolescents and those with acute and chronic health conditions. It has a Likert 5-points scale (never to almost always) which were transformed to a 0 to 100 scale based on the PedsQL scoring algorithms, higher scores indicating better quality of life characteristics.
Outcome measures
| Measure |
Hydroxyurea/Phlebotomy
n=67 Participants
Hydroxyurea and Phlebotomy Group (Alternative Treatment Arm)
|
Transfusion/Chelation
n=66 Participants
Transfusion and Chelation Group (Standard Treatment Arm)
|
|---|---|---|
|
Pediatric Quality of Life (PedsQL) - Parent Report (Change From Baseline)
Mid-point: Emotional Functioning Score (n=43,54)
|
-0.99 units on a scale
Standard Deviation 19.709
|
5.56 units on a scale
Standard Deviation 20.366
|
|
Pediatric Quality of Life (PedsQL) - Parent Report (Change From Baseline)
Mid-point: Physical Functioning Score (n=43,64)
|
-1.71 units on a scale
Standard Deviation 33.011
|
-0.57 units on a scale
Standard Deviation 23.195
|
|
Pediatric Quality of Life (PedsQL) - Parent Report (Change From Baseline)
Exit: Physical Functioning Score (n=53, 54)
|
2.27 units on a scale
Standard Deviation 34.456
|
-0.98 units on a scale
Standard Deviation 27.884
|
|
Pediatric Quality of Life (PedsQL) - Parent Report (Change From Baseline)
Exit: School Functioning (n=51,53)
|
-0.29 units on a scale
Standard Deviation 23.074
|
2.83 units on a scale
Standard Deviation 24.564
|
|
Pediatric Quality of Life (PedsQL) - Parent Report (Change From Baseline)
Mid-point : Social Functioning Score (n=42, 54)
|
3.69 units on a scale
Standard Deviation 23.506
|
-0.35 units on a scale
Standard Deviation 20.858
|
|
Pediatric Quality of Life (PedsQL) - Parent Report (Change From Baseline)
Exit : Social Functioning Score (n=53, 54)
|
2.67 units on a scale
Standard Deviation 27.679
|
-1.11 units on a scale
Standard Deviation 27.208
|
|
Pediatric Quality of Life (PedsQL) - Parent Report (Change From Baseline)
Mid-point: Total Functioning Score (n=43, 54)
|
0.39 units on a scale
Standard Deviation 20.411
|
0.20 units on a scale
Standard Deviation 16.974
|
|
Pediatric Quality of Life (PedsQL) - Parent Report (Change From Baseline)
Exit: Total Functioning Score (n=53, 54)
|
1.13 units on a scale
Standard Deviation 24.391
|
1.09 units on a scale
Standard Deviation 20.773
|
|
Pediatric Quality of Life (PedsQL) - Parent Report (Change From Baseline)
Mid-point: Psychosocial Health Summary (n=43,54)
|
1.61 units on a scale
Standard Deviation 16.574
|
0.59 units on a scale
Standard Deviation 17.072
|
|
Pediatric Quality of Life (PedsQL) - Parent Report (Change From Baseline)
Exit: Psychosocial Health Summary (n=53, 54)
|
0.33 units on a scale
Standard Deviation 21.535
|
2.11 units on a scale
Standard Deviation 20.278
|
|
Pediatric Quality of Life (PedsQL) - Parent Report (Change From Baseline)
Exit: Emotional Functioning Score (n=52, 54)
|
-1.25 units on a scale
Standard Deviation 28.265
|
5.65 units on a scale
Standard Deviation 27.676
|
|
Pediatric Quality of Life (PedsQL) - Parent Report (Change From Baseline)
Mid-point: School Functioning (n=43, 54)
|
3.14 units on a scale
Standard Deviation 23.017
|
-3.34 units on a scale
Standard Deviation 22.546
|
SECONDARY outcome
Timeframe: Baseline, midpoint (week 64), and study exit (up to 30 months of treatment)Population: Intent-to-Treat
The PedsQLTM Measurement Model is a modular approach to measuring health-related quality of life (HRQOL) in healthy children and adolescents and those with acute and chronic health conditions. It has a Likert 5-points scale (never to almost always) which were transformed to a 0 to 100 scale based on the PedsQL scoring algorithms, higher scores indicating better quality of life characteristics.
Outcome measures
| Measure |
Hydroxyurea/Phlebotomy
n=67 Participants
Hydroxyurea and Phlebotomy Group (Alternative Treatment Arm)
|
Transfusion/Chelation
n=66 Participants
Transfusion and Chelation Group (Standard Treatment Arm)
|
|---|---|---|
|
Pediatric Quality of Life (PedsQL) - Child Report (Change From Baseline)
Midpoint: Physical Functioning Score (n=47, 57)
|
0.46 units on a scale
Standard Deviation 22.642
|
3.18 units on a scale
Standard Deviation 16.308
|
|
Pediatric Quality of Life (PedsQL) - Child Report (Change From Baseline)
Exit: Physical Functioning Score (n=55, 54)
|
3.41 units on a scale
Standard Deviation 17.639
|
2.03 units on a scale
Standard Deviation 20.426
|
|
Pediatric Quality of Life (PedsQL) - Child Report (Change From Baseline)
Midpoint: Social Functioning Score (n=46, 57)
|
2.39 units on a scale
Standard Deviation 19.909
|
1.84 units on a scale
Standard Deviation 25.011
|
|
Pediatric Quality of Life (PedsQL) - Child Report (Change From Baseline)
Exit: Social Functioning Score (n=54, 54)
|
3.13 units on a scale
Standard Deviation 21.313
|
2.87 units on a scale
Standard Deviation 21.732
|
|
Pediatric Quality of Life (PedsQL) - Child Report (Change From Baseline)
Exit: Total Functioning Score (n=55, 54)
|
2.90 units on a scale
Standard Deviation 16.154
|
2.62 units on a scale
Standard Deviation 16.593
|
|
Pediatric Quality of Life (PedsQL) - Child Report (Change From Baseline)
Midpoint: Psychosocial Health Summary (n=47, 57)
|
0.28 units on a scale
Standard Deviation 17.180
|
3.30 units on a scale
Standard Deviation 18.515
|
|
Pediatric Quality of Life (PedsQL) - Child Report (Change From Baseline)
Exit: Psychosocial Health Summary Score (n=57, 54)
|
2.65 units on a scale
Standard Deviation 17.278
|
2.93 units on a scale
Standard Deviation 16.910
|
|
Pediatric Quality of Life (PedsQL) - Child Report (Change From Baseline)
Midpoint: Emotional Functioning Score (n=47, 57)
|
1.06 units on a scale
Standard Deviation 18.236
|
3.51 units on a scale
Standard Deviation 22.240
|
|
Pediatric Quality of Life (PedsQL) - Child Report (Change From Baseline)
Exit: Emotional Functioning Score (n=55, 54)
|
3.82 units on a scale
Standard Deviation 21.623
|
3.80 units on a scale
Standard Deviation 20.022
|
|
Pediatric Quality of Life (PedsQL) - Child Report (Change From Baseline)
Midpoint: School Functioning Score (n=47, 57)
|
-1.03 units on a scale
Standard Deviation 24.437
|
4.56 units on a scale
Standard Deviation 21.615
|
|
Pediatric Quality of Life (PedsQL) - Child Report (Change From Baseline)
Exit: School Functioning Score (n=55, 53)
|
1.76 units on a scale
Standard Deviation 20.701
|
2.74 units on a scale
Standard Deviation 20.418
|
|
Pediatric Quality of Life (PedsQL) - Child Report (Change From Baseline)
Midpoint: Total Functioning Score (n=47, 57)
|
0.35 units on a scale
Standard Deviation 16.557
|
3.26 units on a scale
Standard Deviation 16.230
|
SECONDARY outcome
Timeframe: Baseline and study exit after up to 30-month treatment period (due to study termination)Population: Intent-to-Treat
The Barthel Index is a measure of activities of daily living (ADL) and assesses the degree of disability in a particular participant. The index records indicators of independence in terms of the disability caused by impairments, such as those that may be sequelae of stroke. The index was used as a record of what the participant did, not as a record of what the participant could do. Barthel scores range from 0 to 100, with higher scores indicating greater independence in daily living activities (caring for oneself).
Outcome measures
| Measure |
Hydroxyurea/Phlebotomy
n=67 Participants
Hydroxyurea and Phlebotomy Group (Alternative Treatment Arm)
|
Transfusion/Chelation
n=66 Participants
Transfusion and Chelation Group (Standard Treatment Arm)
|
|---|---|---|
|
Barthel Index (Change From Baseline)
|
-0.33 units on a scale
Standard Deviation 4.269
|
-0.53 units on a scale
Standard Deviation 6.316
|
SECONDARY outcome
Timeframe: Baseline and study exit after up to 30-month treatment period (due to study termination)Population: Intent-to-Treat. Because the study was terminated, it was not possible to schedule the full battery of neurological assessments on all subjects. Only subjects with both baseline and end of study assessments were included in the analysis.
This test is designed to assess both broad and narrow cognitive abilities in children age 4 years and above as well as to measure major aspects of academic achievement in persons aged 2-90 years. Scaled scores range from 0-100. Higher scores mean better abilities/achievements.
Outcome measures
| Measure |
Hydroxyurea/Phlebotomy
n=67 Participants
Hydroxyurea and Phlebotomy Group (Alternative Treatment Arm)
|
Transfusion/Chelation
n=66 Participants
Transfusion and Chelation Group (Standard Treatment Arm)
|
|---|---|---|
|
Woodcock-Johnson Test of Cognitive Abilities (WJ-C) and Achievement (WJ-III) (Change From Baseline)-Excluding Verbal
General intellectual ability (n=33, 35)
|
-1.64 units on a scale
Standard Deviation 9.594
|
-3.00 units on a scale
Standard Deviation 6.535
|
|
Woodcock-Johnson Test of Cognitive Abilities (WJ-C) and Achievement (WJ-III) (Change From Baseline)-Excluding Verbal
Processing speed (n=35, 33)
|
-0.80 units on a scale
Standard Deviation 14.046
|
2.06 units on a scale
Standard Deviation 13.245
|
|
Woodcock-Johnson Test of Cognitive Abilities (WJ-C) and Achievement (WJ-III) (Change From Baseline)-Excluding Verbal
Working memory (n=33, 34)
|
-7.67 units on a scale
Standard Deviation 22.545
|
-2.65 units on a scale
Standard Deviation 9.435
|
|
Woodcock-Johnson Test of Cognitive Abilities (WJ-C) and Achievement (WJ-III) (Change From Baseline)-Excluding Verbal
Broad attention (n=31, 33)
|
-4.36 units on a scale
Standard Deviation 12.693
|
-0.49 units on a scale
Standard Deviation 8.220
|
|
Woodcock-Johnson Test of Cognitive Abilities (WJ-C) and Achievement (WJ-III) (Change From Baseline)-Excluding Verbal
Executive processes (n=32, 33)
|
-0.72 units on a scale
Standard Deviation 9.323
|
-1.15 units on a scale
Standard Deviation 7.173
|
|
Woodcock-Johnson Test of Cognitive Abilities (WJ-C) and Achievement (WJ-III) (Change From Baseline)-Excluding Verbal
Broad reading (n=34, 33)
|
-0.29 units on a scale
Standard Deviation 8.615
|
-0.94 units on a scale
Standard Deviation 5.172
|
|
Woodcock-Johnson Test of Cognitive Abilities (WJ-C) and Achievement (WJ-III) (Change From Baseline)-Excluding Verbal
Broad math (n=34, 33)
|
-3.53 units on a scale
Standard Deviation 9.542
|
-5.76 units on a scale
Standard Deviation 14.292
|
SECONDARY outcome
Timeframe: Baseline and study exit after up to 30-month treatment period (due to study termination)Population: Intent-to-Treat. Because the study was terminated, it was not possible to schedule the full battery of neurological assessments on all subjects. Only subjects with both baseline and end of study assessments were included in the analysis.
This test is designed to assess both broad and narrow cognitive abilities in children age 4 years and above as well as to measure major aspects of academic achievement in persons aged 2-90 years. Higher scores mean better abilities/achievements. Scaled scores range from 0-100.
Outcome measures
| Measure |
Hydroxyurea/Phlebotomy
n=35 Participants
Hydroxyurea and Phlebotomy Group (Alternative Treatment Arm)
|
Transfusion/Chelation
n=35 Participants
Transfusion and Chelation Group (Standard Treatment Arm)
|
|---|---|---|
|
Woodcock-Johnson Test of Cognitive Abilities (WJ-C) and Achievement (WJ-III) (Change From Baseline)- Verbal Ability
|
1.829 units on a scale
Standard Deviation 8.305
|
-2.487 units on a scale
Standard Deviation 8.806
|
SECONDARY outcome
Timeframe: Baseline to end of study participation (up to 136 weeks)Population: Intent-to-Treat with endpoint data
Outcome measures
| Measure |
Hydroxyurea/Phlebotomy
n=60 Participants
Hydroxyurea and Phlebotomy Group (Alternative Treatment Arm)
|
Transfusion/Chelation
n=60 Participants
Transfusion and Chelation Group (Standard Treatment Arm)
|
|---|---|---|
|
Growth and Development - Height (Change From Baseline to Endpoint)
|
4.40 cm
Standard Deviation 4.32
|
6.61 cm
Standard Deviation 5.87
|
SECONDARY outcome
Timeframe: baseline to end of study participation (up to 136 weeks)Population: Intent-to-Treat with endpoint data
Outcome measures
| Measure |
Hydroxyurea/Phlebotomy
n=64 Participants
Hydroxyurea and Phlebotomy Group (Alternative Treatment Arm)
|
Transfusion/Chelation
n=63 Participants
Transfusion and Chelation Group (Standard Treatment Arm)
|
|---|---|---|
|
Growth and Development - Weight (Change From Baseline to Endpoint)
|
3.83 kg
Standard Deviation 5.07
|
6.36 kg
Standard Deviation 5.43
|
Adverse Events
Hydroxyurea/Phlebotomy
Serious events: 29 serious events
Other events: 65 other events
Deaths: 0 deaths
Transfusion/Chelation
Serious events: 14 serious events
Other events: 65 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Hydroxyurea/Phlebotomy
n=67 participants at risk
Hydroxyurea and Phlebotomy Group (Alternative Treatment Arm)
|
Transfusion/Chelation
n=66 participants at risk
Transfusion and Chelation Group (Standard Treatment Arm)
|
|---|---|---|
|
Blood and lymphatic system disorders
Acute chest syndrome
|
1.5%
1/67 • Number of events 2
|
4.5%
3/66 • Number of events 3
|
|
Cardiac disorders
Right ventricular failure
|
0.00%
0/67
|
1.5%
1/66 • Number of events 1
|
|
Congenital, familial and genetic disorders
Sickle cell anaemia with crisis
|
23.9%
16/67 • Number of events 27
|
7.6%
5/66 • Number of events 7
|
|
Gastrointestinal disorders
Abdominal pain
|
1.5%
1/67 • Number of events 1
|
0.00%
0/66
|
|
Gastrointestinal disorders
Pancreatitis
|
3.0%
2/67 • Number of events 2
|
1.5%
1/66 • Number of events 1
|
|
General disorders
Influenza like illness
|
0.00%
0/67
|
1.5%
1/66 • Number of events 1
|
|
General disorders
Pyrexia
|
6.0%
4/67 • Number of events 4
|
3.0%
2/66 • Number of events 2
|
|
General disorders
Systemic inflammatory response syndrome
|
0.00%
0/67
|
1.5%
1/66 • Number of events 1
|
|
Hepatobiliary disorders
Cholecystitis
|
3.0%
2/67 • Number of events 2
|
1.5%
1/66 • Number of events 1
|
|
Hepatobiliary disorders
Cholelithiasis
|
1.5%
1/67 • Number of events 1
|
1.5%
1/66 • Number of events 1
|
|
Infections and infestations
Cytomegalovirus infection
|
1.5%
1/67 • Number of events 1
|
0.00%
0/66
|
|
Infections and infestations
Escherichia bacteraemia
|
1.5%
1/67 • Number of events 1
|
0.00%
0/66
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/67
|
1.5%
1/66 • Number of events 1
|
|
Infections and infestations
Infusion site infection
|
1.5%
1/67 • Number of events 1
|
0.00%
0/66
|
|
Infections and infestations
Klebsiella sepsis
|
0.00%
0/67
|
1.5%
1/66 • Number of events 1
|
|
Infections and infestations
Mycoplasma infection
|
1.5%
1/67 • Number of events 1
|
0.00%
0/66
|
|
Infections and infestations
Pneumonia
|
1.5%
1/67 • Number of events 1
|
0.00%
0/66
|
|
Infections and infestations
Pyelonephritis
|
3.0%
2/67 • Number of events 2
|
0.00%
0/66
|
|
Infections and infestations
Septic shock
|
1.5%
1/67 • Number of events 1
|
0.00%
0/66
|
|
Infections and infestations
Staphylococcal infection
|
1.5%
1/67 • Number of events 1
|
0.00%
0/66
|
|
Infections and infestations
Urosepsis
|
0.00%
0/67
|
1.5%
1/66 • Number of events 1
|
|
Injury, poisoning and procedural complications
Back injury
|
1.5%
1/67 • Number of events 1
|
0.00%
0/66
|
|
Injury, poisoning and procedural complications
Near drowning
|
0.00%
0/67
|
1.5%
1/66 • Number of events 1
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
1.5%
1/67 • Number of events 1
|
0.00%
0/66
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
1.5%
1/67 • Number of events 1
|
0.00%
0/66
|
|
Nervous system disorders
Cerebrovascular accident
|
9.0%
6/67 • Number of events 7
|
0.00%
0/66
|
|
Nervous system disorders
Convulsion
|
0.00%
0/67
|
1.5%
1/66 • Number of events 1
|
|
Nervous system disorders
Headache
|
1.5%
1/67 • Number of events 2
|
0.00%
0/66
|
|
Nervous system disorders
Intraventricular haemorrhage
|
1.5%
1/67 • Number of events 1
|
0.00%
0/66
|
|
Nervous system disorders
Migraine
|
1.5%
1/67 • Number of events 1
|
0.00%
0/66
|
|
Nervous system disorders
Moyamoya disease
|
0.00%
0/67
|
1.5%
1/66 • Number of events 1
|
|
Nervous system disorders
Transient ischaemic attack
|
1.5%
1/67 • Number of events 1
|
0.00%
0/66
|
|
Renal and urinary disorders
Renal papillary necrosis
|
1.5%
1/67 • Number of events 1
|
0.00%
0/66
|
|
Reproductive system and breast disorders
Ovarian cyst ruptured
|
0.00%
0/67
|
1.5%
1/66 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
1.5%
1/67 • Number of events 1
|
0.00%
0/66
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/67
|
1.5%
1/66 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Status asthmaticus
|
0.00%
0/67
|
1.5%
1/66 • Number of events 1
|
|
Vascular disorders
Angiopathy
|
1.5%
1/67 • Number of events 1
|
0.00%
0/66
|
|
Vascular disorders
Deep vein thrombosis
|
1.5%
1/67 • Number of events 1
|
0.00%
0/66
|
|
Vascular disorders
Thrombosis
|
0.00%
0/67
|
1.5%
1/66 • Number of events 1
|
Other adverse events
| Measure |
Hydroxyurea/Phlebotomy
n=67 participants at risk
Hydroxyurea and Phlebotomy Group (Alternative Treatment Arm)
|
Transfusion/Chelation
n=66 participants at risk
Transfusion and Chelation Group (Standard Treatment Arm)
|
|---|---|---|
|
Blood and lymphatic system disorders
Acute chest syndrome
|
9.0%
6/67 • Number of events 7
|
1.5%
1/66 • Number of events 1
|
|
Blood and lymphatic system disorders
Anaemia
|
29.9%
20/67 • Number of events 39
|
4.5%
3/66 • Number of events 3
|
|
Blood and lymphatic system disorders
Neutropenia
|
14.9%
10/67 • Number of events 13
|
1.5%
1/66 • Number of events 1
|
|
Blood and lymphatic system disorders
Reticulocytopenia
|
31.3%
21/67 • Number of events 30
|
4.5%
3/66 • Number of events 3
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
10.4%
7/67 • Number of events 9
|
1.5%
1/66 • Number of events 5
|
|
Congenital, familial and genetic disorders
Sickle cell anaemia with crisis
|
52.2%
35/67 • Number of events 125
|
43.9%
29/66 • Number of events 75
|
|
Gastrointestinal disorders
Abdominal pain
|
7.5%
5/67 • Number of events 5
|
12.1%
8/66 • Number of events 9
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.0%
4/67 • Number of events 5
|
6.1%
4/66 • Number of events 5
|
|
Gastrointestinal disorders
Nausea
|
7.5%
5/67 • Number of events 5
|
3.0%
2/66 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
17.9%
12/67 • Number of events 15
|
16.7%
11/66 • Number of events 12
|
|
General disorders
Chest pain
|
4.5%
3/67 • Number of events 4
|
6.1%
4/66 • Number of events 4
|
|
General disorders
Pain
|
6.0%
4/67 • Number of events 5
|
7.6%
5/66 • Number of events 5
|
|
General disorders
Pyrexia
|
31.3%
21/67 • Number of events 30
|
30.3%
20/66 • Number of events 37
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
13.4%
9/67 • Number of events 22
|
27.3%
18/66 • Number of events 49
|
|
Infections and infestations
Influenza
|
7.5%
5/67 • Number of events 5
|
7.6%
5/66 • Number of events 5
|
|
Infections and infestations
Sinusitis
|
10.4%
7/67 • Number of events 12
|
3.0%
2/66 • Number of events 2
|
|
Infections and infestations
Upper respiratory tract infection
|
9.0%
6/67 • Number of events 9
|
7.6%
5/66 • Number of events 6
|
|
Infections and infestations
Urinary tract infection
|
7.5%
5/67 • Number of events 6
|
9.1%
6/66 • Number of events 12
|
|
Infections and infestations
Viral infection
|
9.0%
6/67 • Number of events 6
|
6.1%
4/66 • Number of events 4
|
|
Injury, poisoning and procedural complications
Post procedural complication
|
10.4%
7/67 • Number of events 7
|
0.00%
0/66
|
|
Injury, poisoning and procedural complications
Transfusion reaction
|
6.0%
4/67 • Number of events 4
|
15.2%
10/66 • Number of events 14
|
|
Investigations
Alanine aminotransferase increased
|
22.4%
15/67 • Number of events 25
|
21.2%
14/66 • Number of events 36
|
|
Investigations
Aspartate aminotransferase increased
|
20.9%
14/67 • Number of events 23
|
15.2%
10/66 • Number of events 18
|
|
Investigations
Blood creatinine increased
|
9.0%
6/67 • Number of events 7
|
4.5%
3/66 • Number of events 6
|
|
Investigations
Transaminases increased
|
4.5%
3/67 • Number of events 3
|
7.6%
5/66 • Number of events 12
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.0%
2/67 • Number of events 2
|
7.6%
5/66 • Number of events 7
|
|
Nervous system disorders
Convulsion
|
3.0%
2/67 • Number of events 8
|
7.6%
5/66 • Number of events 23
|
|
Nervous system disorders
Dizziness
|
7.5%
5/67 • Number of events 5
|
6.1%
4/66 • Number of events 4
|
|
Nervous system disorders
Headache
|
26.9%
18/67 • Number of events 33
|
33.3%
22/66 • Number of events 33
|
|
Nervous system disorders
Transient ischaemic attack
|
4.5%
3/67 • Number of events 4
|
9.1%
6/66 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
4.5%
3/67 • Number of events 3
|
6.1%
4/66 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.0%
6/67 • Number of events 7
|
6.1%
4/66 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
11.9%
8/67 • Number of events 8
|
4.5%
3/66 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
3.0%
2/67 • Number of events 2
|
12.1%
8/66 • Number of events 11
|
Additional Information
Russell E. Ware, MD, PhD, Director, Texas Children's Hematology Center
Baylor College of Medicine
Phone: (832) 824-1368
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place