Trial Outcomes & Findings for Realizing Effectiveness Across Continents With Hydroxyurea (REACH) (NCT NCT01966731)
NCT ID: NCT01966731
Last Updated: 2025-05-14
Results Overview
An expected toxicity rate of 20% and acceptable toxicity rate of 30% were used for statistical calculations. After 53 participants at each site complete 3 months of therapy, if ≤ 15 participants have hematologic toxicity there is no early evidence against safety. If ≥ 15 of the initial participants experience toxicity, this is early evidence against safety. Future participants will begin at a lower dose of hydroxyurea (10 ± 2.5 mg/kg), with another 53 participants recruited of the same safety analysis. Upon final analysis of 133 participants at the same starting dose, safety for fixed-dose hydroxyurea can be concluded.
ACTIVE_NOT_RECRUITING
PHASE1/PHASE2
635 participants
3 months
2025-05-14
Participant Flow
Participant milestones
| Measure |
Hydroxyurea
Hydroxyurea dosing was administered as a single daily dose, in 200mg, 300mg, 400mg, or 500mg sizes
|
|---|---|
|
Overall Study
STARTED
|
635
|
|
Overall Study
Initiated Hydroxyurea
|
606
|
|
Overall Study
Completed 3 Months of Treatment
|
600
|
|
Overall Study
Completed Study
|
0
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
635
|
Reasons for withdrawal
| Measure |
Hydroxyurea
Hydroxyurea dosing was administered as a single daily dose, in 200mg, 300mg, 400mg, or 500mg sizes
|
|---|---|
|
Overall Study
Death
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Physician Decision
|
2
|
|
Overall Study
Follow up is not complete
|
600
|
|
Overall Study
Screening Failure
|
29
|
|
Overall Study
Found to be ineligible
|
1
|
Baseline Characteristics
Realizing Effectiveness Across Continents With Hydroxyurea (REACH)
Baseline characteristics by cohort
| Measure |
Hydroxyurea
n=606 Participants
Hydroxyurea administered at 15-20 mg/kg/ day as a single daily dose.
|
|---|---|
|
Age, Categorical
<=18 years
|
606 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
|
Sex: Female, Male
Female
|
296 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
310 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
606 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
606 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Region of Enrollment
Angola
|
150 participants
n=93 Participants
|
|
Region of Enrollment
Congo, The Democratic Republic of the
|
156 participants
n=93 Participants
|
|
Region of Enrollment
Uganda
|
149 participants
n=93 Participants
|
|
Region of Enrollment
Kenya
|
151 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 3 monthsPopulation: N= number of participants analyzed for toxicity during the first 3 months of trial therapy
An expected toxicity rate of 20% and acceptable toxicity rate of 30% were used for statistical calculations. After 53 participants at each site complete 3 months of therapy, if ≤ 15 participants have hematologic toxicity there is no early evidence against safety. If ≥ 15 of the initial participants experience toxicity, this is early evidence against safety. Future participants will begin at a lower dose of hydroxyurea (10 ± 2.5 mg/kg), with another 53 participants recruited of the same safety analysis. Upon final analysis of 133 participants at the same starting dose, safety for fixed-dose hydroxyurea can be concluded.
Outcome measures
| Measure |
Hydroxyurea
n=532 Participants
Hydroxyurea dosing was administered as a single daily dose, in 200mg, 300mg, 400mg, or 500mg sizes
|
|---|---|
|
Percentage of Participants With Dose Limiting Toxic Events
|
5.1 percentage of participants
Interval 3.5 to 7.3
|
SECONDARY outcome
Timeframe: Assessed every 4 ± 1 weeks up to 204 monthsThe efficacy of hydroxyurea will be primarily assessed through fetal hemoglobin (HbF), comparing treatment with baseline values. Additional measures of laboratory efficacy will include changes in Hb, MCV, WBC, ANC, ARC, and bilirubin. Clinical events such as vaso-occlusive pain will be captured as secondary outcomes.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Assessed every 4 ± 1 weeks up to 204 monthsHydroxyurea treatment will be dispensed only 35 days at a time, requiring a clinic visit every 4 ± 1 weeks. Medication adherence and the ability for families to adhere to monthly clinic visits are important feasibility outcomes
Outcome measures
Outcome data not reported
Adverse Events
Hydroxyurea
Serious adverse events
| Measure |
Hydroxyurea
n=635 participants at risk
Hydroxyurea administered at 15-20 mg/kg/ day as a single daily dose.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
1.1%
7/635 • Number of events 7 • 67 months
|
|
Blood and lymphatic system disorders
Splenic sequestration
|
1.3%
8/635 • Number of events 9 • 67 months
|
|
Blood and lymphatic system disorders
Vaso-occlusive pain
|
1.3%
8/635 • Number of events 8 • 67 months
|
|
General disorders
Death NOS
|
0.31%
2/635 • Number of events 2 • 67 months
|
|
General disorders
Fever NOS
|
0.31%
2/635 • Number of events 2 • 67 months
|
|
Infections and infestations
Bone infection
|
0.47%
3/635 • Number of events 3 • 67 months
|
|
Infections and infestations
Infection unidentified
|
0.31%
2/635 • Number of events 2 • 67 months
|
|
Infections and infestations
Malaria
|
1.9%
12/635 • Number of events 12 • 67 months
|
|
Infections and infestations
Sepsis
|
1.9%
12/635 • Number of events 12 • 67 months
|
|
Injury, poisoning and procedural complications
Fracture
|
0.16%
1/635 • Number of events 1 • 67 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.16%
1/635 • Number of events 1 • 67 months
|
|
Nervous system disorders
Stroke
|
1.6%
10/635 • Number of events 10 • 67 months
|
|
Respiratory, thoracic and mediastinal disorders
Acute chest syndrome
|
1.3%
8/635 • Number of events 8 • 67 months
|
Other adverse events
| Measure |
Hydroxyurea
n=635 participants at risk
Hydroxyurea administered at 15-20 mg/kg/ day as a single daily dose.
|
|---|---|
|
Blood and lymphatic system disorders
Vaso-occlusive pain
|
55.6%
353/635 • Number of events 755 • 67 months
|
|
General disorders
Fever NOS
|
27.6%
175/635 • Number of events 258 • 67 months
|
|
Infections and infestations
Infection unidentified
|
11.3%
72/635 • Number of events 97 • 67 months
|
|
Infections and infestations
Malaria
|
34.0%
216/635 • Number of events 376 • 67 months
|
|
Infections and infestations
Sepsis
|
5.8%
37/635 • Number of events 41 • 67 months
|
|
Infections and infestations
Skin Infection
|
18.0%
114/635 • Number of events 184 • 67 months
|
|
Infections and infestations
Upper respiratory infection
|
34.3%
218/635 • Number of events 414 • 67 months
|
|
Investigations
Aspartate aminotransferred
|
5.8%
37/635 • Number of events 39 • 67 months
|
|
Investigations
Blood bilirubin increased
|
6.9%
44/635 • Number of events 52 • 67 months
|
|
Investigations
Hemoglobin decreased
|
37.6%
239/635 • Number of events 451 • 67 months
|
|
Investigations
Neutrophil count decreased
|
6.5%
41/635 • Number of events 49 • 67 months
|
|
Investigations
Platelet count decreased
|
10.7%
68/635 • Number of events 106 • 67 months
|
|
Infections and infestations
Reticulocyte count decreased
|
9.9%
63/635 • Number of events 75 • 67 months
|
|
Respiratory, thoracic and mediastinal disorders
Acute chest pain
|
9.3%
59/635 • Number of events 75 • 67 months
|
Additional Information
Russell Ware, MD, PhD
Cincinnati Children's Hospital Medical Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place