Sickle Cell Anemia in ChildrenPhase 3PUSHUPNCT05285917
Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa
A Phase 3 study testing Hydroxyurea in people with Sickle Cell Anemia in Children and Sickle Cell Disease, run by Brown University at 1 site in Angola.
Trial summary
Sickle cell anemia (SCA) is among the world's most common and devastating blood disorders, affecting more than 300,000 newborns per year. Most infants with SCA are born in the low-resource settings of sub- Saharan Africa, where an estimated 50-90% will die before 5 years of age due to lack of early diagnosis and… Read more about this study
- Who is it for?
- Ages 6 months to 12 years
- Conditions the study is for
- Sickle Cell Anemia in Children, Sickle Cell Disease
- What is being tested?
- Hydroxyurea
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 1 siteAngola
- Study dates
- 15 Nov 2023to 1 Sep 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Diagnosis of sickle cell anemia (HbSS or HbS/B0-thalassemia)
- Age 6 months- 12 years of age at enrollment
- Parent or guardian willing and able to provide written or informed consent
- Weight ≥ 7.5 kg (temporary exclusion)
Who cannot join
- Splenomegaly with evidence of hypersplenism as defined by platelet count <150,000, hemoglobin <5 g/dL or absolute neutrophil count <1.0 x10^9/L
- Hydroxyurea use within the past 6 months
- Blood transfusion within the past 6 months (temporary exclusion)
- Pregnancy
- Pre-existing severe hematologic toxicity, as defined by platelet count <80,000, hemoglobin <4 regardless of ANC; hemoglobin <6 AND ARC <100; hemoglobin <7 AND ARC <80 x10^9/L (temporary exclusion)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Angola1 site, 1 recruiting
- Recruiting
Hospital Geral dos Cajueiros
Luanda
Eugenia Alberto Mateus, MSN
About this study
Official title: BrUOG 419 - Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa (PUSHUP)
Sickle cell anemia (SCA) is among the world's most common and devastating blood disorders, affecting more than 300,000 newborns per year. Most infants with SCA are born in the low-resource settings of sub- Saharan Africa, where an estimated 50-90% will die before 5 years of age due to lack of early diagnosis and appropriate care. Hydroxyurea is a safe and effective once-daily oral medication that has become the standard of care for the treatment of children with SCA in high-resource settings. There is now a growing body of evidence to support the safety and clinical benefits of hydroxyurea for the treatment of SCA in sub-Saharan Africa. The requirement for frequent laboratory monitoring, uncertainties about appropriate, most effective dosing, and the concern for hematologic laboratory toxicities, however, will continue to limit widespread hydroxyurea utilization and real-world effectiveness. The investigators have recently developed and prospectively evaluated an individualized, pharmacokinetics-guided hydroxyurea dosing strategy for children with SCA that has demonstrated optimal clinical and laboratory benefits with minimal toxicity. In this research study, the investigators aim to extend this precision medicine approach to Africa.
Read the detailed description
The Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa (PUSHUP) trial is a prospective, randomized clinical trial of hydroxyurea for 400 children with SCA in Luanda, Angola. The study will prospectively evaluate the safety and efficacy of hydroxyurea with limited laboratory monitoring and will bring precision medicine to children with SCA using several novel features including measurement of hydroxyurea using a battery-powered HPLC machine and individualized dose calculations using an automated computer-based algorithm. The objective of this study is to establish evidence-based guidelines for hydroxyurea in sub-Saharan Africa, including appropriate dosing and laboratory monitoring strategy with the goal of allowing for widespread use of hydroxyurea across sub-Saharan Africa, regardless of clinical or laboratory resources.
- Being tested
- Hydroxyurea
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydroxyureaDrug
Also called Hydrea, Droxia
Hydroxyurea has a narrow therapeutic window such that selection of the correct dose is essential to optimize benefits and avoid toxicity.
| Study group | Role | What they receive |
|---|---|---|
| Weight Based Starting Dose | Active comparator | 25 mg/kg starting dose Hydroxyurea Receives: Drug: Hydroxyurea |
| PK-guided starting dose | Experimental | Individualized, PK-guided starting dose Hydroxyurea Receives: Drug: Hydroxyurea |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of clinical, sickle cell adverse events (grade ≥ 3) as assessed by CTCAE v5.0
These events will primarily include vaso-occlusive painful events, acute chest syndrome, stroke, acute splenic sequestration, and death. Data regarding adverse events, including severity grade and relatedness to SCA will be determined on site by the local investigator. All events will be centrally adjudicated by a blinded hematologist who is not a primary study investigator (Medical Safety Monitor) for inclusion in this endpoint.
Measured: From start of study treatment through first 12 months of treatment.
Number of non-SCA related adverse events (grade ≥3), including death as assessed by CTCAE v5.0
The clinical event rate with limited laboratory monitoring will be compared to the 3-months prior to hydroxyurea therapy.
Measured: From start of study treatment through treatment completion, approximately 24 months.
Secondary outcomes (1)
Hematologic response at 12 months
As measured by %HbF, proportion of participants in each arm with HbF ≥ 30%, hemoglobin, absolute reticulocyte count, absolute neutrophil count, platelet count, and mean corpuscular volume), hematologic laboratory toxicities (dose limiting toxicities defined a priori), hospitalizations, death, and all adverse events grade ≥ 3 (SCA and non-SCA related) as assessed by CTCAE v5.0.
Measured: From start of study treatment through first 12 months of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2022
- Study start15 Nov 2023
- Primary completion1 Sep 2026 (estimated)
- Study completion1 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell Anemia in ChildrenStudies of the same condition, open and under way.
- More trials run by Brown UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brown University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Novartis
- Responsible party
- Sponsor
- Investigators
- Patrick T McGann, MD, MS, Principal investigator, Rhode Island Hospital and Hasbro Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05285917
- Sponsor's protocol ID
- BrUOG 419
- Other IDs
- U01HL157872
- Acronym
- PUSHUP
- Status last verified
- Aug 2026
- First submitted
- 1 Mar 2022
- Last updated
- 20 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BrUOG 419 - Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa (PUSHUP)
- ClinicalTrials.gov ID
- NCT05285917
- Acronym / sponsor ID
- PUSHUP / BrUOG 419
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Brown UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Novartis
- Study start
- 15 Nov 2023 (actual)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 1 Sep 2027 (estimated)
- First posted
- 18 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Sickle cell anemia (SCA) is among the world's most common and devastating blood disorders, affecting more than 300,000 newborns per year. Most infants with SCA are born in the low-resource settings of sub- Saharan Africa, where an estimated 50-90% will die before 5 years of age due to lack of early diagnosis and appropriate care. Hydroxyurea is a safe and effective once-daily oral medication that has become the standard of care for the treatment of children with SCA in high-resource settings. There is now a growing body of evidence to support the safety and clinical benefits of hydroxyurea for the treatment of SCA in sub-Saharan Africa. The requirement for frequent laboratory monitoring, uncertainties about appropriate, most effective dosing, and the concern for hematologic laboratory toxicities, however, will continue to limit widespread hydroxyurea utilization and real-world effectiveness. The investigators have recently developed and prospectively evaluated an individualized, pharmacokinetics-guided hydroxyurea dosing strategy for children with SCA that has demonstrated optimal clinical and laboratory benefits with minimal toxicity. In this research study, the investigators aim to extend this precision medicine approach to Africa.
Detailed description
The Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa (PUSHUP) trial is a prospective, randomized clinical trial of hydroxyurea for 400 children with SCA in Luanda, Angola. The study will prospectively evaluate the safety and efficacy of hydroxyurea with limited laboratory monitoring and will bring precision medicine to children with SCA using several novel features including measurement of hydroxyurea using a battery-powered HPLC machine and individualized dose calculations using an automated computer-based algorithm. The objective of this study is to establish evidence-based guidelines for hydroxyurea in sub-Saharan Africa, including appropriate dosing and laboratory monitoring strategy with the goal of allowing for widespread use of hydroxyurea across sub-Saharan Africa, regardless of clinical or laboratory resources.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Weight Based Starting Dose | Active comparator | Drug: Hydroxyurea25 mg/kg starting dose Hydroxyurea |
| PK-guided starting dose | Experimental | Drug: HydroxyureaIndividualized, PK-guided starting dose Hydroxyurea |
Who may qualify
- Ages
- 6 months to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Diagnosis of sickle cell anemia (HbSS or HbS/B0-thalassemia)
- Age 6 months- 12 years of age at enrollment
- Parent or guardian willing and able to provide written or informed consent
- Weight ≥ 7.5 kg (temporary exclusion)
Key exclusion criteria (5 listed)
- Splenomegaly with evidence of hypersplenism as defined by platelet count <150,000, hemoglobin <5 g/dL or absolute neutrophil count <1.0 x10^9/L
- Hydroxyurea use within the past 6 months
- Blood transfusion within the past 6 months (temporary exclusion)
- Pregnancy
- Pre-existing severe hematologic toxicity, as defined by platelet count <80,000, hemoglobin <4 regardless of ANC; hemoglobin <6 AND ARC <100; hemoglobin <7 AND ARC <80 x10^9/L (temporary exclusion)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydroxyureaAlso: Hydrea, DroxiaHydroxyurea has a narrow therapeutic window such that selection of the correct dose is essential to optimize benefits and avoid toxicity. | Drug | PK-guided starting dose, Weight Based Starting Dose |
Primary outcome
Rate of clinical, sickle cell adverse events (grade ≥ 3) as assessed by CTCAE v5.0
Time frame: From start of study treatment through first 12 months of treatment.
These events will primarily include vaso-occlusive painful events, acute chest syndrome, stroke, acute splenic sequestration, and death. Data regarding adverse events, including severity grade and relatedness to SCA will be determined on site by the local investigator. All events will be centrally adjudicated by a blinded hematologist who is not a primary study investigator (Medical Safety Monitor) for inclusion in this endpoint.
Number of non-SCA related adverse events (grade ≥3), including death as assessed by CTCAE v5.0
Time frame: From start of study treatment through treatment completion, approximately 24 months.
The clinical event rate with limited laboratory monitoring will be compared to the 3-months prior to hydroxyurea therapy.
1 secondary outcome
Hematologic response at 12 months
Time frame: From start of study treatment through first 12 months of treatment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Patrick T McGann, MD, MS principal investigator
Rhode Island Hospital and Hasbro Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hydroxyurea in people with Sickle Cell Anemia in Children and Sickle Cell Disease, run by Brown University at 1 site in Angola.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Angola. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact BrUOG (401-863-3000, BrUOG@brown.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of clinical, sickle cell adverse events (grade ≥ 3) as assessed by CTCAE v5.0 (time frame: From start of study treatment through first 12 months of treatment.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2026.