Anemia, Sickle CellTREATNCT02286154
Therapeutic Response Evaluation and Adherence Trial (TREAT)
A study testing Hydroxyurea in people with Anemia, Sickle Cell, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial summary
The primary objectives of this prospective study of hydroxyurea for children with sickle cell anemia are 1) Develop and prospectively evaluate a population pharmacokinetic/pharmacodynamics model to predict the maximum tolerated dose (MTD); 2) Identify urine biomarkers of hydroxyurea adherence using a novel… Read more about this study
- Who is it for?
- Ages 6 months to 21 years
- Conditions the study is for
- Anemia, Sickle Cell
- What is being tested?
- Hydroxyurea
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2014to Dec 2026
- Phase
- Interventional
- 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 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of sickle cell anemia (HbSS or Hbβ0-thalassemia)
- Age 6 months to 21 years at the time of enrollment
- Clinical decision by patient, family, and healthcare provider to initiate hydroxyurea therapy, including patients who are transitioning from chronic transfusions to hydroxyurea therapy
Who cannot join
- 1. Family unwillingness to sign informed consent or comply with study treatments
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: Therapeutic Response Evaluation and Adherence Trial (TREAT): A Prospective Study of Hydroxyurea for Children With Sickle Cell Anemia
The primary objectives of this prospective study of hydroxyurea for children with sickle cell anemia are 1) Develop and prospectively evaluate a population pharmacokinetic/pharmacodynamics model to predict the maximum tolerated dose (MTD); 2) Identify urine biomarkers of hydroxyurea adherence using a novel metabolomics approach; 3) Identify pharmacogenomics modifiers of hydroxyurea MTD; and 4) Longitudinal monitoring of the effect of hydroxyurea upon organ function and quality of life.
Read the detailed description
There is now ample clinical evidence that hydroxyurea is a safe and effective medication for adults and children with sickle cell anemia (SCA), and most hematologists agree the short-term safety and efficacy of hydroxyurea has been proven. The National Heart, Lung, and Blood Institute have recently released evidence-based guidelines for SCA, recommending that hydroxyurea be offered to all affected children as young as nine months of age, regardless of clinical severity. Despite the overwhelming evidence demonstrating safety and efficacy, hydroxyurea remains underutilized for a variety of reasons. In this prospective study, the investigators will utilize innovative strategies designed to address and overcome some of the barriers that currently limit the use of hydroxyurea for children with SCA. The investigators will utilize novel laboratory techniques and pharmacometric modeling in order to accurately predict the most effective hydroxyurea dose referred to as the maximum tolerated dose. The investigators aim to develop a screening urine test to objectively and accurately determine adherence to hydroxyurea therapy. In addition, the study will document critical laboratory and clinical characteristics of this unique population of patients with SCA who begin hydroxyurea at a young age.
This study will follow two groups of patients. The first group, referred to as the New Cohort, will include mostly young infants who are not receiving hydroxyurea therapy upon entering the study. The starting dose of hydroxyurea for each of the participants in the New Cohort will be individually determined using the novel population PK/PD dose-prediction model. The second group of study participants, referred to as the Old Cohort, will include patients who are already receiving hydroxyurea therapy upon study entry. Both the Old and New Cohort (New Cohort) will be included in the development of a urine biomarker of adherence and will be followed throughout the study to document the effect hydroxyurea has upon organ function and quality of life. It is important to note that this is not a therapeutic drug trial. Prior to enrollment in the study, participants, along with their families and clinical providers, have decided to initiate hydroxyurea therapy for clinical indications. Except for the dose prediction model for the New Cohort, participants will be treated and monitored according to the routine clinical practice guidelines of the Cincinnati Children's Hospital Comprehensive Sickle Cell Center.
- Conditions
- Anemia, Sickle Cell
- Being tested
- Hydroxyurea
- Keywords
- Hydroxyurea, Sickle Cell, Pharmacokinetics, dynamics, genomics
- 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
For New Cohort participants, PK/PD data will be used to predict the most effective maximum tolerated dose. Old Cohort participants will receive hydroxyurea escalated to MTD as per local clinical guidelines.
| Study group | Role | What they receive |
|---|---|---|
| Hydroxyurea | Experimental | All enrolled participants will receive hydroxyurea, but upon enrollment, participants will be identified as part of the "New Cohort" or "Old Cohort" "New Cohort" participants include those who are not receiving hydroxyurea therapy upon study entry. "Old Cohort" participants include those who are already receiving hydroxyurea therapy upon study entry. New Cohort participants will have starting dose predicted using PK/PD data and Old Cohort participants will continue dosing per clinical guidelines. Receives: Drug: Hydroxyurea |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Reach Maximum Tolerated Dose (months)
Time it takes to reach maximum tolerated dose (MTD) of hydroxyurea quantified in months.
Measured: Twelve months
Secondary outcomes (7)
Hydroxyurea adherence
Hydroxyurea adherence as measured by analysis of urine metabolites
Measured: Monthly until MTD then yearly up to ten years
Neurological function
Neurological function as measured by transcranial Doppler study (yearly), brain MRI (every 5 years beginning at age 5).
Measured: Yearly
Non-invasive Transcranial Cerebral Oximetry
Non-invasive transcranial cerebral oximetry
Measured: Monthly until MTD then every six months, up to ten years
Splenic function
Splenic function as measured by pocked red blood cell counts ("pit counts")
Measured: Annually up to ten years
Kidney function
Kidney function as measured by BUN/creatinine, urinalysis, and cystatin-C
Measured: Annually, up to ten years
Cardiac function (assessment and growth)
Cardiac function as measured by echocardiogram and ECG
Measured: Every Five Years, up to 21 years of age
Assessment of Growth
Assessment of growth as defined by height and weight
Measured: Every six months, up to ten years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2014 (estimated)
- Study startOct 2014
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Anemia, Sickle CellStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Charles Quinn, MD, MS, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02286154
- Sponsor's protocol ID
- CCHMC_TREAT
- Acronym
- TREAT
- Status last verified
- Jul 2025
- First submitted
- 1 Oct 2014
- Last updated
- 17 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
Publications
Power-Hays A, Kincaid A, McElhinney KE, Latham TS, Quinn CT, Frenck RW, Ware RE. Seroprotection after measles vaccination in children with sickle cell anemia receiving hydroxyurea. Blood Adv. 2026 Sep 22;10(18):6249-6254. doi: 10.1182/bloodadvances.2026019674.
PubMed 42448315Power-Hays A, McElhinney KE, Williams TN, Mochamah G, Olupot-Olupot P, Paasi G, Reid ME, Rankine-Mullings AE, Opoka RO, John CC, McGann PT, Quinn CT, Punt NC, Smart LR, Stuber SE, Latham TS, Vinks AA, Ware RE. Hydroxyurea pharmacokinetics in children with sickle cell anemia across different global populations. Blood Adv. 2026 Jan 27;10(2):418-427. doi: 10.1182/bloodadvances.2025017254.
PubMed 41026975Quinn CT, Niss O, Dong M, Pfeiffer A, Korpik J, Reynaud M, Bonar H, Kalfa TA, Smart LR, Malik P, Ware RE, Vinks AA, McGann PT. Early initiation of hydroxyurea (hydroxycarbamide) using individualised, pharmacokinetics-guided dosing can produce sustained and nearly pancellular expression of fetal haemoglobin in children with sickle cell anaemia. Br J Haematol. 2021 Aug;194(3):617-625. doi: 10.1111/bjh.17663. Epub 2021 Jul 5.
PubMed 34227124Sadaf A, Quinn CT, Korpik JB, Pfeiffer A, Reynaud M, Niss O, Malik P, Ware RE, Kalfa TA, McGann PT. Rapid and automated quantitation of dense red blood cells: A robust biomarker of hydroxyurea treatment response. Blood Cells Mol Dis. 2021 Sep;90:102576. doi: 10.1016/j.bcmd.2021.102576. Epub 2021 May 11. No abstract available.
PubMed 34020272McGann PT, Niss O, Dong M, Marahatta A, Howard TA, Mizuno T, Lane A, Kalfa TA, Malik P, Quinn CT, Ware RE, Vinks AA. Robust clinical and laboratory response to hydroxyurea using pharmacokinetically guided dosing for young children with sickle cell anemia. Am J Hematol. 2019 Aug;94(8):871-879. doi: 10.1002/ajh.25510. Epub 2019 Jun 12.
PubMed 31106898Dong M, McGann PT, Mizuno T, Ware RE, Vinks AA. Development of a pharmacokinetic-guided dose individualization strategy for hydroxyurea treatment in children with sickle cell anaemia. Br J Clin Pharmacol. 2016 Apr;81(4):742-52. doi: 10.1111/bcp.12851. Epub 2016 Feb 5.
PubMed 26615061
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutic Response Evaluation and Adherence Trial (TREAT): A Prospective Study of Hydroxyurea for Children With Sickle Cell Anemia
- ClinicalTrials.gov ID
- NCT02286154
- Acronym / sponsor ID
- TREAT / CCHMC_TREAT
- Conditions
- Anemia, Sickle Cell
- Keywords
- Hydroxyurea, Sickle Cell, Pharmacokinetics, dynamics, genomics
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Study start
- Oct 2014 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 7 Nov 2014 (estimated)
- 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.
The primary objectives of this prospective study of hydroxyurea for children with sickle cell anemia are 1) Develop and prospectively evaluate a population pharmacokinetic/pharmacodynamics model to predict the maximum tolerated dose (MTD); 2) Identify urine biomarkers of hydroxyurea adherence using a novel metabolomics approach; 3) Identify pharmacogenomics modifiers of hydroxyurea MTD; and 4) Longitudinal monitoring of the effect of hydroxyurea upon organ function and quality of life.
Detailed description
There is now ample clinical evidence that hydroxyurea is a safe and effective medication for adults and children with sickle cell anemia (SCA), and most hematologists agree the short-term safety and efficacy of hydroxyurea has been proven. The National Heart, Lung, and Blood Institute have recently released evidence-based guidelines for SCA, recommending that hydroxyurea be offered to all affected children as young as nine months of age, regardless of clinical severity. Despite the overwhelming evidence demonstrating safety and efficacy, hydroxyurea remains underutilized for a variety of reasons. In this prospective study, the investigators will utilize innovative strategies designed to address and overcome some of the barriers that currently limit the use of hydroxyurea for children with SCA. The investigators will utilize novel laboratory techniques and pharmacometric modeling in order to accurately predict the most effective hydroxyurea dose referred to as the maximum tolerated dose. The investigators aim to develop a screening urine test to objectively and accurately determine adherence to hydroxyurea therapy. In addition, the study will document critical laboratory and clinical characteristics of this unique population of patients with SCA who begin hydroxyurea at a young age.
This study will follow two groups of patients. The first group, referred to as the New Cohort, will include mostly young infants who are not receiving hydroxyurea therapy upon entering the study. The starting dose of hydroxyurea for each of the participants in the New Cohort will be individually determined using the novel population PK/PD dose-prediction model. The second group of study participants, referred to as the Old Cohort, will include patients who are already receiving hydroxyurea therapy upon study entry. Both the Old and New Cohort (New Cohort) will be included in the development of a urine biomarker of adherence and will be followed throughout the study to document the effect hydroxyurea has upon organ function and quality of life. It is important to note that this is not a therapeutic drug trial. Prior to enrollment in the study, participants, along with their families and clinical providers, have decided to initiate hydroxyurea therapy for clinical indications. Except for the dose prediction model for the New Cohort, participants will be treated and monitored according to the routine clinical practice guidelines of the Cincinnati Children's Hospital Comprehensive Sickle Cell Center.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hydroxyurea | Experimental | Drug: HydroxyureaAll enrolled participants will receive hydroxyurea, but upon enrollment, participants will be identified as part of the "New Cohort" or "Old Cohort" "New Cohort" participants include those who are not receiving hydroxyurea therapy upon study entry. "Old Cohort" participants include those who are already receiving hydroxyurea therapy upon study entry. New Cohort participants will have starting dose predicted using PK/PD data and Old Cohort participants will continue dosing per clinical guidelines. |
Who may qualify
- Ages
- 6 months to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Diagnosis of sickle cell anemia (HbSS or Hbβ0-thalassemia)
- Age 6 months to 21 years at the time of enrollment
- Clinical decision by patient, family, and healthcare provider to initiate hydroxyurea therapy, including patients who are transitioning from chronic transfusions to hydroxyurea therapy
Key exclusion criteria (1 listed)
- 1. Family unwillingness to sign informed consent or comply with study treatments
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 |
|---|---|---|
| HydroxyureaFor New Cohort participants, PK/PD data will be used to predict the most effective maximum tolerated dose. Old Cohort participants will receive hydroxyurea escalated to MTD as per local clinical guidelines. | Drug | Hydroxyurea |
Primary outcome
Time to Reach Maximum Tolerated Dose (months)
Time frame: Twelve months
Time it takes to reach maximum tolerated dose (MTD) of hydroxyurea quantified in months.
7 secondary outcomes
Hydroxyurea adherence
Time frame: Monthly until MTD then yearly up to ten years
Neurological function
Time frame: Yearly
Non-invasive Transcranial Cerebral Oximetry
Time frame: Monthly until MTD then every six months, up to ten years
Splenic function
Time frame: Annually up to ten years
Kidney function
Time frame: Annually, up to ten years
Cardiac function (assessment and growth)
Time frame: Every Five Years, up to 21 years of age
Assessment of Growth
Time frame: Every six months, up to ten years
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 17 Jul 2025.
- Derived from this study: PubMed 42448315Power-Hays A, Kincaid A, McElhinney KE, Latham TS, Quinn CT, Frenck RW, Ware RE. Seroprotection after measles vaccination in children with sickle cell anemia receiving hydroxyurea. Blood Adv. 2026 Sep 22;10(18):6249-6254. doi: 10.1182/bloodadvances.2026019674.
- Derived from this study: PubMed 41026975Power-Hays A, McElhinney KE, Williams TN, Mochamah G, Olupot-Olupot P, Paasi G, Reid ME, Rankine-Mullings AE, Opoka RO, John CC, McGann PT, Quinn CT, Punt NC, Smart LR, Stuber SE, Latham TS, Vinks AA, Ware RE. Hydroxyurea pharmacokinetics in children with sickle cell anemia across different global populations. Blood Adv. 2026 Jan 27;10(2):418-427. doi: 10.1182/bloodadvances.2025017254.
- Derived from this study: PubMed 34227124Quinn CT, Niss O, Dong M, Pfeiffer A, Korpik J, Reynaud M, Bonar H, Kalfa TA, Smart LR, Malik P, Ware RE, Vinks AA, McGann PT. Early initiation of hydroxyurea (hydroxycarbamide) using individualised, pharmacokinetics-guided dosing can produce sustained and nearly pancellular expression of fetal haemoglobin in children with sickle cell anaemia. Br J Haematol. 2021 Aug;194(3):617-625. doi: 10.1111/bjh.17663. Epub 2021 Jul 5.
- Derived from this study: PubMed 34020272Sadaf A, Quinn CT, Korpik JB, Pfeiffer A, Reynaud M, Niss O, Malik P, Ware RE, Kalfa TA, McGann PT. Rapid and automated quantitation of dense red blood cells: A robust biomarker of hydroxyurea treatment response. Blood Cells Mol Dis. 2021 Sep;90:102576. doi: 10.1016/j.bcmd.2021.102576. Epub 2021 May 11. No abstract available.
- Derived from this study: PubMed 31106898McGann PT, Niss O, Dong M, Marahatta A, Howard TA, Mizuno T, Lane A, Kalfa TA, Malik P, Quinn CT, Ware RE, Vinks AA. Robust clinical and laboratory response to hydroxyurea using pharmacokinetically guided dosing for young children with sickle cell anemia. Am J Hematol. 2019 Aug;94(8):871-879. doi: 10.1002/ajh.25510. Epub 2019 Jun 12.
- Derived from this study: PubMed 26615061Dong M, McGann PT, Mizuno T, Ware RE, Vinks AA. Development of a pharmacokinetic-guided dose individualization strategy for hydroxyurea treatment in children with sickle cell anaemia. Br J Clin Pharmacol. 2016 Apr;81(4):742-52. doi: 10.1111/bcp.12851. Epub 2016 Feb 5.
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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. This study is not recruiting at the moment.
Charles Quinn, MD, MS principal investigator
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hydroxyurea in people with Anemia, Sickle Cell, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
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 3 inclusion and 1 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: under way, not looking for participants, as of the sponsor's last update on 17 Jul 2025. 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 United States. 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.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Reach Maximum Tolerated Dose (months) (time frame: Twelve months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02286154, which also lists 6 linked publications.
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 17 Jul 2025.