Effectiveness of Nontraditional Hydroxyurea Algorithms: Novel and Clinical Evaluations (ENHANCE)
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age6+
SponsorChildren's Hospital Medical Center, Cincinnati
About this trial
The main reason for this research study is to learn more about hydroxyurea and the treatment of sickle cell anemia (SCA). Hydroxyurea is a medication that has been studied for many years and has been shown to provide benefits for people with SCA.
In this research study, the investigators hope to learn more about how to improve the dosing and monitoring of hydroxyurea and learn more about the long-term effects of hydroxyurea over time. Hydroxyurea is usually dosed based only on your weight. Our study will use a new way to select a starting dose that is based on how each patient absorbs hydroxyurea.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Diagnosis of sickle cell anemia (HbSS) or sickle-β0-thalassemia (HbSβ0)
Age 6 months at the time of enrollment
Clinical decision by patient, family, and healthcare provider to initiate hydroxyurea therapy
Disqualifiers
Current treatment with regularly scheduled blood transfusions
Sickle-hemoglobin C disease (HbSC), sickle-β+-thalassemia (HbSβ+)
Trial design
Design model
Single group
Treatments tested in this trial
PK-optimized oral hydroxyurea at MTD until 15 years of age.
DrugBecause people are different, we will measure how each participant's body absorbs and eliminates the medicine, hydroxyurea, using blood tests. This information will be used to determine the best dose for each participant (rather than using the same weight-based dose for everyone).
Treatment groups
50 Participants
are divided into 1 treatment groupGroup A: Observational Treatment Group (Single Arm)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Composite Organ Injury
Evidence of injury in any of four critical organ systems: brain, kidney, heart, or spleen. Participants will be classified as having met the composite endpoint if they fulfill at least one of the organ-specific criteria listed: cerebral infarction (silent or overt) or steno-occlusive vasculopathy by MRI of brain; urine albumin-to-creatinine ratio (UACR) \> 300 mg/g; extracellular volume fraction (ECV) \> 0.35 on cardiac MRI; or erythrocyte pit count \< 5%
Time frame
Through study completion, an average of 10 yearsSecondary outcomes
1
longitudinal change in fetal hemoglobin percentage (HbF%)
HbF is a well-established mechanistic surrogate marker in SCA that is strongly associated with reduced sickling and organ injury across multiple organ systems. This endpoint will quantify the sustained biological effectiveness of early PK-guided hydroxyurea dosing.
Time frame
Through study completion, an average of 10 years2
Longitudinal change in hemoglobin concentration (g/dL)
A beneficial laboratory response to hydroxyurea would include less severe anemia (measured by hemoglobin concentration). This is reported in a complete blood count (CBC).
Time frame
Through study completion, an average of 10 years.3
Longitudinal change in reticulocyte count (10^9/L)
A beneficial laboratory response to hydroxyurea would include a decreased reticulocyte count, indicating less severe anemia. This is reported with a complete blood count (CBC).
Time frame
Through study completion, an average of 10 years.4
Longitudinal change in absolute neutrophil count (10^9/L)
A surrogate marker of hydroxyurea effectiveness and adherence is the absolute neutrophil count (ANC). Hydroxyurea is titrated according to the ANC. This is reported in a complete blood count (CBC) with differential leukocyte count.
Time frame
Through study completion, an average of 10 years.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Children's Hospital Medical Center, Cincinnati
Lead sponsor
Greater Cincinnati Foundation
Collaborator
Source ClinicalTrials.gov