Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Hydroxyurea Management in Kids: Intensive Versus Stable Dosage Strategies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03020615
Recruitment Status : Completed
First Posted : January 13, 2017
Results First Posted : June 25, 2021
Last Update Posted : June 25, 2021
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
This is a pilot study, single-blind, randomized, multicenter, therapeutic clinical trial designed to evaluate the feasibility of enrolling infants and toddlers (9 months to 36 months) with sickle cell anemia (SCA; HbSS or HbSβ^0thalassemia), regardless of disease severity, to a therapeutic trial. A prior clinical trial at St. Jude Children's Research Hospital (SJCRH) (BABYHUG, NCT01783990) demonstrated that a fixed dose (20 mg/kg/day) of hydroxyurea was safe and effective in decreasing SCA-related complications in very young children (9-18 months), and largely due to these findings, hydroxyurea is recommended to be offered to all children (≥9 months old) with SCA, independent of disease severity. Nevertheless, children in the treatment arm of BABYHUG continued to experience vaso-occlusive symptoms and to incur organ damage. In clinical trials of older children with SCA, intensification of hydroxyurea to a maximum tolerated dosage (MTD), defined by mild to moderate myelosuppression, may be associated with improved laboratory parameters compared to fixed lower-dosing, but the clinical benefits gained from dose intensification have not been described. Therefore, in this trial, children in the standard treatment arm will receive a fixed dose of hydroxyurea (20 mg/kg/day), and participants in the experimental arm will receive hydroxyurea intensified to MTD, defined by a goal absolute neutrophil count (ANC) of 1500-3000 cells/µL. This trial aims to establish a multicenter infrastructure that will identify, enroll and randomize very young children (9-36 months) to receive fixed dose versus intensified-dose hydroxyurea in a single blinded manner, and to obtain prospective pilot data comparing the clinical and laboratory outcomes between the treatment arms to facilitate design of a definitive phase III trial.

Condition or disease Intervention/treatment Phase
Sickle Cell Anemia Drug: Hydroxyurea Phase 2

Detailed Description:

All participants will initially receive hydroxyurea at a dose of ~20 mg/kg/day in an open label fashion for eight weeks (± 2 weeks) prior to randomization. Participants will receive monthly medical evaluations (every 4 ± 2 weeks) where they will have height and weight measurements, medical history, physical examination, and medication adherence assessments. During these monthly visits complete blood counts with absolute reticulocyte count will be monitored. Hemoglobin electrophoresis, complete serum chemistries, urinalysis, lactate dehydrogenase and quality of life measurements will be obtained every 20 (±2) weeks. Transcranial Doppler (TCD) ultrasound velocities will be obtained at study entry (in participants ≥2 years of age) and study exit. Participants randomized to receive hydroxyurea at MTD will have their dose increased by 5 mg/kg/day every 8 weeks, in the absence of toxicity, until a goal ANC of 1500-3000 cells/µL is achieved, up to a maximum of 35 mg/kg/day.

Both groups will receive their assigned treatment for 48 weeks (± 3 weeks). Participants will be in the study for a total of 56 weeks (± 3 weeks) and have 14 clinic visits to the St. Jude outpatient Hematology Clinic during that time. After the 56 weeks, participants will be followed for an additional 30 days for side effects and will then be taken off study.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Official Title: Hydroxyurea Management in Kids: Intensive Versus Stable Dosage Strategies
Actual Study Start Date : May 12, 2017
Actual Primary Completion Date : June 8, 2020
Actual Study Completion Date : June 8, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia
Drug Information available for: Hydroxyurea

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Active Comparator: Stable Dosing
In the first 8 weeks (± 2 weeks) of this study, participants will receive standard treatment [a fixed dose of 20 (± 2.5) mg/kg/day of hydroxyurea]. After 8 weeks (± 2 weeks) of standard treatment, participants will be randomized (like flipping a coin) to one of two treatment groups. Group 1 (Stable Dosing) continues standard treatment.
 Drug: Hydroxyurea
Given orally once daily.
Other Name: HU
Experimental: Intensive Dosing
In the first 8 weeks (± 2 weeks) of this study, participants will receive standard treatment [a fixed dose of 20 (± 2.5) mg/kg/day of hydroxyurea]. After 8 weeks (± 2 weeks) of standard treatment, participants will be randomized (like flipping a coin) to one of two treatment groups. Group 2 (Intensive Dosing) will have their HU dose increased by 5 mg/kg/day every 8 weeks up to a maximum of 35 mg/kg/day.
 Drug: Hydroxyurea
Given orally once daily.
Other Name: HU


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Number of Patients Enrolled. [ Time Frame: at baseline ]
    A count of the number of patients enrolled will be provided.

  2. Number of Patients Randomized [ Time Frame: Eight weeks (± 2 weeks) after study enrollment ]
    A count of the number of patients randomized will be provided.

  3. Number of Randomized Patients With ≥80% Chronic Medication Compliance [ Time Frame: At completion of therapy, up to 56 weeks after study enrollment ]
    Chronic medication compliance is defined based on medication possession ratio (MPR), a measure of the percentage of time that a patient has access to medication. Each participant's MPR is calculated as [(days medication in family's possession/days prescribed medication) * 100].

  4. Number of Patients Who Have the % Fetal Hemoglobin (%HbF) Collected at Baseline and at Study Exit [ Time Frame: At baseline and at completion of the protocol, up to 56 weeks after study enrollment ]
    The number of patients who have successfully provided %HbF at baseline and study exit will be provided.


Secondary Outcome Measures :
  1. Frequency by Reason Given for Refusal for Study Participation [ Time Frame: Once, at enrollment ]
    Descriptive statistics of count and frequency will be provided for participants who were approached but refused to be enrolled on the study.

  2. Number of Patients With Hospitalizations by Arm [ Time Frame: From baseline through completion of therapy, up to 56 weeks ]
    The number of patients with hospitalizations will be provided by arm. This analysis approach is different than what was written in the protocol due to small number of participants with hospitalizations and small number of hospitalization events.

  3. Cumulative Number of Hospitalizations by Arms [ Time Frame: From baseline through completion of therapy, up to 56 weeks ]
    The total number of hospitalization events will be provided by arms. This analysis approach is different than what was written in the protocol due to small number of participants with hospitalizations and small number of hospitalization events.

  4. Mean Change in Hemoglobin (g/dL) [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test.

  5. Median Change in Hemoglobin (g/dL) [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Descriptive statistics of the change between baseline and completion of the study will be provided.

  6. Mean Change in Fetal Hemoglobin (%) [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Descriptive statistics of the change between baseline and completion of the study will be provided.

  7. Median Change in Fetal Hemoglobin (%) [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test.

  8. Mean Change in Mean Corpuscular Volume (fL) [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Descriptive statistics of the change between baseline and completion of the study will be provided.

  9. Median Change in Mean Corpuscular Volume (fL) [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test.

  10. Mean Change in Absolute Reticulocyte Count (*10^3 Reticulocytes/µL) [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test.

  11. Median Change in Absolute Reticulocyte Count (*10^3 Reticulocytes/µL) [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Descriptive statistics of the change between baseline and completion of the study will be provided.

  12. Mean Change in White Blood Cell Count (*10^3 White Blood Cells/µL) [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Descriptive statistics of the change between baseline and completion of the study will be provided.

  13. Median Change in White Blood Cell Count (*10^3 White Blood Cells/µL) [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test.

  14. Mean Change in Absolute Neutrophil Count (*10^3 Neutrophils/µL) [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Descriptive statistics of the change between baseline and completion of the study will be provided.

  15. Median Change in Absolute Neutrophil Count (*10^3 Neutrophils/µL) [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test.

  16. Mean Change in Platelet Count (*10^3 Platelets/µL) [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Descriptive statistics of the change between baseline and completion of the study will be provided.

  17. Median Change in Platelet Count (*10^3 Platelets/µL) [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test.

  18. Mean Change in Bilirubin (mg/dL) [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Descriptive statistics of the change between baseline and completion of the study will be provided.

  19. Median Change in Bilirubin (mg/dL) [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test.

  20. Mean Change in Lactate Dehydrogenase (Units/L) [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test.

  21. Median Change in Lactate Dehydrogenase (Units/L) [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Descriptive statistics of the change between baseline and completion of the study will be provided.

  22. Number of Participants Who do Not Have Normal Transcranial Doppler (TCD) Ultrasound Velocities [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Normal TCD velocities will be defined as TCD velocities <170 cm/s.

  23. Number of Participants Who Undergo Surgery [ Time Frame: From start of therapy through completion of therapy, up to 56 weeks ]
    Any operative procedure will be included.

  24. Number of Participants Who Undergo Transfusion [ Time Frame: From start of therapy through completion of therapy, up to 56 weeks ]
    Transfusion will be defined as the provision of red blood cells to correct anemia.

  25. Number of Patients With Toxicities Related to Hydroxyurea Dosing [ Time Frame: From start of therapy through completion of therapy, up to 56 weeks ]
    Number of patients with toxicities to include: neutropenia (ANC <1000*/µL), reticulocytopenia (ARC <80*10^3/µL and concomitant anemia (hemoglobin <6 g/dL), and thrombocytopenia (platelets <100*10^3/µL).

  26. Number of Toxicities Related to Hydroxyurea Dosing [ Time Frame: From start of therapy through completion of therapy, up to 56 weeks ]
    Number of toxicities will be reported to include: neutropenia (ANC <1000*/µL), reticulocytopenia (ARC <80*10^3/µL and concomitant anemia (hemoglobin <6 g/dL), and thrombocytopenia (platelets <100*10^3/µL).

  27. Change in Pain and Hurt Score [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score.

  28. Change in Pain Impact Score [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score.

  29. Change in Pain Management Score [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score.

  30. Change in Worry I Score [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score.

  31. Change in Worry II Score [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score.

  32. Change in Emotions Score [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score.

  33. Change in Treatment Score [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score.

  34. Change in Communication I Score [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score.

  35. Change in Communication II Score [ Time Frame: From baseline at study entry to completion of therapy, up to 56 weeks ]
    Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   9 Months to 36 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Children with HbSS or sickle hemoglobin (HbS)/β^0thalassemia
  • ≥9 to ≤ 36 months of age at study initiation
  • Enrollment will occur irrespective of clinical severity

Exclusion Criteria:

Permanent:

  • Receiving chronic red blood cell transfusion therapy.
  • Condition or chronic illness, which in the opinion of the PI makes participation unsafe.

Transient (participants may be re-evaluated after ≥14 days):

  • Recent (<30 days) participation in another clinical intervention trial utilizing an investigational new drug/investigational device exemption (IND/IDE) agent.
  • Erythrocyte transfusion in the past 2 months.

  • Laboratory Assessments:

    • Hemoglobin <6.0 g/dL
    • Absolute reticulocyte count <80 * 10^3/µL if hemoglobin <9.0 mg/dL
    • Absolute neutrophil count <1.5 * 10^3/µL
    • Platelet count <100 * 10^3/µL
    • Serum creatinine > twice the upper limit of normal for age
    • Alanine aminotransferase (ALT) > twice the upper limit of normal
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03020615


Locations
Layout table for location information
United States, Georgia
Emory University/Children's Health Care of Atlanta
Atlanta, Georgia, United States, 30322
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390-9063
Sponsors and Collaborators
St. Jude Children's Research Hospital
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Layout table for investigator information
Principal Investigator: Jeremie Estepp, MD St. Jude Children's Research Hospital
  Study Documents (Full-Text)

Documents provided by St. Jude Children's Research Hospital:
Study Protocol and Statistical Analysis Plan  [PDF] March 9, 2020

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Layout table for additonal information
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT03020615    
Other Study ID Numbers: HUGKISS
R34HL127162 ( U.S. NIH Grant/Contract )
First Posted: January 13, 2017    Key Record Dates
Results First Posted: June 25, 2021
Last Update Posted: June 25, 2021
Last Verified: May 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by St. Jude Children's Research Hospital:
Sickle cell
Hydroxyurea
Infants
Additional relevant MeSH terms:
Layout table for MeSH terms
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
 Hydroxyurea
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors