Hydroxyurea to Prevent Organ Damage in Children With Sickle Cell Anemia
NCT ID: NCT00006400
Last Updated: 2020-08-19
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
193 participants
INTERVENTIONAL
2000-08-31
2009-09-30
Brief Summary
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Detailed Description
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In 1995, the Multicenter Study of Hydroxyurea (MSH) demonstrated that hydroxyurea is effective in decreasing the frequency of painful crises, hospitalizations for crises, acute chest syndrome, and blood transfusions by 50%. The recently completed phase II study of hydroxyurea in children (PED HUG) demonstrated that children have a response to hydroxyurea similar to that seen in adults in terms of increasing fetal hemoglobin levels and total hemoglobin, and decreasing complications associated with sickle cell anemia. In addition, this study demonstrated that the drug does not adversely affect growth and development between the ages of 5 and 15. A recently completed pilot study of hydroxyurea given to children between the ages of 6 months and 24 months demonstrated that the drug is tolerated well by small infant, and that the fetal hemoglobin switch can be forced to remain in the "on position" by hydroxyurea administration.
A Special Emphasis Panel (SEP) met on April 12, 1996 to review the results of the MSH trial and the progress to date of the PED HUG study. The SEP recommended that NHLBI undertake the BABY HUG trial.
DESIGN NARRATIVE:
BABY HUG is a randomized, double-blind, placebo-controlled study to determine if hydroxyurea can prevent the onset of chronic end organ damage in young children with sickle cell anemia. Approximately 200 children with sickle cell disease will be recruited to receive either hydroxyurea or placebo. The children will be screened at study entry for signs of abnormal brain, kidney, pulmonary, and splenic function, and developmental milestones. They will then be randomly assigned to receive either hydroxyurea or placebo and followed yearly to assess chronic end organ damage of the major organ systems. The primary endpoint will be a 50% reduction in rates of damage to the major organs with surrogate markers of organ function during follow-up in Phase II of the trial.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
DOUBLE
Study Groups
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Hydroxyurea
Participants will receive hydroxyurea.
Hydroxyurea
Participants will receive hydroxyurea.
Placebo
Participants will receive placebo.
Placebo
Participants will receive placebo.
Interventions
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Hydroxyurea
Participants will receive hydroxyurea.
Placebo
Participants will receive placebo.
Eligibility Criteria
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Inclusion Criteria
Exclusion Criteria
* Cancer
* Less than 5th percentile (10th percentile for the pilot study) height, weight, or head circumference for age
* Severe developmental delay (e.g., cerebral palsy or other mental retardation, Grade III/IV intraventricular hemorrhage)
* Stroke with neurological deficit
* Surgical splenectomy
* Participating in other clinical intervention trials
* Probable or known diagnosis of Hemoglobin S-Hereditary Persistence of Fetal Hemoglobin
* Known hemoglobin S-beta plus thalassemia (hemoglobin A present)
* Any condition or chronic illness, which in the opinion of the principal investigator, makes participation unadvised or unsafe
* Inability or unwillingness to complete baseline (pre-enrollment) studies, including blood or urine specimen collection, liver-spleen scan, abdominal sonogram, neurological examination, neuropsychological testing, or transcranial Doppler ultrasound (interpretable study not required, but confirmed velocity greater than 200 cm/sec results in ineligibility)
* Previous or current treatment with hydroxyurea (HU) or another anti-sickling drug
1. Hemoglobin less than 6.0 gm/dL
2. Reticulocyte count less than 80,000/cu mm if hemoglobin is less than 9 gm/dL
3. Neutrophil count less than 2,000/cu mm
4. Platelet count less than 130,000/cu mm
5. Blood transfusion in the 2 months prior to study entry unless HbA is less than 10%
6. ALT greater than twice the upper limit of normal
7. Ferritin less than 10 ng/ml
8. Serum creatinine greater than twice the upper limit of normal for age
9. Bayley standardized mental score below 70
9 Months
18 Months
ALL
No
Sponsors
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National Heart, Lung, and Blood Institute (NHLBI)
NIH
Responsible Party
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Principal Investigators
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Sherron Jackson, MD
Role: PRINCIPAL_INVESTIGATOR
Medical University of South Carolina
James F. Casella, MD
Role: PRINCIPAL_INVESTIGATOR
Johns Hopkins University
Lori Luchtman-Jones, MD
Role: PRINCIPAL_INVESTIGATOR
Children's National Research Institute
Rathi V. Iyer, MD
Role: PRINCIPAL_INVESTIGATOR
University of Mississippi Medical Center
Scott T. Miller, MD
Role: PRINCIPAL_INVESTIGATOR
SUNY Health Science Center, Brooklyn
Sohail R. Rana, MD
Role: PRINCIPAL_INVESTIGATOR
Howard University
Zora R. Rogers, MD
Role: PRINCIPAL_INVESTIGATOR
University of Texas SW Medical Center
Bruce W Thompson, Ph.D.
Role: PRINCIPAL_INVESTIGATOR
Clinical Trials and Surveys Corp
Julio Barredo, MD
Role: PRINCIPAL_INVESTIGATOR
University of Miami Medical Center
Winfred C. Wang, MD
Role: STUDY_CHAIR
St. Jude Children's Research Hospital
Courtney Thornburg, MD
Role: PRINCIPAL_INVESTIGATOR
Duke University
Thomas Howard, MD
Role: PRINCIPAL_INVESTIGATOR
University of Alabama at Birmingham
Lori Luck, MD
Role: PRINCIPAL_INVESTIGATOR
Drexel University
R. Clark Brown, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Emory University
Sharada Sarnaik, MD
Role: PRINCIPAL_INVESTIGATOR
Wayne State University
Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Howard University
Washington D.C., District of Columbia, United States
University of Miami
Miami, Florida, United States
Emory University School of Medicine
Atlanta, Georgia, United States
Johns Hopkins University
Baltimore, Maryland, United States
Children's Hospital of Michigan/Wayne State Univ.
Detroit, Michigan, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
SUNY Health Science Center, Brooklyn
Brooklyn, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
Drexel University
Philadelphia, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
University of Texas SW Medical Center
Dallas, Texas, United States
Countries
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References
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Heeney MM, Whorton MR, Howard TA, Johnson CA, Ware RE. Chemical and functional analysis of hydroxyurea oral solutions. J Pediatr Hematol Oncol. 2004 Mar;26(3):179-84. doi: 10.1097/00043426-200403000-00007.
Thompson BW, Miller ST, Rogers ZR, Rees RC, Ware RE, Waclawiw MA, Iyer RV, Casella JF, Luchtman-Jones L, Rana S, Thornburg CD, Kalpatthi RV, Barredo JC, Brown RC, Sarnaik S, Howard TH, Luck L, Wang WC. The pediatric hydroxyurea phase III clinical trial (BABY HUG): challenges of study design. Pediatr Blood Cancer. 2010 Feb;54(2):250-5. doi: 10.1002/pbc.22269.
Wang WC, Ware RE, Miller ST, Iyer RV, Casella JF, Minniti CP, Rana S, Thornburg CD, Rogers ZR, Kalpatthi RV, Barredo JC, Brown RC, Sarnaik SA, Howard TH, Wynn LW, Kutlar A, Armstrong FD, Files BA, Goldsmith JC, Waclawiw MA, Huang X, Thompson BW; BABY HUG investigators. Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet. 2011 May 14;377(9778):1663-72. doi: 10.1016/S0140-6736(11)60355-3.
Wang WC, Pavlakis SG, Helton KJ, McKinstry RC, Casella JF, Adams RJ, Rees RC; BABY HUG Investigators. MRI abnormalities of the brain in one-year-old children with sickle cell anemia. Pediatr Blood Cancer. 2008 Nov;51(5):643-6. doi: 10.1002/pbc.21612.
Miller ST, Wang WC, Iyer R, Rana S, Lane P, Ware RE, Li D, Rees RC; BABY-HUG Investigators. Urine concentrating ability in infants with sickle cell disease: baseline data from the phase III trial of hydroxyurea (BABY HUG). Pediatr Blood Cancer. 2010 Feb;54(2):265-8. doi: 10.1002/pbc.22189.
Pavlakis SG, Rees RC, Huang X, Brown RC, Casella JF, Iyer RV, Kalpatthi R, Luden J, Miller ST, Rogers ZR, Thornburg CD, Wang WC, Adams RJ; BABY HUG Investigators. Transcranial doppler ultrasonography (TCD) in infants with sickle cell anemia: baseline data from the BABY HUG trial. Pediatr Blood Cancer. 2010 Feb;54(2):256-9. doi: 10.1002/pbc.22282.
Thornburg CD, Rogers ZR, Jeng MR, Rana SR, Iyer RV, Faughnan L, Hassen L, Marshall J, McDonald RP, Wang WC, Huang X, Rees RC; BABY HUG Investigators. Adherence to study medication and visits: data from the BABY HUG trial. Pediatr Blood Cancer. 2010 Feb;54(2):260-4. doi: 10.1002/pbc.22324.
Ware RE, Rees RC, Sarnaik SA, Iyer RV, Alvarez OA, Casella JF, Shulkin BL, Shalaby-Rana E, Strife CF, Miller JH, Lane PA, Wang WC, Miller ST; BABY HUG Investigators. Renal function in infants with sickle cell anemia: baseline data from the BABY HUG trial. J Pediatr. 2010 Jan;156(1):66-70.e1. doi: 10.1016/j.jpeds.2009.06.060.
Wynn L, Miller S, Faughnan L, Luo Z, Debenham E, Adix L, Fish B, Hustace T, Kelly T, Macdermott M, Marasciulo J, Martin B, McDuffie J, Murphy M, Rackoff B, Reed C, Seaman P, Thomas G, Wang W. Recruitment of infants with sickle cell anemia to a Phase III trial: data from the BABY HUG study. Contemp Clin Trials. 2010 Nov;31(6):558-63. doi: 10.1016/j.cct.2010.08.007. Epub 2010 Aug 24.
Rogers ZR, Wang WC, Luo Z, Iyer RV, Shalaby-Rana E, Dertinger SD, Shulkin BL, Miller JH, Files B, Lane PA, Thompson BW, Miller ST, Ware RE; BABY HUG. Biomarkers of splenic function in infants with sickle cell anemia: baseline data from the BABY HUG Trial. Blood. 2011 Mar 3;117(9):2614-7. doi: 10.1182/blood-2010-04-278747. Epub 2011 Jan 7.
Wang WC, Oyeku SO, Luo Z, Boulet SL, Miller ST, Casella JF, Fish B, Thompson BW, Grosse SD; BABY HUG Investigators. Hydroxyurea is associated with lower costs of care of young children with sickle cell anemia. Pediatrics. 2013 Oct;132(4):677-83. doi: 10.1542/peds.2013-0333. Epub 2013 Sep 2.
Thornburg CD, Files BA, Luo Z, Miller ST, Kalpatthi R, Iyer R, Seaman P, Lebensburger J, Alvarez O, Thompson B, Ware RE, Wang WC; BABY HUG Investigators. Impact of hydroxyurea on clinical events in the BABY HUG trial. Blood. 2012 Nov 22;120(22):4304-10; quiz 4448. doi: 10.1182/blood-2012-03-419879. Epub 2012 Aug 22.
Alvarez O, Miller ST, Wang WC, Luo Z, McCarville MB, Schwartz GJ, Thompson B, Howard T, Iyer RV, Rana SR, Rogers ZR, Sarnaik SA, Thornburg CD, Ware RE; BABY HUG Investigators. Effect of hydroxyurea treatment on renal function parameters: results from the multi-center placebo-controlled BABY HUG clinical trial for infants with sickle cell anemia. Pediatr Blood Cancer. 2012 Oct;59(4):668-74. doi: 10.1002/pbc.24100. Epub 2012 Jan 31.
Lebensburger JD, Miller ST, Howard TH, Casella JF, Brown RC, Lu M, Iyer RV, Sarnaik S, Rogers ZR, Wang WC; BABY HUG Investigators. Influence of severity of anemia on clinical findings in infants with sickle cell anemia: analyses from the BABY HUG study. Pediatr Blood Cancer. 2012 Oct;59(4):675-8. doi: 10.1002/pbc.24037. Epub 2011 Dec 20.
Miller ST, Rey K, He J, Flanagan J, Fish BJ, Rogers ZR, Wang WC, Ware RE; BABY HUG Investigators. Massive accidental overdose of hydroxyurea in a young child with sickle cell anemia. Pediatr Blood Cancer. 2012 Jul 15;59(1):170-2. doi: 10.1002/pbc.23244. Epub 2011 Jul 8.
McCarville MB, Luo Z, Huang X, Rees RC, Rogers ZR, Miller ST, Thompson B, Kalpatthi R, Wang WC; BABY HUG Investigators. Abdominal ultrasound with scintigraphic and clinical correlates in infants with sickle cell anemia: baseline data from the BABY HUG trial. AJR Am J Roentgenol. 2011 Jun;196(6):1399-404. doi: 10.2214/AJR.10.4664.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form
Other Identifiers
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89
Identifier Type: -
Identifier Source: org_study_id
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