Hydroxyurea to Prevent Organ Damage in Children With Sickle Cell Anemia

NCT00006400 | Completed Phase 3 Results DMC

• 12 other identifiers: 89N01HB07150N01HB07151N01HB07152N01HB07153N01HB07154N01HB07155N01HB07156N01HB07157N01HB07158N01HB07159N01HB07160
• Study Type: interventional
• Target: 193
• Locations: 1 country
• Sites: 14

Brief Summary

The purpose of this study is to determine if hydroxyurea therapy is effective in the prevention of chronic end organ damage in pediatric patients with sickle cell anemia.

Conditions

Hematologic Diseases; Anemia, Sickle Cell

Keywords

Blood Diseases; Sickle Cell Anemia

Outcome Measures

Primary Outcomes (1)

• Treatment Differences of the Change in Qualitative Splenic Function From Baseline

  Primary Endpoint: Spleen function was assessed by uptake of 99mTc sulfur colloid on liver-spleen scan before initiation of treatment (baseline) and 2 years later (exit). The results of each of the two scans were categorized as normal, functional but abnormal, or not functional by a panel of nuclear medicine specialists blinded to treatment assignment. The proportion of patients whose paired scans demonstrated a decline in splenic function was compared in the hydroxyurea versus placebo groups. The change in splenic function from baseline to 2 years was defined as worse if it changed from normal to decreased or absent, or decreased to absent; and not worse if it changed from decreased to decreased, normal to normal, or decreased to normal.

  Before initiation of treatment and at 2 years

Secondary Outcomes (3)

• Change From Baseline in the Renal Function That Was Measured by Diethylenetriaminepentaacetic Acid (DTPA) Glomerular Filtration Rate (GFR)

  Before initiation of treatment and at 2 years

• Change From Baseline in the Renal Function That Was Measured by Glomerular Filtration Rate (GFR) (Calculated Using Schwartz Formula)

  Before initiation of treatment and at 2 years

• Change From Baseline in the Renal Function That Was Measured by GFR (Calculated Using New Schwartz Formula)

  Before initiation of treatment and at 2 years

Study Arms (2)

Hydroxyurea

ACTIVE COMPARATOR

Participants will receive hydroxyurea.

Drug: Hydroxyurea

Placebo

PLACEBO COMPARATOR

Participants will receive placebo.

Drug: Placebo

Interventions

Hydroxyurea DRUG

Participants will receive hydroxyurea.

Hydroxyurea

Placebo DRUG

Participants will receive placebo.

Placebo

Eligibility Criteria

• Age: 9 Months - 18 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Majority fetal and sickle (FS or SF) hemoglobin pattern confirmed centrally by electrophoresis (screening may begin at 7 months of age)

You may not qualify if:

• Chronic transfusion therapy
• 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
• Hemoglobin less than 6.0 gm/dL
• Reticulocyte count less than 80,000/cu mm if hemoglobin is less than 9 gm/dL
• Neutrophil count less than 2,000/cu mm

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (14)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Howard University

Washington D.C., District of Columbia, 20060, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30342, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Children's Hospital of Michigan/Wayne State Univ.

Detroit, Michigan, 48201, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

SUNY Health Science Center, Brooklyn

Brooklyn, New York, 11203, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Drexel University

Philadelphia, Pennsylvania, 19134, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

University of Texas SW Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (16)

• 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.

  PMID: 15125610 BACKGROUND

• 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.

  PMID: 19731330 BACKGROUND

• 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.

  PMID: 21571150 RESULT

• 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.

  PMID: 18478575 RESULT

• 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.

  PMID: 19621454 RESULT

• 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.

  PMID: 19813252 RESULT

• 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.

  PMID: 19856395 RESULT

• 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.

  PMID: 19880138 RESULT

• 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.

  PMID: 20797449 RESULT

• 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.

  PMID: 21217080 RESULT

• 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.

  PMID: 23999955 DERIVED

• 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.

  PMID: 22915643 DERIVED

• 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.

  PMID: 22294512 DERIVED

• 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.

  PMID: 22190441 DERIVED

• 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.

  PMID: 21744485 DERIVED

• 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.

  PMID: 21606305 DERIVED

MeSH Terms

Conditions

Hematologic Diseases; Anemia, Sickle Cell

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Results Point of Contact

• Title: Julie Miller
• Organization: New England Research Institutes, Inc

JMiller@healthcore.com

617-972-3197

Study Officials

• Sherron Jackson, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

• James F. Casella, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Lori Luchtman-Jones, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

• Rathi V. Iyer, MD

  University of Mississippi Medical Center

  PRINCIPAL INVESTIGATOR

• Scott T. Miller, MD

  SUNY Health Science Center, Brooklyn

  PRINCIPAL INVESTIGATOR

• Sohail R. Rana, MD

  Howard University

  PRINCIPAL INVESTIGATOR

• Zora R. Rogers, MD

  University of Texas SW Medical Center

  PRINCIPAL INVESTIGATOR

• Bruce W Thompson, Ph.D.

  Clinical Trials and Surveys Corp

  PRINCIPAL INVESTIGATOR

• Julio Barredo, MD

  University of Miami Medical Center

  PRINCIPAL INVESTIGATOR

• Winfred C. Wang, MD

  St. Jude Children's Research Hospital

  STUDY CHAIR

• Courtney Thornburg, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• Thomas Howard, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Lori Luck, MD

  Drexel University

  PRINCIPAL INVESTIGATOR

• R. Clark Brown, MD, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

• Sharada Sarnaik, MD

  Wayne State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2000
• First Posted: October 13, 2000
• Study Start: August 1, 2000
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: August 19, 2020
• Results First Posted: August 19, 2020

Record last verified: 2011-04

Locations

US (14)