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Hematologic DiseasesPhase 3NCT00006400

Hydroxyurea to Prevent Organ Damage in Children With Sickle Cell Anemia

A Phase 3 study testing Hydroxyurea in people with Hematologic Diseases and Anemia, Sickle Cell, run by National Heart, Lung, and Blood Institute (NHLBI) at 14 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 9 to 18 months
Conditions the study is for
Hematologic Diseases, Anemia, Sickle Cell
What is being tested?
Hydroxyurea
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
193 participants
Where
14 sitesUnited States
Study dates
Aug 2000to Sep 2009
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 9 to 18 months
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

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

Who cannot join

  • 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
Show all 22Show fewer
  • 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
  • The following exclusion criteria are transient; patients can be re-evaluated for eligibility:
  • 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
  • Platelet count less than 130,000/cu mm
  • Blood transfusion in the 2 months prior to study entry unless HbA is less than 10%
  • ALT greater than twice the upper limit of normal
  • Ferritin less than 10 ng/ml
  • Serum creatinine greater than twice the upper limit of normal for age
  • Bayley standardized mental score below 70

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites

  • Emory University School of Medicine

    Atlanta, Georgia, 30342

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • SUNY Health Science Center, Brooklyn

    Brooklyn, New York, 11203

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Texas SW Medical Center

    Dallas, Texas, 75390

  • Children's Hospital of Michigan/Wayne State Univ.

    Detroit, Michigan, 48201

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • University of Miami

    Miami, Florida, 33136

  • Drexel University

    Philadelphia, Pennsylvania, 19134

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Howard University

    Washington D.C., District of Columbia, 20060

Other trials in United States

About this study

Official title: Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG)

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.

Read the detailed description

BACKGROUND:

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.

Being tested
Hydroxyurea, Placebo
Keywords
Blood Diseases, Sickle Cell Anemia
Medical subject headings
Hematologic Diseases, Anemia, Sickle Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HydroxyureaDrug

    Participants will receive hydroxyurea.

  • PlaceboDrug

    Participants will receive placebo.

Study groups in NCT00006400
Study groupRoleWhat they receive
HydroxyureaActive comparatorParticipants will receive hydroxyurea.
Receives: Drug: Hydroxyurea
PlaceboPlacebo comparatorParticipants will receive placebo.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Before initiation of treatment and at 2 years

Secondary outcomes (3)

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

    DTPA GFR was originally a co-primary efficacy outcome for the study. Later in May 29, 2009, this measurement was discontinued because of statistical futility (an extremely small chance that the difference between treatment groups would be statistically significant for this outcome) and the small risk posed by the radiation exposure involved with performing the DTPA GFR test. Subjects who had missing data at baseline or 2 years measurement were excluded from the analysis (29 subjects from the hydroxurea, and 31 subjects from the placebo group excluded).

    Measured: Before initiation of treatment and at 2 years

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

    Schwartz formula used to calculate GFR is: 0.55× height (cm)/serum creatinine (mg/dL). Where height is in cm and serum creatinine is in mg/dL. Children with missing baseline or 2 years GFR were excluded from the analysis.

    Measured: Before initiation of treatment and at 2 years

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

    GFR was calculated using new Schwartz formula: 39.1× [height (cm)/serum creatinine (mg/dL)]0.516 × [1.8/cystatin C]0.294 × [30/blood urea nitrogen]0.169 × [1.099]if male × [height(m)/1.4]0.188. Children with missing baseline or 2 years GFR were excluded from the analysis.

    Measured: Before initiation of treatment and at 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Oct 2000 (estimated)
  2. Study startAug 2000
  3. Primary completionSep 2009
  4. Study completionSep 2009

Resources

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 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
193 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00006400
Sponsor's protocol ID
89
Other IDs
N01HB07150, N01HB07151, N01HB07152, N01HB07153, N01HB07154, N01HB07155, N01HB07156, N01HB07157
Status last verified
Apr 2011
First submitted
12 Oct 2000
Last updated
19 Aug 2020
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 15125610

  • 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.

    PubMed 19731330

  • 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.

    PubMed 21571150

  • 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.

    PubMed 18478575

  • 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.

    PubMed 19621454

  • 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.

    PubMed 19813252

  • 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.

    PubMed 19856395

  • 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.

    PubMed 19880138

  • 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.

    PubMed 20797449

  • 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.

    PubMed 21217080

  • 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.

    PubMed 23999955

  • 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.

    PubMed 22915643

  • 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.

    PubMed 22294512

  • 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.

    PubMed 22190441

  • 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.

    PubMed 21744485

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Hydroxyurea in people with Hematologic Diseases and Anemia, Sickle Cell, run by National Heart, Lung, and Blood Institute (NHLBI) at 14 sites 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 1 inclusion and 22 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: finished, as of the sponsor's last update on 19 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Treatment Differences of the Change in Qualitative Splenic Function From Baseline (time frame: Before initiation of treatment and at 2 years). 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 NCT00006400, which also lists 16 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 19 Aug 2020.

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