Pediatric Hydroxyurea in Sickle Cell Anemia (PED HUG)
Condition: Anemia, Sickle Cell; Hematologic Diseases; Hemoglobinopathies
MeSH terms: Anemia; Hematologic Diseases; Hemoglobinopathies; Anemia, Sickle Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      To determine whether hydroxyurea prevents the onset of chronic end organ damage in young
      children with sickle cell anemia.
    

Detailed description: 
      BACKGROUND:

      Sickle cell anemia is a complex syndrome with multiple organ system disturbances brought
      about by the interplay of genetic, humoral, vascular and environmental factors. The clinical
      course can be one of abrupt and insidious exacerbations and remissions, often migratory and
      repetitive. These events may result in impairment of function, permanently damaged organs,
      and ultimately death. Although there is wide variability in the clinical expression of sickle
      cell disease, this complex set of clinical manifestations is experienced by most patients. In
      addition, there is no evidence that the primary disease process is different in children when
      compared with adults with regard to painful episodes. However, children have a higher
      incidence of respiratory viral infections, and are susceptible to pneumococcal septicemia.
      With the successful completion of the Multicenter Study of Hydroxyurea (MSH) Trial in adults,
      attention has now been focused on the use of this agent in children.

      The Cooperative Study of Sickle Cell Disease (CSSCD) has demonstrated that sickle cell anemia
      patients with increased painful episode rates die at a younger age. In addition, increased
      levels of fetal hemoglobin are associated with improved survival, and is probably a reliable
      childhood forecaster of adult life expectancy. The beneficial effect produced by hydroxyurea
      is thought to occur because it increases fetal hemoglobin levels. Therefore, if chronic end
      organ damage can be prevented in early childhood by hydroxyurea administration, and if the
      crisis rate can be decreased by hydroxyurea use early in life, sickle cell anemia patients
      may experience increased longevity and an improved quality of life.

      DESIGN NARRATIVE:

      The Phase I-Phase II study, HUG-KIDS, examined the safety of hydroxyurea. Children with
      sickle cell anemia, age 5 to 15 years, were eligible for this multicenter Phase I/II trial.
      Hydroxyurea was started at 15 mg/kg/d and escalated to 30 mg/kg/d unless the patient
      experienced laboratory toxicity. Patients were monitored by 2-week visits to assess
      compliance, toxicity, clinical adverse events, growth parameters, and laboratory efficacy
      associated with hydroxyurea treatment. Eighty-four children were enrolled between December
      1994 and March 1996. Sixty-eight children reached maximum tolerated dose (MTD) and 52 were
      treated at MTD for 1 year. The study was conducted at four Comprehensive Sickle Cell Centers
      by the following investigators: Thomas R. Kinney at Duke University Medical Center, Durham,
      North Carolina; Kwaku Ohene-Frempong at Children's Hospital of Philadelphia; Orah S. Platt at
      Children's Hospital in Boston; and Elliot Vichinsky at Children's Hospital in Oakland,
      California. The complete study lasted three years.

      The study completion date listed in this record was obtained from the "End Date" entered in
      the Protocol Registration and Results System (PRS) record.
    

Intervention name(s): hydroxyurea
Intervention type(s): Drug
Intervention MeSH terms: Hydroxyurea
Primary purpose: Treatment