Hydroxyurea to Prevent Stroke in Children With Sickle Cell Anemia and Elevated TCD Flow Velocity
Condition: Stroke
MeSH terms: Stroke; Anemia; Anemia, Sickle Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to assess prospectively the efficacy of hydroxyurea therapy in
      the setting of cerebrovascular disease, manifest as conditional or abnormal transcranial
      doppler ultrasonography (TCD) flow velocities, in children with sickle cell anemia (SCA). TCD
      is used to measure flow velocity in intracranial arteries as a marker of increased stroke
      risk in children with SCA. The primary objective of this protocol is to determine whether
      hydroxyurea reduces elevated TCD velocity.
    

Detailed description: 
      The purpose of this study is to assess prospectively the efficacy of hydroxyurea therapy in
      the setting of cerebrovascular disease, manifest as conditional or abnormal transcranial
      doppler ultrasonography (TCD) flow velocities, in children with sickle cell anemia (SCA). TCD
      is used to measure flow velocity in intracranial arteries as a marker of increased stroke
      risk in children with SCA. The primary objective of this protocol is to determine whether
      hydroxyurea reduces elevated TCD velocity.

      The STOP (Stroke Prevention in Sickle Cell Anemia) trial, a multicenter, randomized,
      controlled trial for primary stroke demonstrated that monthly blood transfusions, when
      compared to observation alone, significantly reduced the risk of primary stroke for children
      with SCA whose TCD velocity exceeded 200 cm/sec. Despite the STOP trial's clear results,
      there are unresolved issues regarding TCD and stroke risk in children with SCA. First, the
      predictive value of an abnormal result is not compelling since less than a third of children
      with an abnormal TCD velocity and even fewer with conditional results will ever develop a
      clinical stroke. There is also discordance between TCD and MRI results. Only 40% of children
      with abnormal TCD velocity will have abnormalities on brain MRI (Wang, et al. J Pediatr
      Hematol/Oncol 2000;22(4):335-339, Pegelow, et al. Arch Neurol 2001;58:2017-2021). There are
      also well recognized risks of chronic blood transfusions, including iron overload and
      alloimmunization, and the necessary duration of transfusion protection for children with
      abnormal TCD velocity is unknown. Unfortunately, there are currently no therapeutic options
      besides blood transfusions for patients with SCA and an abnormal TCD velocity.

      Erythrocyte transfusions and hydroxyurea have many similar beneficial effects in patients
      with SCA. Transfusions may prevent primary stroke by lowering the % HbS, by increasing the
      hematocrit, by improving red cell rheology, by decreasing red cell adhesion, and by lowering
      TCD velocity. Hydroxyurea leads to many of the same changes, thus in this protocol, we will
      examine whether hydroxyurea, like transfusions, can lower TCD velocity. In our patients with
      SCA who have been screened with TCD ultrasonography, we have observed that children who were
      screened while receiving hydroxyurea had lower TCD velocity measurements than those who were
      not on hydroxyurea. In a small number of patients with TCD velocity measurements before and
      after initiation of hydroxyurea for non-neurological reasons, the TCD velocity declined
      significantly after achieving full dose hydroxyurea therapy. The changes in TCD velocity were
      correlated with changes in hematocrit since hydroxyurea increases blood counts in patients
      with SCA. For each % increase in hematocrit, the TCD velocity increased by 6.3 cm/sec. This
      was similar to an abstract from the STOP trial, in which TCD flow velocity declined by 7.9
      cm/sec for each increase in % hematocrit from transfusions.

      Based on this preliminary data, we initiated this prospective, single-institution, pilot
      trial to determine whether hydroxyurea therapy lowers TCD flow velocity in children with
      sickle cell anemia.
    

Intervention name(s): Hydroxyurea
Intervention type(s): Drug
Intervention MeSH terms: Hydroxyurea
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Sickle Cell Anemia with Elevated TCD flow velocity