Hydroxyurea to Prevent Stroke in Children With Sickle Cell Anemia and Elevated TCD Flow Velocity
Information source: Duke University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Stroke
Intervention: Hydroxyurea (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Duke University Official(s) and/or principal investigator(s): Sherri Zimmerman, MD, Principal Investigator, Affiliation: Duke University
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.
Clinical Details
Official title: Effects of Hydroxyurea on the Prevention of Primary Stroke in Children With Sickle Cell Anemia and Elevated Transcranial Doppler (TCD) Flow Velocity
Study design: Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Change in TCD flow velocity
Secondary outcome: Stroke
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.
Eligibility
Minimum age: 3 Years.
Maximum age: 18 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Children with Sickle Cell Anemia
- Aged 3 to 18 years
- Confirmed TCD velocity greater than or equal to 140cm/sec
- Negative serum pregnancy test for subjects of childbearing potential
- Decline transfusions (for subjects with TCD velocity greater than or equal to 200
cm/sec)
Locations and Contacts
Duke University Medical Center, Durham, North Carolina 27710, United States
Additional Information
Starting date: April 2003
Last updated: June 17, 2013
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