Stroke occurs in approximately 11% of children with homozygous sickle cell anemia by 20 years of age. Recently, The Stroke Prevention Trial in Sickle Cell Anemia (STOP) showed that high-risk patients can be identified with transcranial Doppler (TCD) ultrasound and that periodic blood transfusions can reduce the annual incidence of first time stroke in high-risk patients from 10% to <1%. Most children in STOP reverted to normal TCD-signifying change to low stroke risk-while on transfusion. The proposed research (STOP II) builds on STOP to optimize the treatment of high- risk patients. Clinical acceptance of this remarkably effective preventive strategy is limited by lack of information on if and when transfusion can be halted after 30 months of treatment in patients who respond to therapy. One hundred children will be randomized over 36 months within 18 months of follow- up after closing recruitment (i.e., 18-54 months of follow-up per patient). Children with evidence of significant arterial disease on Magnetic Resonance Angiography will be excluded. All patients will receive quarterly TCD examinations. A composite endpoint will be used that will consist of reversion to high-risk (TCD (>200 cm/sec) or clinical stroke. Patients who revert to high risk will be offered return to transfusion. TCD, magnetic resonance studies, key laboratory measures and endpoints will be read and/or adjudicated using centralized blinded procedures proved successful in STOP. Assuming the annual endpoint rate on transfusion remains at <1% as seen in STOP, the study will have 90% power to detect an increase to >10% after halting transfusion. This research will optimize the primary prevention strategy proven effective in STOP with significant potential for children with sickle cell anemia.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL052193-08
Application #
6537125
Study Section
Clinical Trials Review Committee (CLTR)
Program Officer
Bonds, Duane
Project Start
1994-07-15
Project End
2005-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
8
Fiscal Year
2002
Total Cost
$2,732,550
Indirect Cost
Name
Medical College of Georgia (MCG)
Department
Neurology
Type
Schools of Medicine
DUNS #
City
Augusta
State
GA
Country
United States
Zip Code
30912
Hyacinth, Hyacinth I; Adams, Robert J; Greenberg, Charles S et al. (2015) Effect of Chronic Blood Transfusion on Biomarkers of Coagulation Activation and Thrombin Generation in Sickle Cell Patients at Risk for Stroke. PLoS One 10:e0134193
Hyacinth, Hyacinth I; Adams, Robert J; Voeks, Jenifer H et al. (2014) Frequent red cell transfusions reduced vascular endothelial activation and thrombogenicity in children with sickle cell anemia and high stroke risk. Am J Hematol 89:47-51
Adams, Robert J (2013) Toward a stroke-free childhood in sickle cell disease: the 2013 Sherman Lecture. Stroke 44:2930-4
Hyacinth, Hyacinth I; Gee, Beatrice E; Adamkiewicz, Thomas V et al. (2012) Plasma BDNF and PDGF-AA levels are associated with high TCD velocity and stroke in children with sickle cell anemia. Cytokine 60:302-8
Abboud, Miguel R; Yim, Eunsil; Musallam, Khaled M et al. (2011) Discontinuing prophylactic transfusions increases the risk of silent brain infarction in children with sickle cell disease: data from STOP II. Blood 118:894-8
Kwiatkowski, Janet L; Yim, Eunsil; Miller, Scott et al. (2011) Effect of transfusion therapy on transcranial Doppler ultrasonography velocities in children with sickle cell disease. Pediatr Blood Cancer 56:777-82
Enninful-Eghan, Henrietta; Moore, ReneƩ H; Ichord, Rebecca et al. (2010) Transcranial Doppler ultrasonography and prophylactic transfusion program is effective in preventing overt stroke in children with sickle cell disease. J Pediatr 157:479-84
Adamkiewicz, Thomas V; Abboud, Miguel R; Paley, Carole et al. (2009) Serum ferritin level changes in children with sickle cell disease on chronic blood transfusion are nonlinear and are associated with iron load and liver injury. Blood 114:4632-8
Brambilla, Donald J; Miller, Scott T; Adams, Robert J (2007) Intra-individual variation in blood flow velocities in cerebral arteries of children with sickle cell disease. Pediatr Blood Cancer 49:318-22
Kirkham, Fenella J; Lerner, Norma B; Noetzel, Michael et al. (2006) Trials in sickle cell disease. Pediatr Neurol 34:450-8

Showing the most recent 10 out of 11 publications