Stroke Prevention Trial in Sickle Cell Anemia

Robert J. Adams, Virgil C. McKie, Don Brambilla, Elizabeth Carl, Dianne Gallagher, Fenwick T Nichols, Steve Roach, Miguel Abboud, Brian Berman, Catherine Driscoll, Beatrice Files, Lewis Hsu, Anne Hurlet, Scott Miller, Nancy Olivieri, Charles Pegelow, Charles Scher, Elliott Vichinsky, Winfred Wang, Gerald Woods & 8 others Abdullah Kutlar, Elizabeth Wright, Susan Hagner, Foss Tighe, Jonathan Lewin, Joel Cure, Robert A. Zimmerman, Myron A. Waclawiw

Research output: Contribution to journalArticle

168 Citations (Scopus)

Abstract

Stroke occurs in 7-8% of children with Sickle Cell Disease (Hb SS) and is a major cause of morbidity. Rates of recurrence have been reduced from 46-90% to less than 10% through chronic blood transfusions. Prevention of first stroke, however, would be preferable because even one stroke can cause irreversible brain injury. Transcranial Doppler (TCD) ultrasound can detect arterial blood flow rates associated with subsequent stroke risk. By combining TCD screening and a potentially effective treatment, first stroke may be prevented. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) is the first stroke prevention trial in Hb SS and the first randomized, controlled use of transfusion in Hb SS. This multi-center trial is designed to test whether reducing sickle hemoglobin to 30% or less with periodic blood transfusions will reduce first-time stroke by at least 70% compared to standard care. Primary endpoints will be clinically evident symptoms of cerebral infarction with consistent findings on Magnetic Resonance Imaging and Angiography (MRI/MRA) or symptomatic intracranial hemorrhage. Secondary endpoints will be asymptomatic brain lesions detected by MRI in brain areas not involved in primary endpoints. The design calls for a 6-month start-up interval, 18 months of TCD screening and randomization, and observation for stroke from entry through month 54. Key features of the trial are standardized TCD and MRI/MRA protocols interpreted blindly, and blinded adjudication of endpoints. The sample size (60 per treatment group) is based on prospective data relating TCD velocity to risk of stroke. A time-averaged mean velocity of ≤ 200 cm/sec is associated with a 46% risk of cerebral infarction over 39 months. The sample size is sufficient to detect 70% reduction in the primary endpoint at 90% power. This trial will determine if transfusion is effective in the primary prevention of stroke. Secondary aims may further the understanding of the effects of transfusion on the brain and guide future research into cerebrovascular disease in Hb SS.

Original languageEnglish (US)
Pages (from-to)110-129
Number of pages20
JournalControlled Clinical Trials
Volume19
Issue number1
DOIs
StatePublished - Jan 1 1998

Fingerprint

Sickle Cell Anemia
Stroke
Magnetic Resonance Angiography
Cerebral Infarction
Blood Transfusion
Sample Size
Brain
Magnetic Resonance Imaging
Sickle Hemoglobin
Cerebrovascular Disorders
Doppler Ultrasonography
Intracranial Hemorrhages
Primary Prevention
Random Allocation
Brain Injuries
Observation
Morbidity
Recurrence

Keywords

  • Cerebral hemorrhage
  • Cerebral infarction
  • Children/pediatric
  • Magnetic Resonance Angiography
  • Magnetic Resonance Imaging
  • Randomized controlled trial
  • Sickle Cell Disease
  • Stroke
  • Transcranial Doppler ultrasound
  • Transfusion

ASJC Scopus subject areas

  • Pharmacology

Cite this

Adams, R. J., McKie, V. C., Brambilla, D., Carl, E., Gallagher, D., Nichols, F. T., ... Waclawiw, M. A. (1998). Stroke Prevention Trial in Sickle Cell Anemia. Controlled Clinical Trials, 19(1), 110-129. https://doi.org/10.1016/S0197-2456(97)00099-8

Stroke Prevention Trial in Sickle Cell Anemia. / Adams, Robert J.; McKie, Virgil C.; Brambilla, Don; Carl, Elizabeth; Gallagher, Dianne; Nichols, Fenwick T; Roach, Steve; Abboud, Miguel; Berman, Brian; Driscoll, Catherine; Files, Beatrice; Hsu, Lewis; Hurlet, Anne; Miller, Scott; Olivieri, Nancy; Pegelow, Charles; Scher, Charles; Vichinsky, Elliott; Wang, Winfred; Woods, Gerald; Kutlar, Abdullah; Wright, Elizabeth; Hagner, Susan; Tighe, Foss; Lewin, Jonathan; Cure, Joel; Zimmerman, Robert A.; Waclawiw, Myron A.

In: Controlled Clinical Trials, Vol. 19, No. 1, 01.01.1998, p. 110-129.

Research output: Contribution to journalArticle

Adams, RJ, McKie, VC, Brambilla, D, Carl, E, Gallagher, D, Nichols, FT, Roach, S, Abboud, M, Berman, B, Driscoll, C, Files, B, Hsu, L, Hurlet, A, Miller, S, Olivieri, N, Pegelow, C, Scher, C, Vichinsky, E, Wang, W, Woods, G, Kutlar, A, Wright, E, Hagner, S, Tighe, F, Lewin, J, Cure, J, Zimmerman, RA & Waclawiw, MA 1998, 'Stroke Prevention Trial in Sickle Cell Anemia', Controlled Clinical Trials, vol. 19, no. 1, pp. 110-129. https://doi.org/10.1016/S0197-2456(97)00099-8
Adams RJ, McKie VC, Brambilla D, Carl E, Gallagher D, Nichols FT et al. Stroke Prevention Trial in Sickle Cell Anemia. Controlled Clinical Trials. 1998 Jan 1;19(1):110-129. https://doi.org/10.1016/S0197-2456(97)00099-8
Adams, Robert J. ; McKie, Virgil C. ; Brambilla, Don ; Carl, Elizabeth ; Gallagher, Dianne ; Nichols, Fenwick T ; Roach, Steve ; Abboud, Miguel ; Berman, Brian ; Driscoll, Catherine ; Files, Beatrice ; Hsu, Lewis ; Hurlet, Anne ; Miller, Scott ; Olivieri, Nancy ; Pegelow, Charles ; Scher, Charles ; Vichinsky, Elliott ; Wang, Winfred ; Woods, Gerald ; Kutlar, Abdullah ; Wright, Elizabeth ; Hagner, Susan ; Tighe, Foss ; Lewin, Jonathan ; Cure, Joel ; Zimmerman, Robert A. ; Waclawiw, Myron A. / Stroke Prevention Trial in Sickle Cell Anemia. In: Controlled Clinical Trials. 1998 ; Vol. 19, No. 1. pp. 110-129.
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AU - Nichols, Fenwick T

AU - Roach, Steve

AU - Abboud, Miguel

AU - Berman, Brian

AU - Driscoll, Catherine

AU - Files, Beatrice

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