- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00072761
Silent Cerebral Infarct Transfusion Multi-Center Clinical Trial (SIT)
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Silent cerebral infarct (stroke) is the most common cause of severe cognitive impairments and related neurological functions in children with sickle cell anemia. Currently there exists no systemic strategy to identify or treat children with silent strokes.
The primary aim of this trial is to determine the effectiveness of blood transfusion therapy for the prevention of silent strokes in children with sickle cell anemia. This trial will also determine if blood transfusion therapy will prevent further cerebral injury and if the measured benefits of the therapy outweigh the risks associated with it.
Participants in this multi-center trial will be randomly assigned to one of 2 groups-the blood transfusion group or the observation group. Those in the blood transfusion group will receive at least monthly blood transfusion therapy. All participants will have history and physical examinations every 3 months, and magnetic resonance imaging (MRI) at the beginning of their entry into the study and at study exit.
Advances in the understanding and treatment of silent strokes will likely lead to a decrease in the burden associated with cerebral injury in children with sickle cell anemia and change the standard care for these children.
Statistical Analyses: The original statistical analysis plan suggested a simple difference in proportions between the proportion of individuals with an endpoint in the transfusion group and the proportion of individuals with an endpoint in the usual care group using a traditional chi squared test. The data should be analyzed according to an intent to treat principal. Because of various logistical concerns in SIT, some individuals were not imaged within the 36-month window (30-42 months). We propose using all available information by changing the primary analysis from a dichotomous (yes/no) endpoint to a traditional epidemiological endpoint of an incidence rate in the group randomized to transfusion to the incidence rate in the group randomized to usual care. We will compute the incidence ratio:
(a/ta)/(b/tb)
Where "a" is the number of endpoints in the transfusion group, "ta" is the sum of the individual times at risk of the individuals randomized to the transfusion group, "b" is the number of endpoints in the observation group and "tb" is the sum of the individual times at risk of the individuals randomized to the observation group.
Since the standard statistical test for it being different than 1.0 involves the assumption of a Poisson distribution, we will compute an "exact" 95% confidence interval using a bootstrap with a large number of replications.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 3
Contactos y Ubicaciones
Ubicaciones de estudio
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Missouri
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St. Louis, Missouri, Estados Unidos, 63110
- Washington University School of Medicine
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
INCLUSION:
- Patient must have sickle cell anemia (hemoglobin SS) or sickle beta thalassemia (hemoglobin SB) as confirmed at the local institution.
- Participating institutions must submit documentation of the diagnostic hemoglobin analysis to the Statistical and Clinical Coordinating Centers to confirm the diagnosis of sickle cell anemia prior to randomization.
- Patient must be 5 through 14 years of age.
- Patient must have a cerebral infarct documented by MRI scan as read by the neuroradiology panel.
- Informed consent with assent in accordance with the institutional policies (institutional Institutional Review Board approval) and Federal guidelines (approved by the United States Department of Health and Human Services) must be signed by the patient's legally authorized guardian acknowledging written consent to join the study. When suitable, patients will be requested to give their assent to join the study.
EXCLUSION:
- Patient with a history of a focal neurologic event lasting more than 24 hours with medical documentation or a history of prior overt stroke.
- Patients with a transcranial doppler (TCD) study with a time-averaged mean velocity greater than 200 cm/sec verified by the study radiologist.
- Patients with other neurological problems, such as neurofibromatosis, lead poisoning, or tuberous sclerosis.
- Patients with HIV infection.
- Pregnancy.
- Patients who received treatment with anti-sickling drugs or hydroxyurea within 3 months or anticipate receiving anti-sickling drugs or hydroxyurea during the course of the study.
- Abnormal kidney function (creatinine > 2x upper limit of normal).
- Patients on chronic blood transfusion therapy for other reasons.
- Patients judged not likely to be compliant by his/her hematologist and local nurse coordinator based on previous compliance in clinic appointments and following advice. Specifically, families that have missed at least two appointments without notification within 12 months prior to the trial or parents of potential patients that have been reported for medical or education neglect are not eligible for this trial.
- Patients unable to receive blood transfusion because of alloimmunization.
- Patients with permanent or semi-permanent metallic (braces on teeth) structures attached to their body. Such patients cannot obtain a MRI of the head to assess the presence of silent cerebral infarcts.
- Siblings randomized in the trial.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Único
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Comparador activo: Transfusion Group
Participants allocated to the transfusion arm will receive blood transfusion therapy every 4-6 weeks for 36 months.
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Those in the blood transfusion group will receive at least monthly blood transfusion therapy.
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Sin intervención: Observation Group
Participants allocated to the observation arm will be treated according to standard care and will receive a quarterly physical examination by a study hematologist for 36 months.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Recurrence of an Infarct, Defined as a Stroke or a New or Enlarged Silent Cerebral Infarct
Periodo de tiempo: From study entry to study exit
|
The primary end point was the recurrence of infarct or hemorrhage as determined by neuroimaging, clinical evidence of permanent neurologic injury, or both.
A new infarct had to meet the criteria for a silent cerebral infarction; an enlarged silent cerebral infarct was defined as a previously identified silent cerebral infarct that increased by at least 3 mm along any linear dimension in any plane on MRI.
|
From study entry to study exit
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Michael R. DeBaun, MD, MPH, Washington University School of Medicine
Publicaciones y enlaces útiles
Publicaciones Generales
- Milton JN, Sebastiani P, Solovieff N, Hartley SW, Bhatnagar P, Arking DE, Dworkis DA, Casella JF, Barron-Casella E, Bean CJ, Hooper WC, DeBaun MR, Garrett ME, Soldano K, Telen MJ, Ashley-Koch A, Gladwin MT, Baldwin CT, Steinberg MH, Klings ES. A genome-wide association study of total bilirubin and cholelithiasis risk in sickle cell anemia. PLoS One. 2012;7(4):e34741. doi: 10.1371/journal.pone.0034741. Epub 2012 Apr 27.
- Casella JF, King AA, Barton B, White DA, Noetzel MJ, Ichord RN, Terrill C, Hirtz D, McKinstry RC, Strouse JJ, Howard TH, Coates TD, Minniti CP, Campbell AD, Vendt BA, Lehmann H, Debaun MR. Design of the silent cerebral infarct transfusion (SIT) trial. Pediatr Hematol Oncol. 2010 Mar;27(2):69-89. doi: 10.3109/08880010903360367.
- Buchanan GR, DeBaun MR, Quinn CT, Steinberg MH. Sickle cell disease. Hematology Am Soc Hematol Educ Program. 2004:35-47. doi: 10.1182/asheducation-2004.1.35.
- Vendt BA, McKinstry RC, Ball WS, Kraut MA, Prior FW, Barton B, Casella JF, DeBaun MR. Silent Cerebral Infarct Transfusion (SIT) trial imaging core: application of novel imaging information technology for rapid and central review of MRI of the brain. J Digit Imaging. 2009 Jun;22(3):326-43. doi: 10.1007/s10278-008-9114-3. Epub 2008 Apr 9.
- Jordan LC, McKinstry RC 3rd, Kraut MA, Ball WS, Vendt BA, Casella JF, DeBaun MR, Strouse JJ; Silent Infarct Transfusion Trial Investigators. Incidental findings on brain magnetic resonance imaging of children with sickle cell disease. Pediatrics. 2010 Jul;126(1):53-61. doi: 10.1542/peds.2009-2800. Epub 2010 Jun 14.
- Bhatnagar P, Purvis S, Barron-Casella E, DeBaun MR, Casella JF, Arking DE, Keefer JR. Genome-wide association study identifies genetic variants influencing F-cell levels in sickle-cell patients. J Hum Genet. 2011 Apr;56(4):316-23. doi: 10.1038/jhg.2011.12. Epub 2011 Feb 17.
- Jordan LC, Casella JF, DeBaun MR. Prospects for primary stroke prevention in children with sickle cell anaemia. Br J Haematol. 2012 Apr;157(1):14-25. doi: 10.1111/j.1365-2141.2011.09005.x. Epub 2012 Jan 9.
- DeBaun MR, Sarnaik SA, Rodeghier MJ, Minniti CP, Howard TH, Iyer RV, Inusa B, Telfer PT, Kirby-Allen M, Quinn CT, Bernaudin F, Airewele G, Woods GM, Panepinto JA, Fuh B, Kwiatkowski JK, King AA, Rhodes MM, Thompson AA, Heiny ME, Redding-Lallinger RC, Kirkham FJ, Sabio H, Gonzalez CE, Saccente SL, Kalinyak KA, Strouse JJ, Fixler JM, Gordon MO, Miller JP, Noetzel MJ, Ichord RN, Casella JF. Associated risk factors for silent cerebral infarcts in sickle cell anemia: low baseline hemoglobin, sex, and relative high systolic blood pressure. Blood. 2012 Apr 19;119(16):3684-90. doi: 10.1182/blood-2011-05-349621. Epub 2011 Nov 17.
- Thangarajh M, Yang G, Fuchs D, Ponisio MR, McKinstry RC, Jaju A, Noetzel MJ, Casella JF, Barron-Casella E, Hooper WC, Boulet SL, Bean CJ, Pyle ME, Payne AB, Driggers J, Trau HA, Vendt BA, Rodeghier M, DeBaun MR. Magnetic resonance angiography-defined intracranial vasculopathy is associated with silent cerebral infarcts and glucose-6-phosphate dehydrogenase mutation in children with sickle cell anaemia. Br J Haematol. 2012 Nov;159(3):352-9. doi: 10.1111/bjh.12034. Epub 2012 Sep 7.
- Quinn CT, McKinstry RC, Dowling MM, Ball WS, Kraut MA, Casella JF, Dlamini N, Ichord RN, Jordan LC, Kirkham FJ, Noetzel MJ, Roach ES, Strouse JJ, Kwiatkowski JL, Hirtz D, DeBaun MR. Acute silent cerebral ischemic events in children with sickle cell anemia. JAMA Neurol. 2013 Jan;70(1):58-65. doi: 10.1001/jamaneurol.2013.576.
- Bean CJ, Boulet SL, Ellingsen D, Pyle ME, Barron-Casella EA, Casella JF, Payne AB, Driggers J, Trau HA, Yang G, Jones K, Ofori-Acquah SF, Hooper WC, DeBaun MR. Heme oxygenase-1 gene promoter polymorphism is associated with reduced incidence of acute chest syndrome among children with sickle cell disease. Blood. 2012 Nov 1;120(18):3822-8. doi: 10.1182/blood-2011-06-361642. Epub 2012 Sep 10.
- DeBaun MR, Armstrong FD, McKinstry RC, Ware RE, Vichinsky E, Kirkham FJ. Silent cerebral infarcts: a review on a prevalent and progressive cause of neurologic injury in sickle cell anemia. Blood. 2012 May 17;119(20):4587-96. doi: 10.1182/blood-2011-02-272682. Epub 2012 Feb 21.
- Glassberg JA, Wang J, Cohen R, Richardson LD, DeBaun MR. Risk factors for increased ED utilization in a multinational cohort of children with sickle cell disease. Acad Emerg Med. 2012 Jun;19(6):664-72. doi: 10.1111/j.1553-2712.2012.01364.x.
- An P, Barron-Casella EA, Strunk RC, Hamilton RG, Casella JF, DeBaun MR. Elevation of IgE in children with sickle cell disease is associated with doctor diagnosis of asthma and increased morbidity. J Allergy Clin Immunol. 2011 Jun;127(6):1440-6. doi: 10.1016/j.jaci.2010.12.1114. Epub 2011 Mar 9.
- DeBaun MR, Gordon M, McKinstry RC, Noetzel MJ, White DA, Sarnaik SA, Meier ER, Howard TH, Majumdar S, Inusa BP, Telfer PT, Kirby-Allen M, McCavit TL, Kamdem A, Airewele G, Woods GM, Berman B, Panepinto JA, Fuh BR, Kwiatkowski JL, King AA, Fixler JM, Rhodes MM, Thompson AA, Heiny ME, Redding-Lallinger RC, Kirkham FJ, Dixon N, Gonzalez CE, Kalinyak KA, Quinn CT, Strouse JJ, Miller JP, Lehmann H, Kraut MA, Ball WS Jr, Hirtz D, Casella JF. Controlled trial of transfusions for silent cerebral infarcts in sickle cell anemia. N Engl J Med. 2014 Aug 21;371(8):699-710. doi: 10.1056/NEJMoa1401731.
- Hsu P, Gay JC, Lin CJ, Rodeghier M, DeBaun MR, Cronin RM. Economic evaluation of regular transfusions for cerebral infarct recurrence in the Silent Cerebral Infarct Transfusion Trial. Blood Adv. 2021 Dec 14;5(23):5032-5040. doi: 10.1182/bloodadvances.2021004864.
- Dowling MM, Noetzel MJ, Rodeghier MJ, Quinn CT, Hirtz DG, Ichord RN, Kwiatkowski JL, Roach ES, Kirkham FJ, Casella JF, DeBaun MR. Headache and migraine in children with sickle cell disease are associated with lower hemoglobin and higher pain event rates but not silent cerebral infarction. J Pediatr. 2014 May;164(5):1175-1180.e1. doi: 10.1016/j.jpeds.2014.01.001. Epub 2014 Feb 13.
- Savage WJ, Barron-Casella E, Fu Z, Dulloor P, Williams L, Crain BJ, White DA, Jennings JM, Van Eyk JE, Debaun MR, Everett A, Casella JF. Plasma glial fibrillary acidic protein levels in children with sickle cell disease. Am J Hematol. 2011 May;86(5):427-9. doi: 10.1002/ajh.21995.
- Williams LM, Fu Z, Dulloor P, Yen T, Barron-Casella E, Savage W, Van Eyk JE, Casella JF, Everett A. Hemoglobin depletion from plasma: considerations for proteomic discovery in sickle cell disease and other hemolytic processes. Proteomics Clin Appl. 2010 Dec;4(12):926-30. doi: 10.1002/prca.201000054.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Isquemia
- Procesos Patológicos
- Necrosis
- Enfermedades cardiovasculares
- Enfermedades Vasculares
- Trastornos cerebrovasculares
- Enfermedades Cerebrales
- Enfermedades del Sistema Nervioso Central
- Enfermedades del Sistema Nervioso
- Enfermedades hematológicas
- Enfermedades Genéticas Congénitas
- Anemia
- Isquemia cerebral
- Carrera
- Infarto cerebral
- Anemia Hemolítica Congénita
- Anemia Hemolítica
- Hemoglobinopatías
- Infarto
- Infarto cerebral
- Anemia de células falciformes
Otros números de identificación del estudio
- R01NS42804
- 5U01NS042804-07 (Subvención/contrato del NIH de EE. UU.)
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
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