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Silent Cerebral Infarct Transfusion Multi-Center Clinical Trial (SIT)

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ClinicalTrials.gov Identifier: NCT00072761
Recruitment Status : Completed
First Posted : November 13, 2003
Results First Posted : February 8, 2016
Last Update Posted : February 8, 2016
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Michael DeBaun, Vanderbilt University

Tracking Information
First Submitted Date  ICMJE November 10, 2003
First Posted Date  ICMJE November 13, 2003
Results First Submitted Date  ICMJE May 4, 2015
Results First Posted Date  ICMJE February 8, 2016
Last Update Posted Date February 8, 2016
Study Start Date  ICMJE December 2004
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 7, 2016)
Recurrence of an Infarct, Defined as a Stroke or a New or Enlarged Silent Cerebral Infarct [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00072761 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Silent Cerebral Infarct Transfusion Multi-Center Clinical Trial
Official Title  ICMJE Silent Cerebral Infarct Transfusion Multi-Center Clinical Trial
Brief Summary The goal of this study is to determine the effectiveness of blood transfusion therapy for prevention of silent cerebral infarct (stroke) in children with sickle cell anemia.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Sickle Cell Anemia
  • Stroke
Intervention  ICMJE Procedure: transfusion therapy
Those in the blood transfusion group will receive at least monthly blood transfusion therapy.
Study Arms  ICMJE
  • Active Comparator: Transfusion Group
    Participants allocated to the transfusion arm will receive blood transfusion therapy every 4-6 weeks for 36 months.
    Intervention: Procedure: transfusion therapy
  • No Intervention: 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.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 18, 2012)
196
Original Enrollment  ICMJE
 (submitted: June 23, 2005)
204
Actual Study Completion Date  ICMJE December 2013
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Years to 14 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00072761
Other Study ID Numbers  ICMJE R01NS42804
5U01NS042804-07 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Michael DeBaun, Vanderbilt University
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE National Institute of Neurological Disorders and Stroke (NINDS)
Investigators  ICMJE
Principal Investigator: Michael R. DeBaun, MD, MPH Washington University School of Medicine
PRS Account Washington University School of Medicine
Verification Date January 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP