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SACRED A Prospective Research Study to Reduce Stroke in Children With Sickle Cell Anemia (SACRED)

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ClinicalTrials.gov Identifier: NCT02769845
Recruitment Status : Recruiting
First Posted : May 12, 2016
Last Update Posted : August 30, 2017
Sponsor:
Collaborator:
Hospital Infantil Dr. Robert Reid Cabral
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Brief Summary:
Prospective screening and treatment study for children with Sickle Cell Anemia and increased stroke risk living in the Dominican Republic.

Condition or disease Intervention/treatment Phase
Sickle Cell Anemia Drug: Hydroxyurea Procedure: TCD examination Not Applicable

Detailed Description:

SACRED involves a three-part study design, as outlined below, to include (1) initial TCD evaluation phase; (2) longitudinal TCD evaluation; and (3) treatment if warranted.

  1. The initial evaluation portion of SACRED will involve obtaining TCD examinations on children with SCA between ages 3-15 years, who are followed at Hospital Infantil Robert Reid Cabral in Santo Domingo to evaluate their risk of stroke. Up to 500 patients will be enrolled. All patients, including those who are already on hydroxyurea and transfusion therapy (whether for stroke or other clinical indications), will be included to obtain a one-year cross-sectional description of TCD velocities in this patient population. Patients who are already on therapy and identified to have elevated TCD velocities will be eligible for the treatment portion of SACRED as a conditional or elevated velocity would suggest that their present therapy was not optimized.
  2. In the longitudinal portion of SACRED, all enrolled children will undergo yearly TCD examination. The goal of serial examination is to help define the natural history of cerebrovascular disease, specifically to determine the incidence of new conditional or abnormal velocities. The goal is to obtain a total of 3 TCD examinations per enrolled patient, regardless of treatment status.
  3. In the treatment phase of SACRED, those children with TCD velocities between 170-199 cm/sec will be eligible for protocol-directed hydroxyurea therapy. Most participants will initiate hydroxyurea treatment but those who are already on hydroxyurea and have conditional velocities will receive dose optimization. Participants will be followed until a common study termination date, defined as 3 years from the first treatment. Participants with abnormal TCD velocities ≥200 cm/sec will commence with transfusion therapy per current practice guidelines at the clinical site. Patients already on transfusion therapy identified to have conditional velocities will also be eligible for hydroxyurea and those with abnormal velocities may require re-calculation of transfusion dosing.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Stroke Avoidance for Children in REpublica Dominicana (SACRED): A Prospective Research Study to Reduce Stroke in Children With Sickle Cell Anemia
Study Start Date : May 2016
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia
Drug Information available for: Hydroxyurea

Arm Intervention/treatment
Experimental: Longitudinal Portion
All enrolled children will undergo yearly TCD examination. The goal of serial examination is to help define the natural history of cerebrovascular disease, specifically to determine the incidence of new conditional or abnormal velocities. The goal is to obtain a total of 3 TCD examinations per enrolled patient, regardless of treatment status.
Procedure: TCD examination
TCD examinations on children with SCA between ages 3-15 years will be completed to evaluate their risk of stroke. All enrolled children will undergo yearly TCD examination. Participants with conditional TCD velocities on hydroxyurea therapy per study protocol will undergo TCD examinations every 6 months.

Experimental: Treatment Phase
Those children with TCD velocities between 170-199 cm/sec will be eligible for protocol-directed hydroxyurea therapy. Most participants will initiate hydroxyurea treatment but those who are already on hydroxyurea and have conditional velocities will receive dose optimization. Participants will be followed until a common study termination date, defined as 3 years from the first treatment. Participants with abnormal TCD velocities ≥200 cm/sec will commence with transfusion therapy per current practice guidelines at the clinical site. Patients already on transfusion therapy identified to have conditional velocities will also be eligible for hydroxyurea and those with abnormal velocities may require re-calculation of transfusion dosing.
Drug: Hydroxyurea
drug to be administered

Procedure: TCD examination
TCD examinations on children with SCA between ages 3-15 years will be completed to evaluate their risk of stroke. All enrolled children will undergo yearly TCD examination. Participants with conditional TCD velocities on hydroxyurea therapy per study protocol will undergo TCD examinations every 6 months.




Primary Outcome Measures :
  1. Transcranial Doppler Ultrasound examinations [ Time Frame: 0-24 months ]
    Serial TCD velocities will be measured yearly for participants not receiving hydroxyurea and every six months for participants receiving hydroxyurea during the trial. The outcome measure will be the highest TAMV obtained in the main intracranial arteries: middle cerebral artery (MCA), internal carotid artery (ICA), or internal carotid bifurcation (BIF). Subsequent TCD velocities will be compared to the baseline TCD values to describe the potential efficacy of hydroxyurea to reduce elevated TCD velocities.


Secondary Outcome Measures :
  1. Hydroxyurea toxicities [ Time Frame: 0-30 months ]
    This measure will be performed at least quarterly throughout the trial, and monthly during dose escalation by recording the CBC and Retic count.



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Ages Eligible for Study:   3 Years to 15 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pediatric participants with severe forms of sickle cell anemia (HbSS or HbSβ° thalassemia)
  • Age: between 3.0 and 15.0 years at the time of enrollment
  • Parent or guardian willing and able to provide informed consent
  • Ability to comply with study related treatments, evaluations, and follow-up

There are no exclusion criteria applicable to the TCD screening portion of SACRED.

For participants with conditional TCD velocities, the following criteria will disqualify them from the treatment phase of SACRED:

Exclusion Criteria:

  • Known medical condition making participation ill-advised (e.g., acute or chronic infectious disease including HIV, known allergy to hydroxyurea therapy, or malignancy)
  • Abnormal historical laboratory values (most recent pre-enrollment values):

    1. Anemia: Hemoglobin concentration < 6.0 gm/dL
    2. Reticulocytopenia: Absolute reticulocyte count < 100 x 109/L with a hemoglobin concentration < 8.0 gm/dL
    3. Neutropenia: Absolute neutrophil count (ANC) < 1.0 x 109/L
    4. Thrombocytopenia: Platelet count < 80 x 109/L
    5. Known abnormal renal function (serum creatinine >2X upper limit for age AND ≥ 1.0 mg/dL)
  • Pregnancy (for post-menarchal females only)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02769845


Contacts
Contact: Russell Ware, MD, PhD 513-636-4266 russell.ware@cchmc.org
Contact: Rebecca Thompson 513-803-7585 Rebecca.Thompson@cchmc.org

Locations
Dominican Republic
Encargada del Servicio de Hematología-Oncología Hospital Infantil Dr. Robert Reid Cabral Recruiting
Santo Domingo, Dominican Republic
Contact: Rosa Nieves, MD    809-533-1111 ext 2004    sacred.rr@gmail.com   
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Hospital Infantil Dr. Robert Reid Cabral
Investigators
Principal Investigator: Russell Ware, MD, PhD Children's Hospital Medical Center, Cincinnati

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT02769845     History of Changes
Other Study ID Numbers: 2015-8767 SACRED
First Posted: May 12, 2016    Key Record Dates
Last Update Posted: August 30, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Anemia
Anemia, Sickle Cell
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn
Hydroxyurea
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors