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

NCT02769845 | Completed DMC

• 1 other identifier: 2015-8767 SACRED
• Study Type: interventional
• Target: 283
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Sickle Cell Anemia

Outcome Measures

Primary Outcomes (1)

• Transcranial Doppler Ultrasound examinations

  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.

  0-24 months

Secondary Outcomes (1)

• Hydroxyurea toxicities

  0-30 months

Study Arms (2)

Longitudinal Portion

EXPERIMENTAL

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

Treatment Phase

EXPERIMENTAL

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; Procedure: TCD examination

Interventions

Hydroxyurea DRUG

drug to be administered

Treatment Phase

TCD examination PROCEDURE

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.

Longitudinal Portion; Treatment Phase

Eligibility Criteria

• Age: 3 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• For participants with conditional TCD velocities, the following criteria will disqualify them from the treatment phase of SACRED:
• 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):
• Anemia: Hemoglobin concentration \< 6.0 gm/dL
• Reticulocytopenia: Absolute reticulocyte count \< 100 x 10˄9/L with a hemoglobin concentration \< 8.0 gm/dL
• Neutropenia: Absolute neutrophil count (ANC) \< 1.0 x 10˄9/L
• Thrombocytopenia: Platelet count \< 80 x10˄9 /L
• Known abnormal renal function (serum creatinine \>2X upper limit for age AND ≥ 1.0 mg/dL)
• Pregnancy (for post-menarchal females only)

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Hospital Infantil Dr. Robert Reid Cabral: collaborator

Study Sites (1)

Encargada del Servicio de Hematología-Oncología Hospital Infantil Dr. Robert Reid Cabral

Santo Domingo, Dominican Republic

Location

Related Publications (2)

• Nieves RM, Latham T, Marte N, Berges M, Sanchez LM, Urcuyo G, Florencio C, Gonzalez C, Del Villar P, Chen S, Ramirez D, Reyes P, Marinez M, Matos E, Jeste ND, Stuber SE, Schultz WH, Lane AC, Mena R, Ware RE. Stroke prevention in Hispanic children with sickle cell anemia: the SACRED trial. Blood Adv. 2025 Apr 22;9(8):1791-1800. doi: 10.1182/bloodadvances.2024014327.

  PMID: 39820633 DERIVED

• Jeste ND, Sanchez LM, Urcuyo GS, Berges ME, Luden JP, Stuber SE, Latham TS, Mena R, Nieves RM, Ware RE. Stroke Avoidance for Children in REpublica Dominicana (SACRED): Protocol for a Prospective Study of Stroke Risk and Hydroxyurea Treatment in Sickle Cell Anemia. JMIR Res Protoc. 2017 Jun 2;6(6):e107. doi: 10.2196/resprot.7491.

  PMID: 28576754 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Study Officials

• Russell Ware, MD, PhD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2016
• First Posted: May 12, 2016
• Study Start: March 16, 2016
• Primary Completion: July 1, 2019
• Study Completion: October 1, 2022
• Last Updated: August 22, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

DO (1)