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

• ClinicalTrials.gov Identifier: NCT02769845
• Recruitment Status: Active, not recruiting
• First Posted: May 12, 2016
• Last Update Posted: January 19, 2023
• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborator: Hospital Infantil Dr. Robert Reid Cabral
• Information provided by (Responsible Party): Children's Hospital Medical Center, Cincinnati

Tracking Information

• First Submitted Date: May 10, 2016
• First Posted Date: May 12, 2016
• Last Update Posted Date: January 19, 2023
• Actual Study Start Date: March 16, 2016
• Actual Primary Completion Date: July 1, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 10, 2016)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 10, 2016)

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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: SACRED A Prospective Research Study to Reduce Stroke in Children With Sickle Cell Anemia
• Official Title: Stroke Avoidance for Children in REpublica Dominicana (SACRED): A Prospective Research Study to Reduce Stroke in Children With Sickle Cell Anemia
• Brief Summary: Prospective screening and treatment study for children with Sickle Cell Anemia and increased stroke risk living in the Dominican Republic.

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
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Supportive Care
• Condition: Sickle Cell Anemia

Intervention

• 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.

Study Arms

• 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.
  Intervention: Procedure: TCD examination
• 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.
  Interventions:

  • Drug: Hydroxyurea
  • Procedure: TCD examination

• Publications *: 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 27, 2018): 283
• Original Estimated Enrollment (submitted: May 10, 2016): 500
• Estimated Study Completion Date: July 31, 2025
• Actual Primary Completion Date: July 1, 2019 (Final data collection date for primary outcome measure)

Eligibility 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 10˄9/L with a hemoglobin concentration < 8.0 gm/dL
  3. Neutropenia: Absolute neutrophil count (ANC) < 1.0 x 10˄9/L
  4. Thrombocytopenia: Platelet count < 80 x10˄9 /L
  5. Known abnormal renal function (serum creatinine >2X upper limit for age AND ≥ 1.0 mg/dL)
• Pregnancy (for post-menarchal females only)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Years to 15 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Dominican Republic

Administrative Information

• NCT Number: NCT02769845
• Other Study ID Numbers: 2015-8767 SACRED
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Children's Hospital Medical Center, Cincinnati
• Original Responsible Party: Same as current
• Current Study Sponsor: Children's Hospital Medical Center, Cincinnati
• Original Study Sponsor: Same as current
• Collaborators: Hospital Infantil Dr. Robert Reid Cabral

Investigators

• Principal Investigator: Russell Ware, MD, PhD; Children's Hospital Medical Center, Cincinnati

• PRS Account: Children's Hospital Medical Center, Cincinnati
• Verification Date: January 2023