Sparing Conversion to Abnormal TCD (Transcranial Doppler) Elevation (SCATE)

Sparing Conversion to Abnormal TCD Elevation (SCATE) - a Phase III Clinical Trial to Compare Standard Care (Observation) With Alternative Therapy (Hydroxyurea) for Reducing the Risk of Converting to an Abnormal TCD Velocity in Children With Sickle Cell Anemia and Conditional Pre-treatment TCD Velocities.

Sponsors

Lead Sponsor: Children's Hospital Medical Center, Cincinnati

Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
St. Jude Children's Research Hospital
Tropical Medicine Research Institute
Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti

Source Children's Hospital Medical Center, Cincinnati
Brief Summary

The primary goal of the Phase III SCATE trial is to compare 30 months of alternative therapy (hydroxyurea) to standard care (observation) in children with sickle cell anemia and conditional (170 - 199cm/sec) Transcranial Doppler (TCD) velocities. For the alternative regimen (hydroxyurea) to be declared superior to the standard treatment regimen (observation), the hydroxyurea-treated group must have a three-fold reduction in the incidence of conversion to abnormal TCD velocities (≥ 200 cm/sec), compared to the standard treatment arm.

Detailed Description

Results from previous studies confirm an increased risk of stroke among children with conditional TCD velocities. In addition, studies suggest that patients who were on observation alone, converted from conditional TCD (moderate risk category) to an abnormal TCD (with a much higher risk for primary stroke) within 30 months of initial identification of the conditional TCD velocity; this conversion led to initiation of chronic and indefinite transfusions in all cases. Preliminary data suggests that the risk of conversion to abnormal TCD velocities will be lower for subjects with conditional TCD velocities on hydroxyurea by at least three-fold. This important difference in conversion risk rate suggests that an alternative treatment could have a substantial and beneficial impact on patients with elevated TCD velocities.

An alternative treatment could protect the brain of patients with SCA and conditional TCD velocities who are at increased risk for stroke. The avoidance of chronic blood transfusions would be a great benefit for all children with sickle cell disease, especially those in developing countries where the blood supply may be less safe (in comparison with that in the US) or unavailable, and very costly.

Overall Status Terminated
Start Date May 2012
Completion Date January 2014
Primary Completion Date January 2014
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Conversion to Abnormal Maximum TAMV 30 months
Secondary Outcome
Measure Time Frame
Serial TCD Velocities 30 months
Cumulative Incidence of Neurological Events 30 months
Cumulative Incidence of Non-Neurological Events 30 months
Quality of Life 30 months
Enrollment 38
Condition
Intervention

Intervention Type: Drug

Intervention Name: Hydroxyurea

Description: Hydroxyurea will be administered once daily, in either capsule form (300mg, 400mg, or 500mg) or as a liquid formulation (100mg/ml). Dosing will commence at 20 mg/kg/day. Dose escalation will occur in 5 mg/kg/day increments, adjusting every 8 weeks unless hematological toxicity occurs.

Arm Group Label: Hydroxyurea

Eligibility

Criteria:

Inclusion Criteria:

1. Pediatric subjects with severe forms of sickle cell anemia (HbSS, HbSβ0 thalassemia, HbSD, HbSOArab)

2. Age: ≥ 2 and < 11 years of age, at the time of enrollment

3. Conditional TCD Velocity (170 - 199cm/sec) by Transcranial Doppler ultrasonography examination within 3 months of enrollment

4. Parent or guardian willing and able to provide informed consent

5. Ability to comply with study related treatments, evaluations, and follow-up

Exclusion Criteria:

1. Prior abnormal TCD Velocity

2. History of clinical stroke

3. Inability to take or tolerate daily oral hydroxyurea, including

- Known allergy to hydroxyurea therapy

- Known positive serology to HIV infection

- Known malignancy

- Current lactation

4. Abnormal laboratory values at initial evaluation (temporary exclusions):

- Hemoglobin concentration < 6.0 gm/dL

- Absolute reticulocyte count < 100 x 10^9/L with a hemoglobin concentration < 8.0 gm/dL

- WBC count < 3.0 x 10^9/L

- Absolute neutrophil count (ANC) < 1.0 x 10^9/L

- Platelet count < 100 x 10^9/L

5. Current use of therapeutic agents for sickle cell disease (e.g., hydroxyurea, arginine, decitabine, magnesium, chronic transfusions). Subjects must be off therapeutic agents for sickle cell disease for at least 3 months prior to enrollment.

6. Current participation in other therapeutic clinical trials

7. Serum creatinine more than twice the upper limit for age OR ≥ 1.0 mg/dL

8. Any condition or chronic illness, which in the opinion of the clinical investigator makes participation ill-advised

9. Pregnancy (for post-menarchal females only)

10. Erythrocyte transfusion within the past 2 months

11. Previous stem cell transplant or other myelosuppressive therapy

Gender: All

Minimum Age: 2 Years

Maximum Age: 10 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Russell E. Ware, MD, PhD Principal Investigator Children's Hospital Medical Center, Cincinnati
Location
Facility:
St. Jude Children's Research Hospital | Memphis, Tennessee, 38105, United States
Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti (HEMORIO) | Centro, Rio de Janeiro, Brazil
Tropical Medicine Research Institute, University of the West Indies (UWI) | Mona, Kingston, Jamaica
Location Countries

Brazil

Jamaica

United States

Verification Date

January 2016

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Standard Therapy: Observation

Type: No Intervention

Description: Half of the subjects will be randomized to clinical observation only, which includes monthly visits with clinical evaluations, laboratory tests, and TCD endpoint examinations

Label: Hydroxyurea

Type: Experimental

Description: Half of the subjects will be randomized to hydroxyurea, taken as capsules (300 mg, 400 mg, or 500 mg), or as a liquid formulation (100 mg/mL). Hydroxyurea will be administered once daily by mouth. Subjects will be monitored monthly with clinical evaluations, laboratory tests, and TCD endpoint examinations.

Acronym SCATE
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Prevention

Masking: None (Open Label)

Source: ClinicalTrials.gov