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

This study has been terminated.
(inability to reach a satisfactory endpoint with respect to adequate recruitment)
Sponsor:
Collaborators:
St. Jude Children's Research Hospital
Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti (HEMORIO)
Tropical Medicine Research Institute
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:
NCT01531387
First received: February 6, 2012
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Sickle Cell Anemia
Drug: Hydroxyurea
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:
  • Conversion to abnormal maximum TAMV [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
    The primary endpoint of the SCATE trial is the cumulative incidence of conversion to abnormal maximum TAMV (time-averaged mean velocity) measured by transcranial doppler (TCD) ultrasonography. Subjects must have conditional velocities at baseline, defined as 170 - 199 cm/sec, which indicate moderate stroke risk. Abnormal velocities are defined as ≥ 200 cm/sec, which indicate high stroke risk. The number of conversions from conditional velocities to abnormal velocities in each treatment arm will be compared as the primary outcome.


Secondary Outcome Measures:
  • Serial TCD Velocities [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
    This secondary outcome measure will be the highest TAMV obtained in specific arteries. Serial TCD velocities are measured throughout the SCATE trial and will be compared to the baseline value.

  • Cumulative Incidence of Neurological Events [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
    The cumulative incidence of neurological events as a secondary endpoint, which include both stroke and non-stroke neurological events, will be determined over the treatment period for both standard and alternative arms.

  • Cumulative Incidence of Non-Neurological Events [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
    The cumulative incidence of non-neurological sickle cell-related events, including vaso-occlusion and splenic sequestration, will be estimated over the treatment period for both standard and alternative arms.

  • Quality of Life [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Standard Quality of Life measure will be taken during specific time points, as well as one newly-developed Sickle Cell Disease Quality of Life measure.


Enrollment: 38
Study Start Date: May 2012
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Standard Therapy: Observation
Half of the subjects will be randomized to clinical observation only, which includes monthly visits with clinical evaluations, laboratory tests, and TCD endpoint examinations
Experimental: Hydroxyurea
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.
Drug: Hydroxyurea
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.
Other Names:
  • Hydroxycarbamide
  • Hydrea
  • Droxia

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.

  Eligibility

Ages Eligible for Study:   2 Years to 10 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01531387

Locations
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
St. Jude Children's Research Hospital
Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti (HEMORIO)
Tropical Medicine Research Institute
Investigators
Principal Investigator: Russell E. Ware, MD, PhD Children's Hospital Medical Center, Cincinnati
  More Information

No publications provided

Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT01531387     History of Changes
Other Study ID Numbers: H-29205 SCATE, R01HL098239
Study First Received: February 6, 2012
Last Updated: January 27, 2014
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Keywords provided by Children's Hospital Medical Center, Cincinnati:
Phase III
Sickle cell anemia
Conditional transcranial doppler velocities
Reduce risk of conversion to abnormally high transcranial doppler velocities
Pediatric patients

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

ClinicalTrials.gov processed this record on October 21, 2014