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

Sickle Cell Anemia Clinical Trial

— SCATE  

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01531387
• Other study ID #: H-29205 SCATE
• Secondary ID: R01HL098239
• Status: Terminated
• Phase: Phase 3
• First received: February 6, 2012
• Last updated: January 13, 2016
• Start date: May 2012
• Est. completion date: January 2014

Study information

• Verified date: January 2016
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 38
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 10 Years

Eligibility

Inclusion Criteria:

1. Pediatric subjects with severe forms of sickle cell anemia (HbSS, HbSß0 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Anemia

Intervention

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.

Locations

Country	Name	City	State
Brazil	Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti (HEMORIO)	Centro	Rio de Janeiro
Jamaica	Tropical Medicine Research Institute, University of the West Indies (UWI)	Mona	Kingston
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (5)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	HEMORIO – State institute of Hematology Arthur de Siqueira Cavalcanti (English), National Heart, Lung, and Blood Institute (NHLBI), St. Jude Children's Research Hospital, Tropical Medicine Research Institute

Countries where clinical trial is conducted

United States,  Brazil,  Jamaica, 

References & Publications (1)

Hankins JS, McCarville MB, Rankine-Mullings A, Reid ME, Lobo CL, Moura PG, Ali S, Soares DP, Aldred K, Jay DW, Aygun B, Bennett J, Kang G, Goldsmith JC, Smeltzer MP, Boyett JM, Ware RE. Prevention of conversion to abnormal transcranial Doppler with hydrox — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Conversion to Abnormal Maximum TAMV	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.	30 months	Yes
Secondary	Serial TCD Velocities	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.	30 months	Yes
Secondary	Cumulative Incidence of Neurological Events	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.	30 months	Yes
Secondary	Cumulative Incidence of Non-Neurological Events	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.	30 months	Yes
Secondary	Quality of Life	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.	30 months	No