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.

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01531387

Acronym

SCATE

Enrollment

Registered

2012-02-13

Start date

2012-05-31

Completion date

2014-01-31

Last updated

2016-02-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Sickle Cell Anemia

Keywords

Phase III, Sickle cell anemia, Conditional transcranial doppler velocities, Reduce risk of conversion to abnormally high transcranial doppler velocities, Pediatric patients

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.

Interventions

DRUGHydroxyurea

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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

2 Years to 10 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Conversion to Abnormal Maximum TAMV	30 months	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

Measure	Time frame	Description
Serial TCD Velocities	30 months	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	30 months	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	30 months	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	30 months	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.

Countries

Brazil, Jamaica, United States

Participant flow

Pre-assignment details

22 participants were randomized (e.g., a total of 38 participants enrolled, but only 22 participants were randomized to treatment)

Participants by arm

Arm	Count
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	11
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. 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.	11
Total	22

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Early termination of study	11	11

Baseline characteristics

Characteristic	Standard Therapy: Observation	Hydroxyurea	Total
Age, Categorical <=18 years	11 Participants	11 Participants	22 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	0 Participants	0 Participants	0 Participants
Age, Continuous	6.3 Years STANDARD_DEVIATION 1.5	6 Years STANDARD_DEVIATION 2.4	6.15 Years STANDARD_DEVIATION 1.95
Region of Enrollment Brazil	2 participants	3 participants	5 participants
Region of Enrollment Jamaica	7 participants	6 participants	13 participants
Region of Enrollment United States	2 participants	2 participants	4 participants
Sex: Female, Male Female	7 Participants	7 Participants	14 Participants
Sex: Female, Male Male	4 Participants	4 Participants	8 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	7 / 11	7 / 11
serious Total, serious adverse events	6 / 11	11 / 11

Population: No participants reached 30 months of treatment prior to study termination; therefore, the secondary outcome measures were not analyzed.

Source: ClinicalTrials.gov · Data processed: Mar 12, 2026