Sickle Cell AnemiaPhase 3SCATENCT01531387
Sparing Conversion to Abnormal TCD (Transcranial Doppler) Elevation (SCATE)
A Phase 3 study testing Hydroxyurea in people with Sickle Cell Anemia, run by Children's Hospital Medical Center, Cincinnati at 3 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 2 to 10 years
- Conditions the study is for
- Sickle Cell Anemia
- What is being tested?
- Hydroxyurea
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 3 sitesin 3 countries
- Study dates
- May 2012to Jan 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Pediatric subjects with severe forms of sickle cell anemia (HbSS, HbSβ0 thalassemia, HbSD, HbSOArab)
- Age: ≥ 2 and < 11 years of age, at the time of enrollment
- Conditional TCD Velocity (170 - 199cm/sec) by Transcranial Doppler ultrasonography examination within 3 months of enrollment
- Parent or guardian willing and able to provide informed consent
- Ability to comply with study related treatments, evaluations, and follow-up
Who cannot join
- Prior abnormal TCD Velocity
- History of clinical stroke
- Inability to take or tolerate daily oral hydroxyurea, including
- Known allergy to hydroxyurea therapy
- Known positive serology to HIV infection
- Known malignancy
Show all 20Show fewer
- Current lactation
- 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
- 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.
- Current participation in other therapeutic clinical trials
- Serum creatinine more than twice the upper limit for age OR ≥ 1.0 mg/dL
- Any condition or chronic illness, which in the opinion of the clinical investigator makes participation ill-advised
- Pregnancy (for post-menarchal females only)
- Erythrocyte transfusion within the past 2 months
- Previous stem cell transplant or other myelosuppressive therapy
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Brazil1 site
Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti (HEMORIO)
Centro, Rio de Janeiro
Jamaica1 site
Tropical Medicine Research Institute, University of the West Indies (UWI)
Mona, Kingston
About this study
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.
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.
Read the 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.
- Conditions
- Sickle Cell Anemia
- Being tested
- Hydroxyurea
- Keywords
- Phase III, Sickle cell anemia, Conditional transcranial doppler velocities, Reduce risk of conversion to abnormally high transcranial doppler velocities, Pediatric patients
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydroxyureaDrug
Also called Hydroxycarbamide, Hydrea, Droxia
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 group | Role | What they receive |
|---|---|---|
| Standard Therapy: Observation | No intervention | Half of the subjects will be randomized to clinical observation only, which includes monthly visits with clinical evaluations, laboratory tests, and TCD endpoint examinations |
| Hydroxyurea | Experimental | 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. Receives: Drug: Hydroxyurea |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 months
Secondary outcomes (4)
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.
Measured: 30 months
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.
Measured: 30 months
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.
Measured: 30 months
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.
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2012 (estimated)
- Study startMay 2012
- Primary completionJan 2014
- Study completionJan 2014
Why it stopped: inability to reach a satisfactory endpoint with respect to adequate recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell AnemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- 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
- Responsible party
- Sponsor
- Investigators
- Russell E. Ware, MD, PhD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01531387
- Sponsor's protocol ID
- H-29205 SCATE
- Other IDs
- R01HL098239
- Acronym
- SCATE
- Status last verified
- Jan 2016
- First submitted
- 6 Feb 2012
- Last updated
- 8 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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 hydroxyurea in sickle cell anemia: A Phase III international randomized clinical trial. Am J Hematol. 2015 Dec;90(12):1099-105. doi: 10.1002/ajh.24198. Epub 2015 Nov 17.
PubMed 26414435
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01531387
- Acronym / sponsor ID
- SCATE / H-29205 SCATE
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: inability to reach a satisfactory endpoint with respect to adequate recruitment
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- 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
- Study start
- May 2012
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 13 Feb 2012 (estimated)
- Results
- Posted 9 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Therapy: Observation | No intervention | –Half of the subjects will be randomized to clinical observation only, which includes monthly visits with clinical evaluations, laboratory tests, and TCD endpoint examinations |
| Hydroxyurea | Experimental | Drug: HydroxyureaHalf 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. |
Who may qualify
- Ages
- 2 to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Pediatric subjects with severe forms of sickle cell anemia (HbSS, HbSβ0 thalassemia, HbSD, HbSOArab)
- Age: ≥ 2 and < 11 years of age, at the time of enrollment
- Conditional TCD Velocity (170 - 199cm/sec) by Transcranial Doppler ultrasonography examination within 3 months of enrollment
- Parent or guardian willing and able to provide informed consent
- Ability to comply with study related treatments, evaluations, and follow-up
Key exclusion criteria (20 listed)
- Prior abnormal TCD Velocity
- History of clinical stroke
- Inability to take or tolerate daily oral hydroxyurea, including
- Abnormal laboratory values at initial evaluation (temporary exclusions):
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydroxyureaAlso: Hydroxycarbamide, Hydrea, DroxiaHydroxyurea 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. | Drug | Hydroxyurea |
Primary outcome
Conversion to Abnormal Maximum TAMV
Time frame: 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.
4 secondary outcomes
Serial TCD Velocities
Time frame: 30 months
Cumulative Incidence of Neurological Events
Time frame: 30 months
Cumulative Incidence of Non-Neurological Events
Time frame: 30 months
Quality of Life
Time frame: 30 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26414435Hankins 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 hydroxyurea in sickle cell anemia: A Phase III international randomized clinical trial. Am J Hematol. 2015 Dec;90(12):1099-105. doi: 10.1002/ajh.24198. Epub 2015 Nov 17.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Russell E. Ware, MD, PhD principal investigator
Children's Hospital Medical Center, Cincinnati
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hydroxyurea in people with Sickle Cell Anemia, run by Children's Hospital Medical Center, Cincinnati at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Brazil, Jamaica. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Conversion to Abnormal Maximum TAMV (time frame: 30 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01531387, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2016.