NCT01531387

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.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
38

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started May 2012

Geographic Reach
3 countries

3 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 6, 2012

Completed
7 days until next milestone

First Posted

Study publicly available on registry

February 13, 2012

Completed
3 months until next milestone

Study Start

First participant enrolled

May 1, 2012

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2014

Completed
1.9 years until next milestone

Results Posted

Study results publicly available

December 9, 2015

Completed
Last Updated

February 8, 2016

Status Verified

January 1, 2016

Enrollment Period

1.7 years

First QC Date

February 6, 2012

Results QC Date

June 19, 2015

Last Update Submit

January 13, 2016

Conditions

Sickle Cell Anemia

Keywords

Phase IIISickle cell anemiaConditional transcranial doppler velocitiesReduce risk of conversion to abnormally high transcranial doppler velocitiesPediatric patients

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (4)

  • 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

Study Arms (2)

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.

Drug: Hydroxyurea

Interventions

HydroxyureaDRUG

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.

Also known as: Hydroxycarbamide, Hydrea, Droxia
Hydroxyurea

Eligibility Criteria

Age2 Years - 10 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • Current lactation
  • 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
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti (HEMORIO)

Centro, Rio de Janeiro, Brazil

Location

Tropical Medicine Research Institute, University of the West Indies (UWI)

Mona, Kingston, Jamaica

Location

Related 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 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.

    PMID: 26414435RESULT

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, CongenitalAnemia, HemolyticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesHemoglobinopathiesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

UreaAmidesOrganic Chemicals

Results Point of Contact

Title
James M. Boyett, PhD
Organization
St. Jude Children's Research Hospital
james.boyett@stjude.org
901-595-4986

Study Officials

  • Russell E. Ware, MD, PhD

    Children's Hospital Medical Center, Cincinnati

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 6, 2012

First Posted

February 13, 2012

Study Start

May 1, 2012

Primary Completion

January 1, 2014

Study Completion

January 1, 2014

Last Updated

February 8, 2016

Results First Posted

December 9, 2015

Record last verified: 2016-01

Locations

US(1)BR(1)JA(1)