EXTEND EXpanding Treatment for Existing Neurological Disease

NCT02556099 | Completed Phase 2 DMC

• 1 other identifier: 2014-2875 EXTEND
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

The primary goal of the Phase II EXTEND trial is to investigate the effects of open-label hydroxyurea treatment, escalated to maximum tolerated dose, for children with Sickle Cell Anemia and either conditional (170 - 199 cm/sec) or abnormal (≥200 cm/sec) Transcranial Doppler velocities. The primary endpoint will be measured after 18 months of hydroxyurea but treatment will continue until a common study termination date.

Conditions

Sickle Cell Anemia

Outcome Measures

Primary Outcomes (1)

• Maximum Time-Averaged Mean velocity (TAMV) on TCD exam

  The primary endpoint of the EXTEND trial is the maximum Time-Averaged Mean velocity (TAMV) on TCD exam performed after 18 months of hydroxyurea treatment, compared to pre-treatment velocity.

  18 months

Secondary Outcomes (5)

• Serial TCD velocities

  Screening, Baseline, month 6, month 12, month 18

• The cumulative incidence of neurological events

  Screening/Baseline and approximately 3 years after the first enrollment

• Cumulative Incidence of Non-Neurological Events

  Screening/Baseline and approximately 3 years after the first enrollment

• Quality of Life Assessment

  Baseline, 18 months, and approximately 3 years after the first enrollment

• Neuropsychological Assessment

  Baseline, after 18 months

Study Arms (1)

Hydroxyurea Treatment

EXPERIMENTAL

Hydroxyurea will be administered once daily by mouth. Participants will be monitored monthly to maximum tolerated dose and quarterly thereafter with periodic clinical evaluations, laboratory tests, and transcranial doppler examinations every 6 months.

Drug: Hydroxyurea

Interventions

Hydroxyurea DRUG

drug to be administered

Hydroxyurea Treatment

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Pediatric participants with a severe form of sickle cell anemia (HbSS, HbSβ0 thalassemia, HbSD, HbSOArab)
• Age: ≥ 2 and ≤ 17 years of age, at the time of enrollment
• Time-averaged maximum velocity (TAMV) TCD Velocity in the conditional (170 - 199 cm/sec) or abnormal (≥200 cm/sec) range by Transcranial Doppler ultrasonography examination within 6 months of enrollment, abnormal or conditional TCD velocity and currently on commercial hydroxyurea for primary stroke prevention, or previously enrolled in SCATE, a previous stroke with abnormal or conditional TCD prior to stroke event.
• Parent or guardian willing and able to provide informed consent and child gives assent
• Ability to comply with study related treatments, evaluations, and follow- up visits

You may not qualify if:

• Inability to take or tolerate daily oral hydroxyurea, including
• Known allergy to hydroxyurea therapy
• Known positive serology to HIV infection
• Known malignancy
• Current lactation
• Abnormal historical laboratory values (most recent pre-enrollment values unless previously enrolled in SCATE):
• Hemoglobin concentration \< 6.0 gm/dL
• Absolute reticulocyte count \< 100 x 109/L with a hemoglobin concentration \< 8.0 gm/dL
• White Blood Cell (WBC) count \< 3.0 x 109/L
• Absolute neutrophil count (ANC) \< 1.0 x 109/L
• Platelet count \< 100 x 109/L
• Use of therapeutic agents for sickle cell disease (e.g., hydroxyurea, arginine, decitabine, magnesium, chronic transfusions) within 3 months of enrollment unless they have an abnormal TCD velocity and receive commercial hydroxyurea for primary stroke prevention or were previously enrolled in the SCATE study or for secondary stroke prevention in a child with a previous stroke.
• Current participation in other therapeutic clinical trials, except SCATE
• Known serum creatinine more than twice the upper limit for age AND
• mg/dL

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Caribbean Institute for Health Research (CAIHR): collaborator

Study Sites (1)

Sickle Cell Unit

Kingston, Jamaica

Location

Related Publications (2)

• Power-Hays A, McElhinney KE, Williams TN, Mochamah G, Olupot-Olupot P, Paasi G, Reid ME, Rankine-Mullings AE, Opoka RO, John CC, McGann PT, Quinn CT, Punt NC, Smart LR, Stuber SE, Latham TS, Vinks AA, Ware RE. Hydroxyurea pharmacokinetics in children with sickle cell anemia across different global populations. Blood Adv. 2026 Jan 27;10(2):418-427. doi: 10.1182/bloodadvances.2025017254.

  PMID: 41026975 DERIVED

• Rankine-Mullings AE, Little CR, Reid ME, Soares DP, Taylor-Bryan C, Knight-Madden JM, Stuber SE, Badaloo AV, Aldred K, Wisdom-Phipps ME, Latham T, Ware RE. EXpanding Treatment for Existing Neurological Disease (EXTEND): An Open-Label Phase II Clinical Trial of Hydroxyurea Treatment in Sickle Cell Anemia. JMIR Res Protoc. 2016 Sep 12;5(3):e185. doi: 10.2196/resprot.5872.

  PMID: 27619954 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Study Officials

• Russell Ware, MD, PhD

  Cincinnati Children's

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2015
• First Posted: September 22, 2015
• Study Start: August 1, 2014
• Primary Completion: January 16, 2023
• Study Completion: January 16, 2023
• Last Updated: August 22, 2025

Record last verified: 2025-07

Locations

JA (1)