NCT02675790

Brief Summary

The overall goal of the proposed study is to determine the effectiveness of hydroxyurea therapy for secondary stroke prevention and prevention of other neurological events in children with SCA with an acute overt stroke.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
120

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Jan 2017

Typical duration for phase_3

Geographic Reach
1 country

2 active sites

Status
completed

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

January 8, 2016

Completed
28 days until next milestone

First Posted

Study publicly available on registry

February 5, 2016

Completed
11 months until next milestone

Study Start

First participant enrolled

January 1, 2017

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2020

Completed
Last Updated

January 19, 2022

Status Verified

January 1, 2022

Enrollment Period

3.2 years

First QC Date

January 8, 2016

Last Update Submit

January 16, 2022

Conditions

Sickle Cell DiseaseSickle Cell AnemiaStroke

Keywords

hydroxyureasub-Saharan Africasecondary stroke prevention

Outcome Measures

Primary Outcomes (1)

  • Recurrence of clinically overt stroke, transient ischemic attack or death

    To assess the effectiveness of moderate dose HU therapy at 20 mg/kg/day for secondary stroke prevention when compared to low dose HU therapy at 10 mg/kg/day in children with SCA. Within 30 days after the onset of a first stroke, children 1 to 16 years of age with SCA will be randomized to receive moderate dose HU therapy at 20 mg/kg/day (study group) or low dose HU therapy at 10 mg/kg/day (control group) with monthly follow-up for at least 36 months per participant. Parents will be educated on how to recognize signs and symptoms of a stroke. The rate of stroke recurrence will be measured using standardized neurological examinations (Pediatric NIH Stroke Scale).

    36 months

Secondary Outcomes (1)

  • Incidence of all cause hospitalizations

    36 months

Other Outcomes (1)

  • Prevalence of stroke and incidence of recurrent strokes

    42 months

Study Arms (2)

Hydroxyurea (Moderate Dose)

ACTIVE COMPARATOR

The study intervention will include moderate dose hydroxyurea therapy at 20 mg/kg/day (range 17.5 - 26 mg/kg/day) for 36 months.

Drug: Moderate Dose Hydroxyurea

Hydroxyurea (Low Dose)

ACTIVE COMPARATOR

The study intervention will include random allocation to low dose hydroxyurea therapy at 10 mg/kg/day (range 7 - 15 mg/kg/day) for 36 months.

Drug: Low Dose Hydroxyurea

Interventions

Moderate Dose HydroxyureaDRUG

Hydroxyurea therapy at 20 mg/kg/day for primary stroke prevention.

Also known as: Hydrea
Hydroxyurea (Moderate Dose)
Low Dose HydroxyureaDRUG

Hydroxyurea therapy at 10 mg/kg/day (range 7 - 15 mg/kg/day) for primary stroke prevention.

Also known as: Hydrea
Hydroxyurea (Low Dose)

Eligibility Criteria

Age1 Year - 16 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Children ages 1 to 16 years of age with sickle cell anemia confirmed by hemoglobin electrophoresis evaluation or high performance liquid chromatography (HPLC);
  • Informed consent from a parent or legal guardian and assent of participants;
  • Children with presence of new stroke up to and including 30 days prior to signing the informed consent;
  • Acceptance of HU therapy for at least three years.

You may not qualify if:

  • Children with history of stroke with event occurring more than 30 days prior to signing the informed consent;
  • Confirmed pregnancy or considering family planning - due to possible hydroxyurea-induced congenital anomalies or abnormal fetal growth. Adolescents who have started their menses must have a pregnancy test done every month prior to getting a prescription for HU;
  • Children who are already on blood transfusion or HU therapy;
  • Other significant organ system dysfunction based on the site investigators discretion;
  • Any other condition, such as malnutrition, or chronic illness, which in the opinion of the site's Principal Investigator makes study therapy not advisable or unsafe;
  • Active infections: bacterial, viral or fungal (tuberculosis, malaria, active hepatitis, osteomyelitis);
  • Active chronic leg ulcers.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Aminu Kano Teaching Hospital

Kano, Nigeria

Location

Murtala Muhammad Specialist Hospital

Kano, Nigeria

Location

Related Publications (3)

  • Ohene-Frempong K, Weiner SJ, Sleeper LA, Miller ST, Embury S, Moohr JW, Wethers DL, Pegelow CH, Gill FM. Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood. 1998 Jan 1;91(1):288-94.

    PMID: 9414296BACKGROUND

  • Kassim AA, Galadanci NA, Pruthi S, DeBaun MR. How I treat and manage strokes in sickle cell disease. Blood. 2015 May 28;125(22):3401-10. doi: 10.1182/blood-2014-09-551564. Epub 2015 Mar 30.

    PMID: 25824688BACKGROUND

  • Abdullahi SU, DeBaun MR, Jordan LC, Rodeghier M, Galadanci NA. Stroke Recurrence in Nigerian Children With Sickle Cell Disease: Evidence for a Secondary Stroke Prevention Trial. Pediatr Neurol. 2019 Jun;95:73-78. doi: 10.1016/j.pediatrneurol.2019.01.008. Epub 2019 Jan 17.

    PMID: 30952488DERIVED

MeSH Terms

Conditions

Anemia, Sickle CellStroke

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, CongenitalAnemia, HemolyticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesHemoglobinopathiesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

UreaAmidesOrganic Chemicals

Study Officials

  • Michael R. DeBaun, MD, MPH

    Vanderbilt University Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

January 8, 2016

First Posted

February 5, 2016

Study Start

January 1, 2017

Primary Completion

March 31, 2020

Study Completion

March 31, 2020

Last Updated

January 19, 2022

Record last verified: 2022-01

Data Sharing

IPD Sharing
Will not share

Locations

NG(2)