Sickle Cell Disease - Stroke Prevention in Nigeria Trial

NCT01801423 | Completed DMC

• 2 other identifiers: 1R01NS094041-011R21NS080639-01
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

Given large absolute numbers of individuals with sickle cell disease in Nigeria, hydroxyurea therapy for all individuals with sickle cell disease may not be initially feasible; however, a targeted strategy of hydroxyurea use for primary prevention of strokes is an alternative to the standard therapy (observation) for high-risk individuals. The investigators propose a feasibility study, Sickle Cell Disease - Stroke Prevention in Nigeria (SPIN) Trial, to determine whether hydroxyurea can be used for primary prevention of strokes in Nigerian children with sickle cell anemia.

Conditions

Sickle Cell Anemia; Sickle Cell Disease; Stroke

Keywords

transcranial Doppler; stroke; sickle cell anemia; Nigeria; hydroxyurea; low income country

Outcome Measures

Primary Outcomes (1)

• Hydroxyurea Therapy Acceptance and Adherence

  The primary outcome measure will be adherence to daily administration of hydroxyurea. If adherence rate is less than 55%, alternative strategies must be considered for the definitive Phase III Trial.

  5 years

Secondary Outcomes (1)

• Hydroxyurea Safety protocol for Children with Sickle Cell Anemia

  12 Months

Other Outcomes (1)

• Feasibility of a Definitive Phase III Trial for Hydroxyurea Therapy to Prevent Strokes in Sickle Cell Disease

  24 Months

Study Arms (1)

Hydroxyurea

EXPERIMENTAL

Study investigators propose to enroll 60 children with SCA and an elevated TCD measurement between 5 and 12 years of age in this one arm feasibility study of hydroxyurea therapy, with follow-up of at least 12 months per subject. The study intervention will include HU to begin at \~ 20 mg/kg/day(range 17.5 - 26 mg/kg/day). No dose escalation will occur. Given the success of the first year of enrollment and the favorable response of TCD measurement after 3 months on HU therapy, the study investigators have participants as an internal pilot. The definitive phase III trial will now compare low dose HU therapy to the result of no treatment arm from the STOP Trial.

Drug: Hydroxyurea

Interventions

Hydroxyurea DRUG

Hydroxyurea will be prescribed as an investigational therapy by the treating physician. Recommended guidelines for titration of hydroxyurea to maximal tolerated dose are below. The study intervention will include hydroxyurea to begin at \~20 mg/kg/day (range 17.5 - 26 mg/kg/day). No dose escalation will occur as this dose was shown to have some efficacy in infants with SCA and was associated with rare myelosuppression.(1)

Also known as: Droxia, Hydrea, Mylocel

Hydroxyurea

Eligibility Criteria

• Age: 5 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patients with hemoglobin SS or S beta zero thalassemia confirmed by hemoglobin electrophoresis;
• Informed consent from a parent or legal guardian and assent of participant ages 5 through 12;
• Successful completion of screening procedures: cerebral blood flow velocity ≥ 200 cm/sec in the terminal portion of the middle cerebral artery;
• Patient must be 5 through 12 years of age (i.e., must have attained their 5th but not their 13th birthday when the consent is signed).

You may not qualify if:

• Prior overt stroke (a focal neurological deficit of acute onset) by history, focal neurological deficit on standardized neurological examination, or concern for moderate or severe neurological deficit (which could be due to stroke) based on a positive "10 questions" screening (an established tool in resource poor countries).(2,3) A "positive" screening is defined as answering yes to any one of the 10 questions. The negative predictive value (child does not have moderate or several neurological impairment) of the "10 questions" is greater than 94% in children (2);
• Patients for whom hydroxyurea therapy is under consideration prior to study consent/education;
• Patients who have previously been treated with hydroxyurea and are being considered to restart hydroxyurea therapy;
• Other significant organ system dysfunction;
• Any other condition or chronic illness, which in the opinion of the site's Principal Investigator (PI) makes participation ill-advised or unsafe.
• Participants of child bearing age who are pregnant or may become pregnant should not take hydroxyurea. If a participant becomes pregnant during the study, their hydroxyurea treatment will be stopped immediately. The onsite will notify the clinical coordinating center and the principal investigators of the case. The site principal investigator and study principal investigators will determine what therapy the participant should receive during pregnancy that is of standard care.
• Successful completion of screening procedures inclusive of cerebral blood flow velocity greater than or equal to 200 cm/sec measured twice or at least one measurement greater than or equal to 220 cm/sec in the terminal portion of the middle cerebral artery or two TCD measurements above 190 cm/sec within a three month interval;
• Informed consent from a parent or legal guardian for study therapy and assent of the participant completed;
• Participant is able to swallow a capsule as observed by study personnel;
• Acceptance of hydroxyurea therapy for one year. After one year of therapy, the participant will have the option to continue therapy with follow up visits to monitor adherence to therapy.
• \- Unable to commit to follow up visits for the course of the study.
• Successful completion of screening procedures inclusive of cerebral blood flow velocity less than or equal to 199 cm/sec in the terminal portion of the middle cerebral artery;
• Informed consent from a parent or legal guardian and assent from the participant;
• Acceptance to be followed for one year in the study. Hydroxyurea may be given for other reasons as part of the participant's ongoing care, but it will not be given as part of the study.
• \- Unable to commit to follow up visits for the course of the study.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Aminu Kano Teaching Hospital: collaborator

Study Sites (1)

Aminu Kano Teaching Hospital

Kano, P.MB. 3452, Nigeria

Location

Related Publications (3)

• Wang WC, Ware RE, Miller ST, Iyer RV, Casella JF, Minniti CP, Rana S, Thornburg CD, Rogers ZR, Kalpatthi RV, Barredo JC, Brown RC, Sarnaik SA, Howard TH, Wynn LW, Kutlar A, Armstrong FD, Files BA, Goldsmith JC, Waclawiw MA, Huang X, Thompson BW; BABY HUG investigators. Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet. 2011 May 14;377(9778):1663-72. doi: 10.1016/S0140-6736(11)60355-3.

  PMID: 21571150 BACKGROUND

• Mung'ala-Odera V, Meehan R, Njuguna P, Mturi N, Alcock K, Carter JA, Newton CR. Validity and reliability of the 'Ten Questions' questionnaire for detecting moderate to severe neurological impairment in children aged 6-9 years in rural Kenya. Neuroepidemiology. 2004 Jan-Apr;23(1-2):67-72. doi: 10.1159/000073977.

  PMID: 14739570 BACKGROUND

• Mung'ala-Odera V, Newton CR. Identifying children with neurological impairment and disability in resource-poor countries. Child Care Health Dev. 2007 May;33(3):249-56. doi: 10.1111/j.1365-2214.2006.00714.x.

  PMID: 17439437 BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell; Stroke

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; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Study Officials

• Michael R. DeBaun, MD, MPH

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

• Muktar Aliyu, MBBS, MPH, DrPH

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

• Lori Jordan, MD, PhD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Chair for Clinical Research, JC Peterson Endowed Chair, Professor of Pediatrics and Medicine, Director, Vanderbilt-Meharry-Matthew Walker Center of Excellence in Sickle Cell Disease

Study Record Dates

• First Submitted: February 26, 2013
• First Posted: February 28, 2013
• Study Start: April 24, 2013
• Primary Completion: January 31, 2019
• Study Completion: January 31, 2019
• Last Updated: August 3, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

NG (1)