NCT01976416

Brief Summary

Multiple studies have shown that hydroxyurea has clinical efficacy in preventing acute painful episodes and reducing the need for blood transfusions in children with sickle cell anemia (SCA), but no study has been conducted in malaria endemic regions of sub-Saharan Africa, the areas with the most children with SCA. The primary goal of this study is to investigate the safety and efficacy of hydroxyurea for children with SCA in a malaria endemic region within sub-Saharan Africa.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
208

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Sep 2014

Typical duration for phase_3

Geographic Reach
1 country

1 active site

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

October 22, 2013

Completed
14 days until next milestone

First Posted

Study publicly available on registry

November 5, 2013

Completed
10 months until next milestone

Study Start

First participant enrolled

September 1, 2014

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2016

Completed
1.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2017

Completed
11 months until next milestone

Results Posted

Study results publicly available

October 1, 2018

Completed
Last Updated

December 4, 2018

Status Verified

November 1, 2018

Enrollment Period

2.1 years

First QC Date

October 22, 2013

Results QC Date

February 2, 2018

Last Update Submit

November 7, 2018

Conditions

Sickle Cell AnemiaSickle Cell DiseaseMalaria

Keywords

Hydroxyurea

Outcome Measures

Primary Outcomes (1)

  • Number of Malaria Episodes

    Malaria is defined as the presence of P. falciparum or P. malariae on the peripheral smear of any child brought in for medical evaluation of fever. P. vivax, P. ovale and P. knowlesi are not known to be present in this region, but if a child is seen with suspected infection with any of these malaria parasites, this will also be recorded as a case of malaria. Incidence will be reported in the number of cases per 100 patient years.

    12 months

Study Arms (2)

Hydroxyurea

EXPERIMENTAL

Fixed dose 20 ± 2.5 mg/kg/day, administered once a day in tablet form (100mg or scored 1000mg) for twelve months

Drug: Hydroxyurea

Placebo

PLACEBO COMPARATOR

Fixed dose 20 ± 2.5 mg/kg/day, administered once a day in tablet form (100mg or scored 1000mg) for twelve months

Drug: Placebo

Interventions

HydroxyureaDRUG
Also known as: Siklos, Hydroxycarbamide
Hydroxyurea
PlaceboDRUG
Placebo

Eligibility Criteria

Age12 Months - 47 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Pediatric subjects with documented sickle cell anemia (HbSS supported by hemoglobin electrophoresis or by peripheral blood smear showing sickled red blood cells)
  • Age range of 1.00-3.99 years, inclusive, at the time of enrollment
  • Weight at least 5.0 kg at the time of enrollment
  • Willingness to comply with all study-related treatments, evaluations, and follow up

You may not qualify if:

  • Known chronic medical condition (e.g., HIV, malignancy, active clinical tuberculosis)
  • Severe malnutrition determined by impaired growth parameters as defined by WHO (weight for length/height or weight-for-length/height \> 3 z-scores below the median WHO growth standards)
  • Pre-existing severe hematological toxicity:
  • Hb \<4.0 g/dL
  • Hb \<6.0 g/dL AND ARC \<100 x 10E9/L
  • Hb \<7.0 g/dL AND ARC \<80 x 10E9/L
  • Platelets \<80 x 10E9/L
  • ANC \<1.0 x 10E9/L
  • Alanine transaminase (ALT) or creatinine \>2 times the upper limit of normal for age
  • Blood transfusion within 30 days prior to enrollment

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Mulago Hospital Sickle Cell Clinic

Kampala, Uganda

Location

Related Publications (5)

  • Opoka RO, Ndugwa CM, Latham TS, Lane A, Hume HA, Kasirye P, Hodges JS, Ware RE, John CC. Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia. Blood. 2017 Dec 14;130(24):2585-2593. doi: 10.1182/blood-2017-06-788935. Epub 2017 Oct 19.

    PMID: 29051184RESULT

  • 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: 41026975DERIVED

  • Siegert TF, Opoka RO, Nakafeero M, Carman A, Mellencamp KA, Latham T, Hume H, Lane A, Ware RE, Ssenkusu JM, John CC, Conroy AL. Angiopoietin-2 is associated with sickle cell complications, including stroke risk, and decreases with hydroxyurea therapy. Blood Vessel Thromb Hemost. 2024 Feb 8;1(1):100001. doi: 10.1016/j.bvth.2024.100001. eCollection 2024 Mar.

    PMID: 40765704DERIVED

  • Carman AS, Sautter C, Anyanwu JN, Ssemata AS, Opoka RO, Ware RE, Rujumba J, John CC. Perceived benefits and risks of participation in a clinical trial for Ugandan children with sickle cell anemia. Pediatr Blood Cancer. 2020 Feb;67(2):e27830. doi: 10.1002/pbc.27830. Epub 2019 May 28.

    PMID: 31135090DERIVED

  • Anyanwu JN, Williams O, Sautter CL, Kasirye P, Hume H, Opoka RO, Latham T, Ndugwa C, Ware RE, John CC. Novel Use of Hydroxyurea in an African Region With Malaria: Protocol for a Randomized Controlled Clinical Trial. JMIR Res Protoc. 2016 Jun 23;5(2):e110. doi: 10.2196/resprot.5599.

    PMID: 27339303DERIVED

MeSH Terms

Conditions

Anemia, Sickle CellMalaria

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, CongenitalAnemia, HemolyticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesHemoglobinopathiesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesProtozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

UreaAmidesOrganic Chemicals

Results Point of Contact

Title
Dr Chandy John
Organization
Indiana University
chjohn@iu.edu
317-274-8940

Study Officials

  • Chandy C. John, M.D.

    Indiana University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Pediatrics, Medicine, Microbiology and Immunology

Study Record Dates

First Submitted

October 22, 2013

First Posted

November 5, 2013

Study Start

September 1, 2014

Primary Completion

October 1, 2016

Study Completion

November 1, 2017

Last Updated

December 4, 2018

Results First Posted

October 1, 2018

Record last verified: 2018-11

Data Sharing

IPD Sharing
Will not share

Locations

UG(1)