Optimizing Hydroxyurea Therapy in Children With SCA In Malaria Endemic Areas

NCT03128515 | Completed Phase 3 DMC

• 1 other identifier: 00456728
• Study Type: interventional
• Target: 187
• Locations: 1 country
• Sites: 1

Brief Summary

The Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM) study is the first placebo-controlled randomized clinical trial of hydroxyurea treatment in a malaria endemic region. NOHARM has now achieved full enrollment; all children have completed the blinded portion of the protocol and are in the open-label study treatment portion. This extension study of maximum tolerated dose (MTD), addresses the next critical set of questions about the optimal dosing and monitoring of hydroxyurea treatment for children with SCA in low-resource settings. By providing guidance about optimal hydroxyurea treatment, the NOHARM MTD Study will directly inform policies that can transform the health of African children living with SCA.

Conditions

Sickle Cell Anemia; Sickle Cell Disease; Malaria

Keywords

Hydroxyurea

Outcome Measures

Primary Outcomes (1)

• Proportion of children with average hemoglobin ≥9.0 g/dL or average HbF ≥20%

  Proportion of children who achieve either an average hemoglobin ≥9.0 g/dL or an average HbF ≥20% after 24 months on study drug

  Over 24 month period on study drug

Secondary Outcomes (11)

• Clinical malaria incidence

  Over 24 month period on study drug

• Vaso-occlusive crises

  Over 24 month period on study drug

• Incidence of severe adverse events (SAE)

  Over 24 month period on study drug

• Incidence of hematologic toxicities

  Over 24 month period on study drug

• Cerebrovascular function

  At study treatment initiation then at 12 months and 24 months after study initiation

Study Arms (2)

MTD Dose Escalation

EXPERIMENTAL

Maximum tolerated dose of Hydroxyurea, 25-30 mg/kg/day

Drug: Hydroxyurea

Fixed Dose

ACTIVE COMPARATOR

Fixed dose of Hydroxyurea, 20 mg/kg/day

Drug: Hydroxyurea

Interventions

Hydroxyurea DRUG

Administered once a day in tablet form (100mg or scored 1000mg) for 24 months

Also known as: Siklos, Hydroxycarbamide

Fixed Dose; MTD Dose Escalation

Eligibility Criteria

• Age: 24 Months - 72 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children with confirmed SCA who participated in the NOHARM study of hydroxyurea at the Mulago Hospital Sickle Cell Clinic (MHSCC), will be eligible for the MTD study after completing both 12-months of blinded study treatment and then an additional 12-months of open-label hydroxyurea for the second year of the study.
• The age range for enrollment into NOHARM, which began in 2014, was 1-4 years. Therefore, the children who will be enrolled in the follow up MTD study will be 3-6 years of age.

You may not qualify if:

• Not willing to come for all scheduled clinical visits or accept randomization

Sponsors & Collaborators

• Indiana University: lead
• Doris Duke Charitable Foundation: collaborator
• Makerere University: collaborator
• Mulago Hospital, Uganda: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator

Study Sites (1)

Mulago Hospital Sickle Cell Clinic

Kampala, Uganda

Location

Related Publications (1)

• John CC, Opoka RO, Latham TS, Hume HA, Nabaggala C, Kasirye P, Ndugwa CM, Lane A, Ware RE. Hydroxyurea Dose Escalation for Sickle Cell Anemia in Sub-Saharan Africa. N Engl J Med. 2020 Jun 25;382(26):2524-2533. doi: 10.1056/NEJMoa2000146.

  PMID: 32579813 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell; Malaria

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; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Study Officials

• Chandy C John, M.D.

  Indiana University

  PRINCIPAL INVESTIGATOR

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: March 22, 2017
• First Posted: April 25, 2017
• Study Start: July 26, 2017
• Primary Completion: April 7, 2019
• Study Completion: January 28, 2020
• Last Updated: February 20, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1)