HAT: Hydroxyurea and Transfusion

Sponsor

Children's National Research Institute (Other)

Overall Status

Completed

CT.gov ID

NCT03644953

Collaborator

(none)

Enrollment

Location

Arm

Actual Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will prospectively investigate the feasibility, safety, and transfusion requirements of adding hydroxyurea to simple chronic transfusions for patients with sickle cell anemia already on chronic transfusions.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease	Drug: Hydroxyurea	Phase 2

Detailed Description

This is a single-arm, prospective study of hydroxyurea added to simple chronic transfusions, combination treatment termed hydroxyurea and transfusion (HAT). The primary objective of the study is to determine the feasibility of HAT for patients with sickle cell anemia (SCA) currently being treated only with simple transfusions for stroke prevention. Secondary objectives include: to evaluate the safety of HAT and to determine if HAT decreases transfusion requirements in this patient population. Exploratory objectives include: to evaluate with HAT changes in pre-transfusion laboratories and biomarkers of cerebrovascular disease progression, and to describe changes on brain imaging.

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Prospective, single arm, open label study of combination hydroxyurea and simple chronic transfusion.Prospective, single arm, open label study of combination hydroxyurea and simple chronic transfusion.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Hydroxyurea and Transfusion: Pilot Study of Combination Therapy for Patients With Sickle Cell Anemia

Actual Study Start Date :

Oct 30, 2018

Actual Primary Completion Date :

Jul 1, 2021

Actual Study Completion Date :

Jul 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hydroxyurea and Transfusion (HAT) Combination hydroxyurea and simple chronic transfusion therapy	Drug: Hydroxyurea Participants will be started on hydroxyurea 20 ± 2.5 mg/kg/day in addition to continuing simple chronic transfusion every 4 weeks ± 1 week. Hydroxyurea will be dose escalated to achieve a HAT target dose (HAT-TD). Hydroxyurea will be increased by 5 mg/kg/day after 8 weeks of a dose if HAT-TD is not achieved (maximum daily dose 2,000 mg). After HAT-TD has been achieved, minor dose increases may occur if subject grows a significant amount to maintain the same mg/kg dose.

Arm

Intervention/Treatment

Experimental: Hydroxyurea and Transfusion (HAT)

Combination hydroxyurea and simple chronic transfusion therapy

Drug: Hydroxyurea

Participants will be started on hydroxyurea 20 ± 2.5 mg/kg/day in addition to continuing simple chronic transfusion every 4 weeks ± 1 week. Hydroxyurea will be dose escalated to achieve a HAT target dose (HAT-TD). Hydroxyurea will be increased by 5 mg/kg/day after 8 weeks of a dose if HAT-TD is not achieved (maximum daily dose 2,000 mg). After HAT-TD has been achieved, minor dose increases may occur if subject grows a significant amount to maintain the same mg/kg dose.

Outcome Measures

Primary Outcome Measures

Recruitment ratio [1 year]
number of participants who enroll on the study / total number of eligible subjects
Retention ratio [1 year]
number participants who remain on study 1 year after HAT target dose / total number enrolled participants
Hydroxyurea adherence ratio [1 year]
(hydroxyurea amount dispensed - amount returned) / prescribed amount between visits

Secondary Outcome Measures

Proportion of subjects who develop an hemoglobin (Hb) S >45% AND an Hb >11.0 g/dL [1 year]
incidence of above safety event will be monitored closely throughout the trial
Volume of red blood cells transfused per patient weight [1 year]
measure to evaluate the transfusion requirement of HAT

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 24 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of SCA (Hb SS or Sβ0 thalassemia).
On simple chronic transfusion therapy for stroke prevention (primary or secondary prevention) for ≥1 year with no plans to stop simple chronic transfusion in the next year.

Exclusion Criteria:

Poor adherence to simple transfusion regimen as defined by having an HbS >45% at any time in the last year AND a transfusion interval >5 weeks.
Treatment with hydroxyurea in the 12 months prior to study enrollment.
Abnormal initial laboratory values (temporary exclusions):
Absolute neutrophil count <1.5 x 10^9/L
Platelet count <100 x 10^9/L
Serum creatinine more than twice upper limit for age
Pregnancy or unwillingness to use a medically acceptable form of contraception if sexually active.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's National Health System	Washington	District of Columbia	United States	20010

Sponsors and Collaborators

Children's National Research Institute

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Robert Nickel, Principal Investigator, Children's National Research Institute

ClinicalTrials.gov Identifier:

NCT03644953

Other Study ID Numbers:

Pro00010541

First Posted:

Aug 23, 2018

Last Update Posted:

Oct 21, 2021

Last Verified:

Oct 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Robert Nickel, Principal Investigator, Children's National Research Institute

Hydroxyurea

Transfusion

Additional relevant MeSH terms:

Anemia, Sickle Cell

Hydroxyurea

Study Results

No Results Posted as of Oct 21, 2021