Hydroxyurea and Transfusion

Sickle Cell Disease Clinical Trial

— HAT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03644953
• Other study ID #: Pro00010541
• Status: Completed
• Phase: Phase 2
• Start date: October 30, 2018
• Est. completion date: July 1, 2021

Study information

• Verified date: October 2021
• Source: Children's National Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: July 1, 2021
• Est. primary completion date: July 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 24 Years

Eligibility

Inclusion Criteria:

1. Diagnosis of SCA (Hb SS or Sß0 thalassemia).

2. 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:

1. 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.

2. Treatment with hydroxyurea in the 12 months prior to study enrollment.

3. Abnormal initial laboratory values (temporary exclusions):

1. Absolute neutrophil count <1.5 x 10^9/L

2. Platelet count <100 x 10^9/L

3. Serum creatinine more than twice upper limit for age

4. Pregnancy or unwillingness to use a medically acceptable form of contraception if sexually active.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

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.

Locations

Country	Name	City	State
United States	Children's National Health System	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Children's National Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recruitment ratio	number of participants who enroll on the study / total number of eligible subjects	1 year
Primary	Retention ratio	number participants who remain on study 1 year after HAT target dose / total number enrolled participants	1 year
Primary	Hydroxyurea adherence ratio	(hydroxyurea amount dispensed - amount returned) / prescribed amount between visits	1 year
Secondary	Proportion of subjects who develop an hemoglobin (Hb) S >45% AND an Hb >11.0 g/dL	incidence of above safety event will be monitored closely throughout the trial	1 year
Secondary	Volume of red blood cells transfused per patient weight	measure to evaluate the transfusion requirement of HAT	1 year