Hydroxyurea for Children and Young Adults With Sickle Cell Disease and Pulmonary Hypertension

Study Overview
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Brief Summary
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The goal of this study is to test the hypothesis that hydroxyurea is effective for the specific treatment of secondary pulmonary hypertension found on screening in children and young adults with sickle cell disease.

Detailed Description
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Increasing evidence suggests that pulmonary hypertension, defined by an elevated tricuspid regurgitant jet velocity (TRJV) on echocardiogram, is a major cause of morbidity and mortality in adults with sickle cell disease (SCD). However, both the prevalence and optimal treatment of pulmonary hypertension in children and young adults with SCD are unknown. We hypothesize that short term therapy with hydroxyurea will decrease TRJV in children and young adults with pulmonary hypertension found on screening. Patients eligible for treatment will have had evidence of pulmonary hypertension on at least 2 screening echocardiograms. Baseline laboratory tests will be obtained and other causes of secondary pulmonary hypertension will be excluded prior to initiation of treatment. Patients will be treated with hydroxyurea according to a standard dose escalation schedule for a total of 12 months. A clinic visit will be required every 2 months and standard screening for toxicity will be performed monthly. There will be an interim analysis of the primary outcome at 6 months following therapy.

Official Title
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A Pilot Study of Hydroxyurea for the Treatment of Pulmonary Hypertension in Children and Young Adults With Sickle Cell Disease

Conditions
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Sickle Cell Disease, Pulmonary Hypertension

Intervention / Treatment
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* Drug: Hydroxyurea


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 10 and 25 years old Sickle cell disease with hemoglobin SS, SC or S-B^0 thalassemia confirmed on hemoglobin electrophoresis Tricuspid regurgitant jet velocity (TRJV) equal to or greater than 2.5 m/sec on 2 baseline Doppler echocardiograms at least 3 months apart Exclusion Criteria: Patients already being treated with hydroxyurea Patients on a chronic transfusion protocol Patients with evidence of hepatic (alanine aminotransferase [ALT] equal to or greater than 2 SD above normal) or renal dysfunction (creatinine [Cr] equal to or greater than 2 SD above normal) Patients who are pregnant Patients with documented causes of severe pulmonary hypertension other than from SCD

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxyurea<br> | Drug: Hydroxyurea<br>* 20 mg/kg/day and dose escalating every 2 months until maximum tolerated dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tricuspid Regurgitant Jet Velocity | Primary outcome measure was tricuspid regurgitant jet velocity (TRJV) by echocardiogram after 6 and 12 months of hydroxyurea therapy. | 6 and 12 months after HU therapy begins | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compliance | Secondary outcome measures included compliance; laboratory measures of therapy-related toxicity; laboratory biomarkers for hemolysis, oxidative stress and endothelial injury; and quality of life measures by Child Health Questionnaire (CHQ). | Throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle Cell Disease, Pulmonary Hypertension