Pulmonary Hypertension, Sickle Cell Disease
Conditions
Keywords
Sickle Cell Disease, Pulmonary Hypertension
Brief summary
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
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.
Interventions
DRUGHydroxyurea
20 mg/kg/day and dose escalating every 2 months until maximum tolerated dose.
Sponsors
Ann & Robert H Lurie Children's Hospital of Chicago
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 25 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tricuspid Regurgitant Jet Velocity | 6 and 12 months after HU therapy begins | Primary outcome measure was tricuspid regurgitant jet velocity (TRJV) by echocardiogram after 6 and 12 months of hydroxyurea therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compliance | Throughout study | 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). |
Countries
United States
Participant flow
Recruitment details
This study is currently closed to patient accrual at all sites due to poor enrollment, including Children's Memorial Hospital, Washington University, Johns Hopkins and the Medical College of Wisconsin. The FDA was notified in 2010, and the IND was removed for this study.
Participants by arm
| Arm | Count |
|---|---|
| Hydroxyurea Hydroxyurea : 20 mg/kg/day and dose escalating every 2 months until maximum tolerated dose. | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Hydroxyurea |
|---|---|
| Age, Categorical <=18 years | 6 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Tricuspid Regurgitant Jet Velocity
Primary outcome measure was tricuspid regurgitant jet velocity (TRJV) by echocardiogram after 6 and 12 months of hydroxyurea therapy.
Time frame: 6 and 12 months after HU therapy begins
Population: Study was terminated and 0 participants were analyzed.
Secondary
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).
Time frame: Throughout study