Sildenafil Therapy for Pulmonary Hypertension and Sickle Cell Disease

Sickle Cell Disease Clinical Trial

Official title: Treatment of Pulmonary Hypertension and Sickle Cell Disease With Sildenafil Therapy

Status Terminated

Clinical Trial Summary

This study will examine whether the drug sildenafil can lower blood pressure in the pulmonary artery (the blood vessel that leads from the heart to the lungs) in patients with sickle cell disease and pulmonary hypertension (high blood pressure in the lungs). It will see if this treatment can reduce disease complications, such as shortness of breath, pain crisis, pneumonia, and increase survival.

Patients 12 years of age and older with sickle cell disease and pulmonary hypertension may be eligible for this study. Participants are randomly assigned to receive sildenafil or placebo (sugar pill) for 16 weeks. Before starting treatment, patients have baseline studies, including a pregnancy test for females of childbearing age; a chest x-ray; pulmonary function tests to measure how much air the patient can breathe in and out; an echocardiogram (heart ultrasound); a 6-minute walk test to measure exercise capacity; a quality-of-life assessment and a pain inventory. Patients with moderate to severe pulmonary hypertension undergo heart catheterization to evaluate the severity of hypertension before beginning sildenafil therapy.

During treatment, patients are monitored with the following:

• Blood tests: weeks 6, 10 and 16.

• Echocardiogram: weeks 6 and 16.

• 6-minute walk test: weeks 6, 10 and 16.

• Measurements of weight, blood pressure and heart rate: weeks 6, 10 and 16.

• Pregnancy test for women of childbearing age: weeks 6, 10 and 16.

• Pain questionnaire once a day for a week: weeks 6 and 1.0

• Quality-of-life questionnaire: week 16.

• Heart catheterization: week 16 for patients with moderate to severe hypertension.

At the end of the 16-week period, patients may opt to continue to receive sildenafil and monitoring in an open-label phase of the study for up to 1 year.

Clinical Trial Description

Sickle cell disease (SCD) is an autosomal recessive disorder and the most common genetic disease affecting African-Americans. Approximately 0.15 percent of African-Americans are homozygous for sickle cell disease, and 8 percent have sickle cell trait. Acute pain crisis, acute chest syndrome (ACS), and pulmonary hypertension are common complications of sickle cell anemia. Pulmonary hypertension (PH) has now been identified as a marker of mortality in adults with sickle cell disease. Sildenafil has been proven beneficial in pulmonary hypertension (PH) and recent phase I/II studies from the intramural National Institutes of Health (NIH) suggest it is well tolerated and efficacious in the SCD population. Furthermore, a number of recent studies have suggested that nitric oxide (NO) based therapies may have a favorable impact on sickle red cells at the molecular level and could improve the abnormal microvascular perfusion that is characteristic of sickle cell anemia.

The project has 3 distinct components:

1. Screening Phase. Approximately 1000 subjects with sickle cell disease will be screened. Assessments will include historical and laboratory data, Doppler echocardiogram, 6-minute walk test, plasma/serum, and DNA for banking.

2. Main Interventional Trial. The randomized, double-blind, placebo controlled phase is designed to determine the effects of 16 weeks of Sildenafil therapy on exercise endurance, cardiopulmonary hemodynamic parameters and symptoms in this patient population. The open-label follow-up phase is designed to provide up to an additional year of Sildenafil therapy to subjects who completed the randomized, double-blind phase.

3. Observational Follow-up Study. Screened patients who do not qualify for participation in the main interventional trial may be contacted every 6-12 months for up to 3 years to assess major disease-related complications, including mortality. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension
• Sickle Cell Disease

• NCT number: NCT00492531
• Study type: Interventional
• Source: National Heart, Lung, and Blood Institute (NHLBI)
• Status: Terminated
• Phase: Phase 2
• Start date: June 2007
• Completion date: October 2009