Cardiopulmonary Function Assessment and NO-Based Therapies for Patients With Hemolysis-Associated Pulmonary Hypertension
Mots clés
Abstrait
La description
Sickle cell anemia is an autosomal recessive disorder and the most common genetic disease affecting African-Americans. Approximately 0.15% of African-Americans are homozygous for sickle cell disease, and 8% have sickle cell trait. Acute pain crisis, acute chest syndrome (ACS), and secondary pulmonary hypertension are common complications of sickle cell anemia. Pulmonary hypertension has now been identified as a major cause of death in adults with sickle cell disease. Similarly, pulmonary hypertension has been identified as a chronic complication of hemolytic disorders such as thalassemia, hereditary spherocytosis and paroxysmal nocturnal hemoglobinuria. Sildenafil has been proposed as a possible therapy for both primary and secondary pulmonary hypertension and recent phase I/II studies from the intramural NIH suggest it is well tolerated and efficacious in this population. Furthermore, a number of recent studies have suggested that 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.
This clinical trial is designed with three major objectives: 1) to assess cardiopulmonary function in patients with sickle cell disease and thalassemia with and without pulmonary hypertension, 2) to determine the relative acute vasodilatory effects of sildenafil, and inhaled NO in patients with hemolysis-associated pulmonary hypertension and 3) to determine the chronic effects of the addition of inhaled NO on pulmonary hemodynamics and functional capacity in patients with hemolysis-associated pulmonary hypertension chronically treated with sildenafil.
Rendez-vous
| Dernière vérification: | 12/06/2015 |
| Première soumission: | 07/12/2006 |
| Inscription estimée soumise: | 07/12/2006 |
| Première publication: | 07/13/2006 |
| Dernière mise à jour soumise: | 09/23/2019 |
| Dernière mise à jour publiée: | 09/24/2019 |
| Date de début réelle de l'étude: | 07/08/2006 |
| Date d'achèvement primaire estimée: | 03/09/2010 |
| Date estimée d'achèvement de l'étude: | 03/09/2010 |
Condition ou maladie
Intervention / traitement
Drug: Nitric Oxide/INP Pulse Delivery
Drug: Nitric Oxide/INO Pulse Delivery
Phase
Critère d'éligibilité
| Âges éligibles aux études | 18 Years À 18 Years |
| Sexes éligibles à l'étude | All |
| Accepte les bénévoles en santé | Oui |
| Critères | - INCLUSION CRITERIA - Males or females, 18 years of age or older. - Diagnosis of sickle cell disease (electrophoretic documentation of SS, SC, or S thalassemia genotype is required) or thalassemia. - For female subjects, on a reliable method of birth control or not physically able to bear children. For Stage II: - Mild to severe pulmonary hypertension with mean pulmonary artery pressure greater than 25 mm Hg at rest or greater than 30 mm Hg during exercise, measured by pulmonary artery catheterization. - Pulmonary artery wedge pressure or left ventricular end-diastolic pressure less than or equal to 18 mm Hg or gradient between pulmonary artery diastolic pressure and wedge pressure greater than 8 mm Hg or echocardiographic criteria to exclude left ventricular dysfunction. - For female subjects, on a reliable method of birth control or not physically able to bear children. For Stage III: - Mild to severe pulmonary hypertension with mean pulmonary artery pressure greater than 25 mm Hg at rest or greater than 30 mm Hg during exercise, measured by pulmonary artery catheterization in patients on chronic sildenafil therapy for at least three months. Patients receiving combination drug therapy with other drugs (e.g., endothelin antagonists, prostacyclins) are allowed to participate in stage III as long as sildenafil is one of the components of the combination regimen. - Pulmonary artery wedge pressure or left ventricular end-diastolic pressure less than or equal to 18 mm Hg or gradient between pulmonary artery diastolic pressure and wedge pressure greater than 8 mm Hg or echocardiographic criteria to exclude left ventricular dysfunction. - Must be on chronic sildenafil therapy on a stable dose for at least three months. - For female subjects, on a reliable method of birth control or not physically able to bear children. EXCLUSION CRITERIA For Stage I - Current pregnancy or lactation. - Any condition that in the opinion of the study investigators would adversely affect the outcome of the study or the safety of the volunteer. For Stage II and III: - Current pregnancy or lactation. - Any of the following medical conditions 1. Stroke within the last six weeks. 2. History of sustained priapism requiring medical or surgical treatment, unless currently impotent or on exchange transfusion therapy, within two years. |
Résultat
Mesures des résultats primaires
1. To assess cardiopulmonary function in patients with sickle cell disease and thalassemia with and without pulmonary hypertension. [undefined]
Mesures des résultats secondaires
1. To determine the relative acute vasodilatory effects of sildenafil, and inhaled NO in patients with hemolysis-associated pulmonary hypertension. [undefined]
