During the study period, 99 patients who were seen at The Johns Hopkins Hospital in Baltimore were identified as having both sickle cell disease and influenza (89 with seasonal influenza and 10 with H1N1 influenza). Clinical symptoms, such as fever, cough, and runny nose, were similar between the two groups, although those with H1N1 influenza were at an estimated three-fold increased risk for life-threatening complications, such as acute chest syndrome (a severe lung illness), and nine times more likely to require intensive care, such as ventilator support.
"Our findings underscore that receiving a vaccination against H1N1 influenza, in addition to seasonal influenza, is extremely important for the health and safety of children and young adults with sickle cell disease," said lead author John J. Strouse, MD, PhD, Assistant Professor of Pediatrics and Medicine at The Johns Hopkins University School of Medicine in Baltimore.
Dr. Strouse will present this study in an oral session on Monday, December 7, at 8:15 a.m. in Room 220-222.
Safety and Efficacy of Sildenafil Therapy for Doppler-Defined Pulmonary Hypertension in Patients With Sickle Cell Disease: Preliminary Results of the Walk-PHaSST Clinical Trial [Abstract #571]
As patients with sickle cell disease have a high rate of hemolysis (red blood cell destruction), excessive amounts of hemoglobin are released into the blood stream that react with and destroy nitric oxide, a critical regulator that dilates blood vessels and inhibits clotting. This can lead to pulmonary hypertension, or abnormally high blood pressure in the arteries of lungs that also affects the heart. Approximately 10 to 30 percent of patients with sickle cell disease are suspected to have this life-threatening condition.
While the oral drug sildenafil (known as Revatio-) is approved to treat pulmonary arterial hypertension, it is unknown whether it is a safe and effective treatment for pulmonary hypertension in those with sickle cell disease. Therefore, a 16-week, double-blind clinical trial, known as the Walk-PHaSST study (treatment of Pulmonary Hypertension and Sickle cell disease with Sildenafil Therapy) was conducted in 10 medical centers in the United States and United Kingdom to test this application in adults and children over 12 years of age with sickle cell disease.
Before starting treatment, potential study participants were given baseline tests, including a Doppler echocardiogram and a six-minute walk test to measure heart and lung function. Seventy-four patients who had a tricuspid regurgitant jet velocity (TRV) of greater than or equal to 2.7 m/s (a sign of suspected high pulmonary blood pressure) and a six-minute walking distance of only 150-500 meters (reflecting decreased exercise capacity) were included in the study. The researchers then randomly assigned the study participants into two groups of 37 patients each. Half of the patients were treated with sildenafil at escalating doses from 20, 40, and 80 mg three times per day, and the other half received a placebo three times per day. In previous studies of patients with primary pulmonary hypertension, the highest dose of sildenafil (80 mg) had the greatest effect on blood circulation; however, to monitor for possible adverse effects associated with escalating doses, the sildenafil doses in this study were increased slowly, with dose increases made every four weeks.
The study was prematurely stopped when a significant number of the patients in the sildenafil treatment arm (46 percent) began experiencing serious side effects (primarily sickle cell pain crises requiring hospitalization), compared with only 22 percent of those in the placebo arm. Headache and blurred vision, which were expected side effects of sildenafil, were also experienced. The patients in the sildenafil group had more headaches (27 percent versus 14 percent) and more blurred vision (11 percent versus 3 percent) than the placebo group.
Prior to stopping the study, 33 patients had completed the 16-week assessment and were found to have no change in TRV value or in the walking distance test. On pain questionnaires, patients on the sildenafil treatment also reported worsening pain during walking and less enjoyment of life when compared to the patients on placebo.
"Although sildenafil is approved by the U.S. Food and Drug Administration and by the European Medicines Agency for patients with pulmonary arterial hypertension, the Walk-PHaSST study was prematurely stopped for safety concerns. However, these preliminary data should not be interpreted as implying that sildenafil may not be efficacious and safe in select sickle cell patients with documented pulmonary hypertension who are at low risk for vaso-occlusive events," said lead study author Mark Gladwin, MD, Chief of the Division of Pulmonary, Allergy, and Critical Care Medicine and Director of the Vascular Medicine Institute at the University of Pittsburgh Medical Center. "Further investigations are critically needed to find a safe and effective treatment for this patient population at high risk for death from this debilitating condition."
Dr. Gladwin will present this study in an oral session on Monday, December 7, at 2:45 p.m. in Room 220-222.
Source: American Society of Hematology