Nitric Oxide Inhalation to Treat Sickle Cell Pain Crises
Nitric Oxide Inhalation to Treat Sickle Cell Pain Crises
This study will examine whether nitric oxide (NO) gas can reduce the time it takes for pain
 to go away in patients who are in sickle cell crisis. NO is important in regulating blood
 vessel dilation, and consequently, blood flow. The gas is continuously produced by cells that
 line the blood vessels. It is also transported from the lungs by hemoglobin in red blood
 cells.

 Patients 10 years of age or older with sickle cell disease (known SS, S-beta-thalassemia or
 other blood problems causing sickle cell disease) may be eligible for this study. Patients
 whose disease is due to hemoglobin (Hgb) SC are excluded. Candidates are screened with blood
 tests and a chest x-ray to look at the lungs and heart.

 Participants are admitted to the hospital in a pain crisis. They are evaluated and then
 randomly assigned to receive one of two treatments: 1) standard treatment plus NO, or 2)
 standard treatment plus placebo. The placebo used in this study is nitrogen, a gas that makes
 up most of the air we breathe and is not known to help in sickle cell disease.

 For the first 8 hours of the study, patients receive placebo or NO through a facemask. The
 mask may be taken off for 5 minutes every hour and for not more than 20 minutes to eat a
 meal. After the first 8 hours, the gas is delivered through a nasal cannula (small plastic
 tubing that rests under the nose) that may be taken off only while showering or using the
 restroom. Patients are questioned about the severity of their pain when they start the study
 and then every few hours while they are in the hospital. Their vital signs (temperature,
 breathing rate, and blood pressure) and medicines are checked. Patients will breathe the gas
 for a maximum of 3 days, but will stay hospitalized until the patient feels well enough to go
 home. Patients are followed up about 1 month after starting the study by a return visit to
 the hospital or by a phone call.
The object of this study is to determine the safety and efficacy of nitric oxide for
 inhalation in the treatment of vaso-occlusive pain crisis (VOC) in patients with sickle cell
 disease. The study population will include patients with sickle cell disease (SS,
 S-beta-Thalassemia) presenting with vaso-occlusive pain crisis. Patients will be administered
 either placebo or inhaled nitric oxide to see if the experimental agent, inhaled nitric
 oxide, can reduce the time it takes for resolution of the vaso-occlusive crisis.
Inclusion Criteria:

 Each subject must meet all of the following inclusion criteria during the screening process
 in order to participate in the study:

 -  Patient must have a diagnosis of SCD (known SS, S-Beta-thalassemia or other
 hemoglobinopathies causing sickle cell disease). Patients with disease due to Hgb SC
 are not permitted.

 -  Must present to the ED/EC or other appropriate unit in VOC.

 -  Greater than or equal to 10 years old.

 -  Written informed consent/assent has been obtained.

 Exclusion Criteria:

 Subjects meeting any of the following criteria during baseline evaluation will be excluded
 from entry into the study:

 -  Exposure to therapeutic nitric oxide within the past 12 hours.

 -  Patient has received sildenafil or other phosphodiesterase 5 inhibitors, therapeutic
 L-arginine, nitroprusside or nitroglycerine within the past 12 hours.

 -  Patient has received previous ED/EC or other appropriate unit treatment for a
 vaso-occlusive crisis less than 48 hours or hospitalization less than 14 days ago
 (patients transferred directly from another ED or clinic may be enrolled).

 -  Patient has visited the ED/EC or other appropriate unit greater than 10 times in the
 past year having a vaso-occlusive crisis.

 -  Patients presenting with clinically diagnosed bacterial infection (e.g.,
 osteomyelitis, pneumonia, sepsis or meningitis).

 -  Patients who are currently enrolled in any other investigational drug study except for
 hydroxyurea studies.

 -  Pregnant women (urine HCG + )/ nursing mothers.

 -  Patients who have received an exchange transfusion (not simple transfusion) in the
 last 30 days or are on a chronic simple or exchange transfusion program.

 -  Suspected splenic sequestration.

 -  Acute chest syndrome or pneumonia: Abnormal new pulmonary infiltrate (alveolar
 infiltration and not atelectasis) and one or more pulmonary signs and/or symptoms
 (fever, rales, wheezing, cough, shortness of breath, retractions).

 -  Previous participation in this study.