Nitric Oxide Inhalation to Treat Sickle Cell Pain Crises

Status:	Completed
Conditions:	Anemia
Therapuetic Areas:	Hematology
Healthy:	No
Age Range:	10 - Any
Updated:	12/3/2017
Start Date:	October 2004
End Date:	December 2008

A Prospective, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of Nitric Oxide for Inhalation in the Acute Treatment of Sickle Cell Pain Crisis

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.

We found this trial at

sites

National Institutes of Health Clinical Center, 9000 Rockville Pike

9000 Rockville Pike
Bethesda, Maryland 20892

from

Bethesda, MD