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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||A Prospective, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of Nitric Oxide for Inhalation in the Acute Treatment of Sickle Cell Pain Crisis|
- Time to Resolution of Vaso-occlusive Pain Crisis (VOC) [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
Time to VOC resolution was defined by:
Pain relief - Visual Analog Scale (VAS) pain scores of 6 or less, (6 as worst and 0 as best) Freedom from parenteral narcotic use, Ability to walk unless the subject was not able to walk for any reason other than acute VOC prior to the onset of crisis, Subject and/or family's belief that the painful crisis could be managed at home with or without oral analgesic use, and the physician concurred with that assessment.
- Vital Signs [ Time Frame: At baseline, then every hour for the first 8 hours of therapy, followed by every 4 hours of therapy. ] [ Designated as safety issue: No ]
- Methemoglobin Levels [ Time Frame: at 2,4,6, and 8 hours after the start of therapy and then every 24 hours while on therapy. ] [ Designated as safety issue: Yes ]
- Need for Analgesics [ Time Frame: baseline and throughout treatment. ] [ Designated as safety issue: No ]
- Blood Chemistry Levels [ Time Frame: every 24 hours for the first 5 days after start of treatment. ] [ Designated as safety issue: No ]
- Length of Hospitalization From Admissions Defined by the Time of the Discharge Order is Written [ Time Frame: study duration ] [ Designated as safety issue: No ]
- Rate of Acute Chest Syndrome/Pneumonia Requiring Blood Transfusion [ Time Frame: study duration ] [ Designated as safety issue: No ]
|Study Start Date:||October 2004|
|Study Completion Date:||December 2008|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
Inhaled nitric oxide
Drug: Nitric Oxide
Nitric oxide will be delivered for 4 hours at 80 ppm through a face mask. The dose will then be reduced to 40 ppm for 4 hours. After a total of 8 hours of treatment through face mask, the patient will get 6 mL/puls/breath of NO at 800 ppm or 3 m//pulse/breath, depending on patient weight.
Other Name: INOmax
Placebo Comparator: 2
Nitrogen gas will be delivered in the same manor as the experimental drug.
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.
|United States, Alabama|
|University of Alabama|
|Birmingham, Alabama, United States, 35294|
|United States, California|
|Children's Hospital Oakland|
|Oakland, California, United States, 94609-1809|
|United States, Colorado|
|Colorado Sickle Cell Treatement and Research Center|
|Aurora, Colorado, United States, 80045|
|United States, District of Columbia|
|Howard University Hospital|
|Washington, District of Columbia, United States, 20060|
|United States, Maryland|
|Johns Hopkins University|
|Baltimore, Maryland, United States, 21205|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|United States, Massachusetts|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States, 02115|
|Childrens Hospital, Boston|
|Boston, Massachusetts, United States, 02115|
|United States, Ohio|
|Case Western Reserve University Hospital|
|Cleveland, Ohio, United States, 44106-2602|
|United States, Pennsylvania|
|St. Christopher's Hospital for Children|
|Philadelphia, Pennsylvania, United States, 19134|
|Childrens Hospital, Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15213-2583|
|Study Director:||James Baldassarre, MD||INO Therapeutics|