Clinical trial NCT00094887: Nitric Oxide Inhalation to Treat Sickle Cell Pain Crises
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia, Sickle Cell
Keywords: Blood Flow
Nitric Oxide
Pain Crisis
Sickle Cell Anemia
Vaso-Occlusive Crisis
Sickle Cell Disease
SCD
Lead sponsor: Mallinckrodt
Sponsor class: INDUSTRY
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2004-10-28
Enrollment: 150
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time to Vaso-occlusive Pain Crisis (VOC) Resolution
timeFrame: within 30 days
Secondary outcomes:
measure: Length of Hospitalization
timeFrame: within 40 days
measure: Number of Participants Discharged to Home Within the First 24 Hours
timeFrame: within 24 hours
measure: Total Dose of Opioids Received
timeFrame: within 8 hours and within 40 days
measure: Number of Participants With Acute Chest Syndrome/Pneumonia Requiring Blood Transfusion
timeFrame: within 40 days
measure: Number of Participants Readmitted to Hospital Within 30 Days After Discharge
timeFrame: during first 24 hours and during 30 day follow-up
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Oakland
country: United States
facility: Children's Hospital Oakland
state: California
city: Aurora
country: United States
facility: Colorado Sickle Cell Treatement and Research Center
state: Colorado
city: Washington
country: United States
facility: Howard University Hospital
state: District of Columbia
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Childrens Hospital, Boston
state: Massachusetts
city: Cleveland
country: United States
facility: Case Western Reserve University Hospital
state: Ohio
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Childrens Hospital, Pittsburgh
state: Pennsylvania
Study officials:
affiliation: Mallinckrodt
name: James Baldassarre, MD
role: STUDY_DIRECTOR
References:
citation: Sanders DY, Severance HW, Pollack CV Jr. Sickle cell vaso-occlusive pain crisis in adults: alternative strategies for management in the emergency department. South Med J. 1992 Aug;85(8):808-11. doi: 10.1097/00007611-199208000-00005.
citation: Gladwin MT, Kato GJ, Weiner D, Onyekwere OC, Dampier C, Hsu L, Hagar RW, Howard T, Nuss R, Okam MM, Tremonti CK, Berman B, Villella A, Krishnamurti L, Lanzkron S, Castro O, Gordeuk VR, Coles WA, Peters-Lawrence M, Nichols J, Hall MK, Hildesheim M, Blackwelder WC, Baldassarre J, Casella JF; DeNOVO Investigators. Nitric oxide for inhalation in the acute treatment of sickle cell pain crisis: a randomized controlled trial. JAMA. 2011 Mar 2;305(9):893-902. doi: 10.1001/jama.2011.235.