Nitric Oxide Inhalation to Treat Sickle Cell Pain Crises

NCT ID: NCT00094887

Last Updated: 2020-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-10-31
• Study Completion Date: 2008-12-31

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.

Conditions

Anemia, Sickle Cell

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Inhaled Nitric Oxide

Participants receive Inhaled nitric oxide (INO)

Group Type: EXPERIMENTAL

Nitric Oxide

Intervention Type: DRUG

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.

Placebo

Participants receive Nitrogen gas

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Nitrogen gas will be delivered in the same manor as the experimental drug.

Interventions

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.

Intervention Type: DRUG

Placebo

Nitrogen gas will be delivered in the same manor as the experimental drug.

Intervention Type: DRUG

Other Intervention Names

INOmax

Eligibility Criteria

Inclusion Criteria

• 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.

• Minimum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Mallinckrodt

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James Baldassarre, MD

Role: STUDY_DIRECTOR

Mallinckrodt

Locations

University of Alabama

Birmingham, Alabama, United States

Children's Hospital Oakland

Oakland, California, United States

Colorado Sickle Cell Treatement and Research Center

Aurora, Colorado, United States

Howard University Hospital

Washington D.C., District of Columbia, United States

Johns Hopkins University

Baltimore, Maryland, United States

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Childrens Hospital, Boston

Boston, Massachusetts, United States

Case Western Reserve University Hospital

Cleveland, Ohio, United States

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Childrens Hospital, Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 1302470 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21364138 (View on PubMed)

Related Links

https://www.ncbi.nlm.nih.gov/m/pubmed/1302470/

NIH Clinical Center Detailed Web Page

Other Identifiers

05-H-0019

Identifier Type: REGISTRY

Identifier Source: secondary_id

INOT 36

Identifier Type: -

Identifier Source: org_study_id

NCT00652535

Identifier Type: -

Identifier Source: nct_alias