Nitric Oxide Inhalation to Treat Sickle Cell Pain Crises
A Prospective, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of Nitric Oxide for Inhalation in the Acute Treatment of Sickle Cell Pain Crisis
2 other identifiers
interventional
150
1 country
11
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Oct 2004
Typical duration for phase_2
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2004
CompletedFirst Submitted
Initial submission to the registry
October 28, 2004
CompletedFirst Posted
Study publicly available on registry
October 28, 2004
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2008
CompletedResults Posted
Study results publicly available
April 23, 2010
CompletedFebruary 5, 2020
October 1, 2017
4.2 years
October 28, 2004
December 4, 2009
January 17, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Time to Vaso-occlusive Pain Crisis (VOC) Resolution
VOC resolution was defined by all of the following conditions: * 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.
within 30 days
Secondary Outcomes (5)
Length of Hospitalization
within 40 days
Number of Participants Discharged to Home Within the First 24 Hours
within 24 hours
Total Dose of Opioids Received
within 8 hours and within 40 days
Number of Participants With Acute Chest Syndrome/Pneumonia Requiring Blood Transfusion
within 40 days
Number of Participants Readmitted to Hospital Within 30 Days After Discharge
during first 24 hours and during 30 day follow-up
Study Arms (2)
Inhaled Nitric Oxide
EXPERIMENTALParticipants receive Inhaled nitric oxide (INO)
Placebo
PLACEBO COMPARATORParticipants receive Nitrogen gas
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mallinckrodtlead
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
Study Sites (11)
University of Alabama
Birmingham, Alabama, 35294, United States
Children's Hospital Oakland
Oakland, California, 94609-1809, United States
Colorado Sickle Cell Treatement and Research Center
Aurora, Colorado, 80045, United States
Howard University Hospital
Washington D.C., District of Columbia, 20060, United States
Johns Hopkins University
Baltimore, Maryland, 21205, United States
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Childrens Hospital, Boston
Boston, Massachusetts, 02115, United States
Case Western Reserve University Hospital
Cleveland, Ohio, 44106-2602, United States
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134, United States
Childrens Hospital, Pittsburgh
Pittsburgh, Pennsylvania, 15213-2583, United States
Related Publications (2)
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.
PMID: 1302470BACKGROUNDGladwin 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.
PMID: 21364138DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Information Call Center
- Organization
- Mallinckrodt Pharmaceuticals
Study Officials
- STUDY DIRECTOR
James Baldassarre, MD
Mallinckrodt
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 28, 2004
First Posted
October 28, 2004
Study Start
October 1, 2004
Primary Completion
December 1, 2008
Study Completion
December 1, 2008
Last Updated
February 5, 2020
Results First Posted
April 23, 2010
Record last verified: 2017-10
Data Sharing
- IPD Sharing
- Will not share