Working... Menu

Nitric Oxide Inhalation to Treat Sickle Cell Pain Crises

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00094887
Recruitment Status : Completed
First Posted : October 28, 2004
Results First Posted : April 23, 2010
Last Update Posted : December 2, 2017
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Anemia, Sickle Cell Drug: Nitric Oxide Drug: Placebo Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, 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
Study Start Date : October 2004
Actual Primary Completion Date : December 2008
Actual Study Completion Date : December 2008

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 1
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
Drug: Placebo
Nitrogen gas will be delivered in the same manor as the experimental drug.

Primary Outcome Measures :
  1. Time to Resolution of Vaso-occlusive Pain Crisis (VOC) [ Time Frame: Up to 30 days ]

    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.

Secondary Outcome Measures :
  1. Vital Signs [ Time Frame: At baseline, then every hour for the first 8 hours of therapy, followed by every 4 hours of therapy. ]
  2. Methemoglobin Levels [ Time Frame: at 2,4,6, and 8 hours after the start of therapy and then every 24 hours while on therapy. ]
  3. Need for Analgesics [ Time Frame: baseline and throughout treatment. ]
  4. Blood Chemistry Levels [ Time Frame: every 24 hours for the first 5 days after start of treatment. ]
  5. Length of Hospitalization From Admissions Defined by the Time of the Discharge Order is Written [ Time Frame: study duration ]
  6. Rate of Acute Chest Syndrome/Pneumonia Requiring Blood Transfusion [ Time Frame: study duration ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   10 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00094887

Layout table for location information
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, D.C., 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
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Layout table for investigator information
Study Director: James Baldassarre, MD Mallinckrodt

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Mallinckrodt Identifier: NCT00094887     History of Changes
Obsolete Identifiers: NCT00652535
Other Study ID Numbers: 050019, INOT 36
05-H-0019 ( Registry Identifier: NIH )
First Posted: October 28, 2004    Key Record Dates
Results First Posted: April 23, 2010
Last Update Posted: December 2, 2017
Last Verified: October 2017

Keywords provided by Mallinckrodt:
Blood Flow
Nitric Oxide
Pain Crisis
Sickle Cell Anemia
Vaso-Occlusive Crisis
Sickle Cell Disease

Additional relevant MeSH terms:
Layout table for MeSH terms
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hematologic Diseases
Genetic Diseases, Inborn
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Protective Agents