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Nitric Oxide Inhalation to Treat Sickle Cell Pain Crises

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ClinicalTrials.gov Identifier: NCT00094887
Recruitment Status : Completed
First Posted : October 28, 2004
Results First Posted : April 23, 2010
Last Update Posted : February 5, 2020
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Mallinckrodt

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.

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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: Inhaled Nitric Oxide
Participants receive Inhaled nitric oxide (INO)
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: Placebo
Participants receive Nitrogen gas
Drug: Placebo
Nitrogen gas will be delivered in the same manor as the experimental drug.




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

    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.


Secondary Outcome Measures :
  1. Length of Hospitalization [ Time Frame: within 40 days ]
    Length of hospitalization is defined as the length of time from admission to discharge order

  2. Number of Participants Discharged to Home Within the First 24 Hours [ Time Frame: within 24 hours ]
  3. Total Dose of Opioids Received [ Time Frame: within 8 hours and within 40 days ]
    The total dose (mg) of opioid medications received during the trial

  4. Number of Participants With Acute Chest Syndrome/Pneumonia Requiring Blood Transfusion [ Time Frame: within 40 days ]
    Number of participants who required a blood transfusion before discharge because of acute chest syndrome/pneumonia

  5. Number of Participants Readmitted to Hospital Within 30 Days After Discharge [ Time Frame: during first 24 hours and during 30 day follow-up ]
    The number of participants readmitted to the hospital for any reason within 30 days after discharge



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

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 ClinicalTrials.gov identifier (NCT number): NCT00094887


Locations
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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
Sponsors and Collaborators
Mallinckrodt
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Study Director: James Baldassarre, MD Mallinckrodt
Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Mallinckrodt
ClinicalTrials.gov Identifier: NCT00094887    
Obsolete Identifiers: NCT00652535
Other Study ID Numbers: 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: February 5, 2020
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Mallinckrodt:
Blood Flow
Nitric Oxide
Pain Crisis
Sickle Cell Anemia
Vaso-Occlusive Crisis
Sickle Cell Disease
SCD
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
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
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Gasotransmitters
Protective Agents