Nitric Oxide Inhalation to Treat Sickle Cell Pain Crises

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
INO Therapeutics
ClinicalTrials.gov Identifier:
NCT00094887
First received: October 28, 2004
Last updated: August 10, 2011
Last verified: August 2011
  Purpose

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 Intervention Phase
Anemia, Sickle Cell
Drug: Nitric Oxide
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by INO Therapeutics:

Primary Outcome Measures:
  • Time to Resolution of Vaso-occlusive Pain Crisis (VOC) [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]

    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:
  • Vital Signs [ Time Frame: At baseline, then every hour for the first 8 hours of therapy, followed by every 4 hours of therapy. ] [ Designated as safety issue: No ]
  • Methemoglobin Levels [ Time Frame: at 2,4,6, and 8 hours after the start of therapy and then every 24 hours while on therapy. ] [ Designated as safety issue: Yes ]
  • Need for Analgesics [ Time Frame: baseline and throughout treatment. ] [ Designated as safety issue: No ]
  • Blood Chemistry Levels [ Time Frame: every 24 hours for the first 5 days after start of treatment. ] [ Designated as safety issue: No ]
  • Length of Hospitalization From Admissions Defined by the Time of the Discharge Order is Written [ Time Frame: study duration ] [ Designated as safety issue: No ]
  • Rate of Acute Chest Syndrome/Pneumonia Requiring Blood Transfusion [ Time Frame: study duration ] [ Designated as safety issue: No ]

Enrollment: 150
Study Start Date: October 2004
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Ages Eligible for Study:   10 Years and older
Genders Eligible for Study:   Both
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00094887

Locations
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
INO Therapeutics
Investigators
Study Director: James Baldassarre, MD INO Therapeutics
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: James Baldassarre, INO Therapeutics
ClinicalTrials.gov Identifier: NCT00094887     History of Changes
Obsolete Identifiers: NCT00652535
Other Study ID Numbers: 050019, INOT 36, 05-H-0019
Study First Received: October 28, 2004
Results First Received: December 4, 2009
Last Updated: August 10, 2011
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Anemia
Anemia, Sickle Cell
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
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Cardiovascular Agents
Protective Agents

ClinicalTrials.gov processed this record on April 16, 2014