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

Sponsors

Lead Sponsor: Mallinckrodt

Collaborator: National Heart, Lung, and Blood Institute (NHLBI)

Source 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.

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.

Overall Status Completed
Start Date October 2004
Completion Date December 2008
Primary Completion Date December 2008
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Time to Vaso-occlusive Pain Crisis (VOC) Resolution within 30 days
Secondary Outcome
Measure Time Frame
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
Enrollment 150
Condition
Intervention

Intervention Type: Drug

Intervention Name: Nitric Oxide

Description: 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.

Arm Group Label: Inhaled Nitric Oxide

Other Name: INOmax

Intervention Type: Drug

Intervention Name: Placebo

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

Arm Group Label: Placebo

Eligibility

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.

Gender: All

Minimum Age: 10 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
James Baldassarre, MD Study Director Mallinckrodt
Location
Facility:
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, 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
Location Countries

United States

Verification Date

October 2017

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Inhaled Nitric Oxide

Type: Experimental

Description: Participants receive Inhaled nitric oxide (INO)

Label: Placebo

Type: Placebo Comparator

Description: Participants receive Nitrogen gas

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Triple (Participant, Care Provider, Investigator)

Source: ClinicalTrials.gov