Back to resultsInhaled Nitric Oxide for Pediatric Painful Sickle Crisis
Primary Purpose
Sickle Cell Disease
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
nitric oxide
oxygen
Sponsored by
About this trial
This is an interventional treatment trial for Sickle Cell Disease focused on measuring sickle cell disease, pain crisis, vaso-occlusive crisis, nitric oxide
Eligibility Criteria
Inclusion Criteria: Hemoglobin SS, Hemoglobin Sß0thal or Hemoglobin SC documented by prior hemoglobin electrophoresis. Age 9 years or greater, age 22 years or less; pediatric age range, old enough to comply with mask and give reliable pain assessment score. Acute pain crisis defined as pain in abdomen, back and/or extremities that cannot be explained by a diagnosis other than sickle cell disease. Initial pain score at least 6 cm; to optimize the likelihood of observing a significant difference in change in pain score between INO treated and placebo groups. Based on data from our previous study, it is anticipated that patients will have an average pre-inhalation pain score of approximately 8 cm. Exclusion Criteria: > 24 pain crises in the last 12 months. Patients with very frequent pain crisis may have biologic and/or psychosocial pathophysiology that differs from those with fewer pain crises. Pain crisis treated at a medical facility within the last 12 hours. Use of investigational drugs other than hydroxyurea within the last 30 days. Significant respiratory compromise (initial SaO2 < 90%) and/or patients likely to have acute chest syndrome (chest pain and infiltrate) will be eliminated. Clinically significant acute or chronic cardiac dysfunction. Acute priapism. New focal neurologic symptoms. Concurrent documented or suspected bacterial or parvovirus infection. Temperature > 38.4ºC. These patients may have concomitant infection. Transfusion within 30 days or chronic transfusion therapy. Pregnant female Cigarette smoker > 1/2 ppd. Allergy to morphine -
Sites / Locations
- Children's Hospital Boston
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
1
2
Arm Description
inhaled NO
room air inhalation
Outcomes
Primary Outcome Measures
Difference in change in mean pain score (visual analog scale) after 16 hours of treatment between patients treated with INO and placebo.
Secondary Outcome Measures
Secondary outcome measures to evaluate efficacy
Longitudinal analyses of change in VAS pain score over 16 hours.
Change in pain score using a 5 point descriptive scale and a 5 point relief scale.
Time to pain score less than 5 cm for 2 consecutive VAS pain assessments 4 hours apart and not using parenteral narcotics.
Use of pain medication: cumulative dose of parenteral narcotic pain medications.
Duration of hospitalization.
Inflammatory markers/mediators.
Secondary outcome measures to evaluate safety are:
Maximum concentration of methemoglobin.
Maximum concentration of nitrogen dioxide (NO2) delivered.
Minimum percent oxygen saturation of hemoglobin (by pulse oximetry).
Maximum and minimum vital signs: pulse, respiratory rate, blood pressure.
Full Information
NCT ID
NCT00142051
First Posted
August 31, 2005
Last Updated
February 14, 2023
Sponsor
Boston Children's Hospital
Collaborators
FDA Office of Orphan Products Development
1. Study Identification
Unique Protocol Identification Number
NCT00142051
Brief Title
Inhaled Nitric Oxide for Pediatric Painful Sickle Crisis
Official Title
Inhaled Nitric Oxide for Pediatric Painful Sickle Crisis
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Terminated
Why Stopped
18 or 20 enrolled, stopped due to paucity of available participants
Study Start Date
April 2005 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
August 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Boston Children's Hospital
Collaborators
FDA Office of Orphan Products Development
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Randomized, double blind placebo controlled clinical trial to evaluate effectiveness and safety of inhaled nitric oxide for the treatment of sickle cell painful crisis in pediatric patients with sickle cell disease.
Detailed Description
The specific aim of this study is to evaluate the clinical effectiveness of inhaled nitric oxide (INO) for the treatment of acute vaso-occlusive pain crisis in pediatric patients with sickle cell disease. Nitric oxide (NO) deficiency is known to be central to the pathophysiology of vaso-occlusion. The aim is unchanged from the original application. The study is a randomized, double blind, placebo controlled, clinical trial with eligible patients randomized to receive either NO (with 21% O2 final concentration) for 16 hrs with 8 hr wean (80 ppm 0-8 hrs, 40 ppm 9-16 hrs, 20 ppm 17-20 hrs, 10 ppm 21-24 hrs) or placebo (21% O2 alone) for 24 hrs. The null hypothesis is that there is no difference in change in mean pain score after 16 hours between patients treated with NO and placebo. The primary outcome measure of the study remains the difference in mean change in pain scores between groups as assessed using a 10 cm visual analogue pain scale (VAS). Secondary outcome measures also remain the same. The study is a next step to our completed FDA Orphan Product Development Grant funded study (FD-R-001686) that evaluated safety and efficacy of NO used for 4 hrs for treatment of vaso-occlusive crisis in pediatric patients with sickle cell disease.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
Keywords
sickle cell disease, pain crisis, vaso-occlusive crisis, nitric oxide
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
inhaled NO
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
room air inhalation
Intervention Type
Drug
Intervention Name(s)
nitric oxide
Intervention Description
80 ppm 8 hrs, 40 ppm 8 hrs, 20 ppm 4 hrs, 10 ppm 4 hrs
Intervention Type
Drug
Intervention Name(s)
oxygen
Intervention Description
oxygen fi02 21% (room air)
Primary Outcome Measure Information:
Title
Difference in change in mean pain score (visual analog scale) after 16 hours of treatment between patients treated with INO and placebo.
Time Frame
every 4 hrs x duration of hospitalization
Secondary Outcome Measure Information:
Title
Secondary outcome measures to evaluate efficacy
Time Frame
Duration of hospitalization, followup
Title
Longitudinal analyses of change in VAS pain score over 16 hours.
Time Frame
every 4 hrs, duration of hospitalization
Title
Change in pain score using a 5 point descriptive scale and a 5 point relief scale.
Time Frame
every 4 hours duration of hospitalization
Title
Time to pain score less than 5 cm for 2 consecutive VAS pain assessments 4 hours apart and not using parenteral narcotics.
Time Frame
every 4 hrs, duration of hospitalization
Title
Use of pain medication: cumulative dose of parenteral narcotic pain medications.
Time Frame
While patient on parenteral narcotic
Title
Duration of hospitalization.
Time Frame
Time of discharge
Title
Inflammatory markers/mediators.
Time Frame
0, 16 and q 24 hrs during hospitalization
Title
Secondary outcome measures to evaluate safety are:
Time Frame
4, 8, 16, 24 hrs methb, constant NO2, 02 during inhalation
Title
Maximum concentration of methemoglobin.
Time Frame
0, 4, 8, 16, 24 hrs
Title
Maximum concentration of nitrogen dioxide (NO2) delivered.
Time Frame
continuous over 24 hrs of inhalaiton
Title
Minimum percent oxygen saturation of hemoglobin (by pulse oximetry).
Time Frame
continuous over 24 hrs of inhalation then every 4 hrs for duration of hospitalization
Title
Maximum and minimum vital signs: pulse, respiratory rate, blood pressure.
Time Frame
every 4 hrs during hospitalization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
9 Years
Maximum Age & Unit of Time
22 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Hemoglobin SS, Hemoglobin Sß0thal or Hemoglobin SC documented by prior hemoglobin electrophoresis.
Age 9 years or greater, age 22 years or less; pediatric age range, old enough to comply with mask and give reliable pain assessment score.
Acute pain crisis defined as pain in abdomen, back and/or extremities that cannot be explained by a diagnosis other than sickle cell disease.
Initial pain score at least 6 cm; to optimize the likelihood of observing a significant difference in change in pain score between INO treated and placebo groups. Based on data from our previous study, it is anticipated that patients will have an average pre-inhalation pain score of approximately 8 cm.
Exclusion Criteria:
> 24 pain crises in the last 12 months. Patients with very frequent pain crisis may have biologic and/or psychosocial pathophysiology that differs from those with fewer pain crises.
Pain crisis treated at a medical facility within the last 12 hours.
Use of investigational drugs other than hydroxyurea within the last 30 days.
Significant respiratory compromise (initial SaO2 < 90%) and/or patients likely to have acute chest syndrome (chest pain and infiltrate) will be eliminated.
Clinically significant acute or chronic cardiac dysfunction.
Acute priapism.
New focal neurologic symptoms.
Concurrent documented or suspected bacterial or parvovirus infection.
Temperature > 38.4ºC. These patients may have concomitant infection.
Transfusion within 30 days or chronic transfusion therapy.
Pregnant female
Cigarette smoker > 1/2 ppd.
Allergy to morphine
-
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Debra Weiner, MD, PhD
Organizational Affiliation
Boston Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
21364138
Citation
Gladwin 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.
Results Reference
background
PubMed Identifier
12622584
Citation
Weiner DL, Hibberd PL, Betit P, Cooper AB, Botelho CA, Brugnara C. Preliminary assessment of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease. JAMA. 2003 Mar 5;289(9):1136-42. doi: 10.1001/jama.289.9.1136. Erratum In: JAMA. 2004 Aug 25;292(8):925.
Results Reference
background
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Inhaled Nitric Oxide for Pediatric Painful Sickle Crisis
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