Sickle Cell Disease
Conditions
Keywords
sickle cell disease, pain crisis, vaso-occlusive crisis, nitric oxide
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.
Interventions
DRUGnitric oxide
80 ppm 8 hrs, 40 ppm 8 hrs, 20 ppm 4 hrs, 10 ppm 4 hrs
DRUGoxygen
oxygen fi02 21% (room air)
Sponsors
FDA Office of Orphan Products Development
Boston Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
9 Years to 22 Years
Healthy volunteers
No
Inclusion criteria
1. Hemoglobin SS, Hemoglobin Sß0thal or Hemoglobin SC documented by prior hemoglobin electrophoresis. 2. 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. 3. Acute pain crisis defined as pain in abdomen, back and/or extremities that cannot be explained by a diagnosis other than sickle cell disease. 4. 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
1. \> 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. 2. Pain crisis treated at a medical facility within the last 12 hours. 3. Use of investigational drugs other than hydroxyurea within the last 30 days. 4. Significant respiratory compromise (initial SaO2 \< 90%) and/or patients likely to have acute chest syndrome (chest pain and infiltrate) will be eliminated. 5. Clinically significant acute or chronic cardiac dysfunction. 6. Acute priapism. 7. New focal neurologic symptoms. 8. Concurrent documented or suspected bacterial or parvovirus infection. 9. Temperature \> 38.4ºC. These patients may have concomitant infection. 10. Transfusion within 30 days or chronic transfusion therapy. 11. Pregnant female 12. Cigarette smoker \> 1/2 ppd. 13. Allergy to morphine \-
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Difference in change in mean pain score (visual analog scale) after 16 hours of treatment between patients treated with INO and placebo. | every 4 hrs x duration of hospitalization |
Secondary
| Measure | Time frame |
|---|---|
| Longitudinal analyses of change in VAS pain score over 16 hours. | every 4 hrs, duration of hospitalization |
| Change in pain score using a 5 point descriptive scale and a 5 point relief scale. | every 4 hours duration of hospitalization |
| Time to pain score less than 5 cm for 2 consecutive VAS pain assessments 4 hours apart and not using parenteral narcotics. | every 4 hrs, duration of hospitalization |
| Use of pain medication: cumulative dose of parenteral narcotic pain medications. | While patient on parenteral narcotic |
| Duration of hospitalization. | Time of discharge |
| Secondary outcome measures to evaluate efficacy | Duration of hospitalization, followup |
| Secondary outcome measures to evaluate safety are: | 4, 8, 16, 24 hrs methb, constant NO2, 02 during inhalation |
| Maximum concentration of methemoglobin. | 0, 4, 8, 16, 24 hrs |
| Maximum concentration of nitrogen dioxide (NO2) delivered. | continuous over 24 hrs of inhalaiton |
| Minimum percent oxygen saturation of hemoglobin (by pulse oximetry). | continuous over 24 hrs of inhalation then every 4 hrs for duration of hospitalization |
| Maximum and minimum vital signs: pulse, respiratory rate, blood pressure. | every 4 hrs during hospitalization |
| Inflammatory markers/mediators. | 0, 16 and q 24 hrs during hospitalization |
Countries
United States
Outcome results
None listed