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.

Condition	Intervention	Phase
Sickle Cell Disease	Drug: Nitric Oxide	Phase II

Further Study Details: 

Primary Outcomes: Difference in change in mean pain score (visual analog scale) after 16 hours of treatment between patients treated with INO and placebo.
Secondary Outcomes: Secondary outcome measures to evaluate efficacy; a. Longitudinal analyses of change in VAS pain score over 16 hours.; b. Change in pain score using a 5 point descriptive scale and a 5 point relief scale.; c. Time to pain score 4 cm or less for 2 consecutive VAS pain assessments 4 hours apart and not using parenteral narcotics.; d. Use of pain medication: cumulative dose of parenteral narcotic pain medications.; e. Duration of hospitalization.; f. Inflammatory markers/mediators.; Secondary outcome measures to evaluate safety are:; a. Maximum concentration of methemoglobin.; b. Maximum concentration of nitrogen dioxide (NO2) delivered.; c. Minimum percent oxygen saturation of hemoglobin (SpO2 by pulse oximetry).; d. Maximum and minimum vital signs: pulse, respiratory rate, blood pressure.
Expected Total Enrollment:  20

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.

Ages Eligible for Study:  10 Years   -   21 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

1. HbSS, HbSß0thal or HbSC documented by prior hemoglobin electrophoresis.
2. Age 10 years or greater, age 18 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

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Please refer to this study by ClinicalTrials.gov identifier  NCT00142051

Debra Weiner, MD, PhD      617-355-6624    debra.weiner@childrens.harvard.edu
Pamela Boardman, MPH      617-355-2901    pamela.boardman@childrens.harvard.edu

Massachusetts
      Children''''s Hospital Boston, Boston,  Massachusetts,  02115,  United States; Recruiting

Study chairs or principal investigators

Debra Weiner, MD, PhD,  Principal Investigator,  Children''''s Hospital Boston   

Study ID Numbers:  04-09-119; FD-R-002560-01
Last Updated:  September 1, 2005
Record first received:  August 31, 2005
ClinicalTrials.gov Identifier:  NCT00142051
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-09-06