Inhaled Nitric Oxide for Pediatric Painful Sickle Crisis

Boston Children's Hospital

Status and phase: Terminated; Phase 2

Conditions: Sickle Cell Disease

Treatments: Drug: oxygen; Drug: nitric oxide

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT00142051

04-09-119

FD-R-002560-01 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 18 patients

Sex: All

Ages: 9 to 22 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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18 participants in 2 patient groups, including a placebo group

1

Experimental group

Description:

inhaled NO

Treatment:

Drug: nitric oxide

2

Placebo Comparator group

Description:

room air inhalation

Treatment:

Drug: oxygen