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Inhaled Nitric Oxide for Pediatric Painful Sickle Crisis

This study has been terminated.
(18 or 20 enrolled, stopped due to paucity of available participants)
Sponsor:
Collaborator:
FDA Office of Orphan Products Development
Information provided by (Responsible Party):
Debra Weiner, Boston Children's Hospital
ClinicalTrials.gov Identifier:
NCT00142051
First received: August 31, 2005
Last updated: July 15, 2017
Last verified: July 2014
  Purpose
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 Drug: oxygen Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: Inhaled Nitric Oxide for Pediatric Painful Sickle Crisis

Resource links provided by NLM:


Further study details as provided by Debra Weiner, Boston Children's Hospital:

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. [ Time Frame: every 4 hrs x duration of hospitalization ]

Secondary Outcome Measures:
  • Secondary outcome measures to evaluate efficacy [ Time Frame: Duration of hospitalization, followup ]
  • Longitudinal analyses of change in VAS pain score over 16 hours. [ Time Frame: every 4 hrs, duration of hospitalization ]
  • Change in pain score using a 5 point descriptive scale and a 5 point relief scale. [ Time Frame: 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. [ Time Frame: every 4 hrs, duration of hospitalization ]
  • Use of pain medication: cumulative dose of parenteral narcotic pain medications. [ Time Frame: While patient on parenteral narcotic ]
  • Duration of hospitalization. [ Time Frame: Time of discharge ]
  • Inflammatory markers/mediators. [ Time Frame: 0, 16 and q 24 hrs during hospitalization ]
  • Secondary outcome measures to evaluate safety are: [ Time Frame: 4, 8, 16, 24 hrs methb, constant NO2, 02 during inhalation ]
  • Maximum concentration of methemoglobin. [ Time Frame: 0, 4, 8, 16, 24 hrs ]
  • Maximum concentration of nitrogen dioxide (NO2) delivered. [ Time Frame: continuous over 24 hrs of inhalaiton ]
  • 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 ]
  • Maximum and minimum vital signs: pulse, respiratory rate, blood pressure. [ Time Frame: every 4 hrs during hospitalization ]

Enrollment: 18
Study Start Date: April 2005
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
inhaled NO
Drug: nitric oxide
80 ppm 8 hrs, 40 ppm 8 hrs, 20 ppm 4 hrs, 10 ppm 4 hrs
Placebo Comparator: 2
room air inhalation
Drug: oxygen
oxygen fi02 21% (room air)

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.
  Eligibility

Ages Eligible for Study:   9 Years to 22 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00142051

Locations
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Boston Children’s Hospital
FDA Office of Orphan Products Development
Investigators
Principal Investigator: Debra Weiner, MD, PhD Boston Children’s Hospital
  More Information

Publications:
Responsible Party: Debra Weiner, Assistant Professor of Pediatrics, Harvard Medical School, Boston Children's Hospital
ClinicalTrials.gov Identifier: NCT00142051     History of Changes
Other Study ID Numbers: 04-09-119
FD-R-002560-01 ( Other Grant/Funding Number: FDA )
Study First Received: August 31, 2005
Last Updated: July 15, 2017

Keywords provided by Debra Weiner, Boston Children's Hospital:
sickle cell disease
pain crisis
vaso-occlusive crisis
nitric oxide

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Gasotransmitters
Protective Agents

ClinicalTrials.gov processed this record on July 24, 2017