Inhaled Nitric Oxide for Pediatric Painful Sickle Crisis

NCT00142051 | Terminated Phase 2 DMC

• 2 other identifiers: 04-09-119FD-R-002560-01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Disease

Keywords

sickle cell disease; pain crisis; vaso-occlusive crisis; nitric oxide

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• Secondary outcome measures to evaluate efficacy

  Duration of hospitalization, followup

• 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

Study Arms (2)

1

EXPERIMENTAL

inhaled NO

Drug: nitric oxide

2

PLACEBO COMPARATOR

room air inhalation

Drug: oxygen

Interventions

nitric oxide DRUG

80 ppm 8 hrs, 40 ppm 8 hrs, 20 ppm 4 hrs, 10 ppm 4 hrs

1

oxygen DRUG

oxygen fi02 21% (room air)

2

Eligibility Criteria

• Age: 9 Years - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• \> 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

Sponsors & Collaborators

• Boston Children's Hospital: lead
• FDA Office of Orphan Products Development: collaborator

Study Sites (1)

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Related Publications (2)

• 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.

  PMID: 21364138 BACKGROUND

• 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.

  PMID: 12622584 BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell; Vaso-Occlusive Crises

Interventions

Nitric Oxide; Oxygen

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Reactive Nitrogen Species; Free Radicals; Inorganic Chemicals; Nitrogen Oxides; Nitrogen Compounds; Oxides; Oxygen Compounds; Organic Chemicals; Chalcogens; Elements; Gases

Study Officials

• Debra Weiner, MD, PhD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics, Harvard Medical School

Study Record Dates

• First Submitted: August 31, 2005
• First Posted: September 2, 2005
• Study Start: April 1, 2005
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: February 23, 2023

Record last verified: 2023-02

Locations

US (1)