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Effect of Inhaled Nitric Oxide in Acute Chest Syndrome (INOSTA Study)

This study is currently recruiting participants.
Verified November 2012 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Collaborator:
INO Therapeutics
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00748423
First received: September 5, 2008
Last updated: December 18, 2012
Last verified: November 2012
History of Changes
  Purpose

Acute chest syndrome (ACS) is a frequent and potentially life-threatening pulmonary illness. It is a complication of sickle cell disease and is the leading cause of death from this disease in adults. Several pathologic processes are recognized causes of ACS, including infectious diseases, hypoventilation secondary to chest pain, in situ thrombosis and pulmonary fat embolism. Inhaled nitric oxide (iNO) has been shown to be a pulmonary vasodilatator with minimal systemic effects and has also been shown to improve gas exchange in both animal and human acute lung injury (ALI).

The combined effects of iNO gas of improving pulmonary ventilation to perfusion matching, reducing alveolar and systemic inflammation, modulate the course of acute chest syndrome, which combine the physiopathology of vaso-occlusive crisis and acute lung injury.

We hypothesise inhaled NO will improve oxygenation and clinical outcome of sickle cell disease patients with acute chest syndrome.


Condition Intervention Phase
Sickle Cell Disease
Acute Chest Syndrome
 Drug: Nitric Oxide
Drug: Placebo
 Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Bicentric Study of the Effect of Inhaled Nitric Oxide Compared to Placebo in Acute Chest Syndrome of Adult Sickle Cell Patients

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Percentage of patients with treatment failure [ Time Frame: at day 3 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Proportion of hypoxemic patients defined by a PaO2/FiO2 ratio < 300 [ Time Frame: at day 3 ] [ Designated as safety issue: Yes ]
  • Variation of pulmonary arterial systolic pressure evaluated by echocardiography [ Time Frame: at day 1, day 3 and end of study ] [ Designated as safety issue: Yes ]
  • Length of hospitalisation [ Time Frame: from day 0 to day 15 (max) ] [ Designated as safety issue: Yes ]
  • Pain assessment and the cumulative dose of parenteral opioids per body weight [ Time Frame: during the first three days and during entire hospitalization ] [ Designated as safety issue: Yes ]
  • Proportion of patients requiring transfusion therapy (simple or exchange) [ Time Frame: from day 1 to end of study ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 260
Study Start Date: December 2008
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Nitric Oxide in nitrogen
 Drug: Nitric Oxide
NO in inhalation for 3 days
Other Name: Nitric Oxide
Placebo Comparator: 2
Nitrogen
 Drug: Placebo
Placebo in inhalation for 3 days
Other Name: "Nitrogen" placebo

Detailed Description:

Objectives: To compare the outcome and duration of acute chest syndrome (ACS) in patients with sickle cell disease (SCD) treated with iNO to that of similar episodes experienced by patients which receive a placebo.

Study design: Bi-center, prospective, randomized, controlled clinical trial

  • Enrollment: 24 months
  • Patients will be treated for 72 hours
  • Patients will be followed for 15 days or until discharged home

Sample size:

  • The study will accrue a maximum of 240 patients
  • Progress of the trial will be reviewed by an independent data and safety monitoring committee to determine if randomization should stop for safety reasons.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with sickle cell disease (Hemoglobin genotypes characterized by standard procedures as homozygous hemoglobin SS, hemoglobin SC, and S beta thalassemia)
  • Diagnosis of acute chest syndrome based on the presence of fever, dyspnea or chest pain, associated with new pulmonary infiltrates on chest X-ray

Exclusion Criteria:

  • Patient has been hospitalised < 14 days ago
  • Patients presenting with clinically diagnosed bacterial infections
  • Patients who have received an exchange transfusion in the last 30 days or are in a transfusion program.
  • Current pregnancy or lactation
  • Patient who is currently enrolled in any other investigational drug study
  • Previous participation in this study

  • Any of the following medical conditions:

    • Immediate need of ventilatory support wih orotracheal intubation
    • Hemodynamic instability
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00748423

Contacts
Contact: MAITRE Bernard, MD, PHD (0) 1 49 81 23 78 ext +33 bernard.maitre@hmn.aphp.fr
Contact: Rarison Onja (0) 1 49 81 33 87 ext +33 onja.rarison@hmn.aphp.fr

Locations
France
Réanimation Médicale, Hôpital A Chenevier-H Mondor Recruiting
Creteil, France, 94 000
Contact: MAITRE Bernard     (0) 1 49 81 23 78 ext +33     bernard.maitre@hmn.aphp.fr    
Contact: FARTOUKH Murielle, MD     (0) 1 56 01 65 36 ext +33     muriel.fartoukh@tnn.aphp.fr    
Principal Investigator: MAITRE Bernard, MD, PHD            
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
INO Therapeutics
Investigators
Principal Investigator: MAITRE Bernard, MD, PHD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00748423     History of Changes
Other Study ID Numbers: P060701
Study First Received: September 5, 2008
Last Updated: December 18, 2012
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Inhaled drug
Acute lung injury
Nitric oxide
Sickle cell

Additional relevant MeSH terms:
Anemia, Sickle Cell
Acute Chest Syndrome
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
 Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Cardiovascular Agents
Protective Agents

ClinicalTrials.gov processed this record on May 19, 2013