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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Bicentric Study of the Effect of Inhaled Nitric Oxide Compared to Placebo in Acute Chest Syndrome of Adult Sickle Cell Patients

Conditions
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Sickle Cell Disease, Acute Chest Syndrome

Intervention / Treatment
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* Drug: Nitric Oxide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Nitric Oxide in nitrogen | Drug: Nitric Oxide<br>* NO in inhalation for 3 days<br>|
| Placebo Comparator: 2<br>Nitrogen | Drug: Placebo<br>* Placebo in inhalation for 3 days<br>* Other names: Nitrogen placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with treatment failure |  | at day 3 | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inhaled drug, Acute lung injury, Nitric oxide, Sickle cell