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

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT00748423

Collaborator

Mallinckrodt (Industry)

100

Enrollment

Location

Arms

Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Sickle Cell Disease Acute Chest Syndrome	Drug: Nitric Oxide Drug: Placebo	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, 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

Study Start Date :

Dec 1, 2008

Actual Primary Completion Date :

Dec 1, 2012

Actual Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Nitric Oxide in nitrogen	Drug: Nitric Oxide NO in inhalation for 3 days
Placebo Comparator: 2 Nitrogen	Drug: Placebo Placebo in inhalation for 3 days Other Names: "Nitrogen" placebo

Arm

Intervention/Treatment

Experimental: 1

Nitric Oxide in nitrogen

Drug: Nitric Oxide

NO in inhalation for 3 days

Placebo Comparator: 2

Nitrogen

Drug: Placebo

Placebo in inhalation for 3 days

Other Names:

"Nitrogen" placebo

Outcome Measures

Primary Outcome Measures

Percentage of patients with treatment failure [at day 3]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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