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

Sickle Cell Disease Clinical Trial

— INOSTA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00748423
• Other study ID #: P060701
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: September 5, 2008
• Last updated: August 1, 2013
• Start date: December 2008
• Est. completion date: December 2012

Study information

• Verified date: July 2013
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Chest Syndrome
• Anemia, Sickle Cell
• Sickle Cell Disease
• Syndrome

Intervention

Drug:
• Nitric Oxide
NO in inhalation for 3 days
• Placebo
Placebo in inhalation for 3 days

Locations

Country	Name	City	State
France	Réanimation Médicale, Hôpital A Chenevier-H Mondor	Creteil

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	INO Therapeutics

Country where clinical trial is conducted

France, 

Outcome

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