Clinical trial NCT00748423: Effect of Inhaled Nitric Oxide in Acute Chest Syndrome (INOSTA Study)
Official title: Bicentric Study of the Effect of Inhaled Nitric Oxide Compared to Placebo in Acute Chest Syndrome of Adult Sickle Cell Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Sickle Cell Disease
Acute Chest Syndrome
Keywords: Inhaled drug
Acute lung injury
Nitric oxide
Sickle cell
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Mallinckrodt
First posted: 2008-09-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Percentage of patients with treatment failure
timeFrame: at day 3
Secondary outcomes:
measure: Proportion of hypoxemic patients defined by a PaO2/FiO2 ratio < 300
timeFrame: at day 3
measure: Variation of pulmonary arterial systolic pressure evaluated by echocardiography
timeFrame: at day 1, day 3 and end of study
measure: Length of hospitalisation
timeFrame: from day 0 to day 15 (max)
measure: Pain assessment and the cumulative dose of parenteral opioids per body weight
timeFrame: during the first three days and during entire hospitalization
measure: Proportion of patients requiring transfusion therapy (simple or exchange)
timeFrame: from day 1 to end of study
Other outcomes:
Locations:
city: Creteil
country: France
facility: Réanimation Médicale, Hôpital A Chenevier-H Mondor
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: MAITRE Bernard, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Maitre B, Djibre M, Katsahian S, Habibi A, Stankovic Stojanovic K, Khellaf M, Bourgeon I, Lionnet F, Charles-Nelson A, Brochard L, Lemaire F, Galacteros F, Brun-Buisson C, Fartoukh M, Mekontso Dessap A. Inhaled nitric oxide for acute chest syndrome in adult sickle cell patients: a randomized controlled study. Intensive Care Med. 2015 Dec;41(12):2121-9. doi: 10.1007/s00134-015-4060-2. Epub 2015 Oct 2.