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LiquiVent Product Fact Sheet
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LiquiVent is an oxygen-carrying liquid drug (perflubron) being developed by Alliance Pharmaceutical Corp. for treatment of acute lung injury and acute respiratory distress syndrome. The goal of "liquid ventilation" therapy is to open up collapsed alveoli (air sacs) and facilitate the exchange of respiratory gases while protecting the lungs from the harmful effects of conventional mechanical ventilation.
LiquiVent is being evaluated in a Phase 2-3 clinical (human) study in the United States, Canada and Europe. In addition to this study, LiquiVent has been administered to approximately 300 adult, pediatric, and infant patients in several clinical trials. LiquiVent is being developed and reviewed under U.S. Food and Drug Administration (FDA) "fast track" regulations.
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ACUTE LUNG INJURY
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Acute lung injury (ALI) is a life-threatening condition that can result from a variety of underlying causes. Patients with ALI and acute respiratory distress (ARDS; the most severe stage of ALI) experience disruption of the membranes of the alveoli, causing leakage of fluids and inflammatory cells into the lungs. This is associated with atelectasis (collapse of alveoli), shunting (re-routing) of blood around lung tissues, decreased compliance (increased stiffening) of the lungs, and inadequate gas exchange. |
CONVENTIONAL MECHANICAL VENTILATION
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As the lungs become less able to provide oxygen to, and remove carbon dioxide from, the blood, acidosis and oxygen starvation threaten all organs. Standard therapy for ALI involves forcibly opening the alveoli by means of positive pressure ventilation and a gas ventilator. This treatment often requires dangerously high oxygen concentrations and gas pressures, which can lead to lung tissue damage by over-inflating the alveoli. ALI patients generally require extended hospitalization in costly intensive care units, and mortality rates are typically 40-50%. 1,2 (1- Critical Care Medicine, 1998, Vol.26, No. 1; 2- The New England Journal of Medicine, 1998, Vol.338, No.6) |
PARTIAL LIQUID VENTILATION
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| The high ventilator pressures needed to expand collapsed, debris-filled alveoli can over-inflate and damage healthy air sacs. By physically holding open the alveoli, LiquiVent may maintain adequate gas exchange and prevent ventilator-induced lung damage. |
Alliance's Partial Liquid VentilationTM technique involves administering LiquiVent to a mechanically ventilated patient by trickling the liquid into the lungs via the endotracheal tube connecting the patient to the ventilator. As the ventilator provides oxygen and removes carbon dioxide, LiquiVent keeps the alveoli open and facilitates the exchange of gases. The pressure settings may then be adjusted to reduce the incidence of ventilator-induced lung injury. LiquiVent is allowed to evaporate and leave the lungs via exhalation when the treatment is completed.
LiquiVent: PROPOSED MECHANISMS OF ACTION
Data from clinical and preclinical studies have indicated that LiquiVent's unique properties may allow it to have multiple potential benefits:
- High solubility for oxygen and carbon dioxide may improve gas exchange and mitigate oxygen toxicity
- High density enables opening of alveoli, which may reduce lung damage due to barotrauma (high ventilatory pressure) and volutrauma (over-extension of alveoli)
- Immiscibility with body fluids and water helps lavage (remove debris from) the lungs
- Low surface tension may allow LiquiVent to act as a surfactant and improve lung compliance (elasticity)
- Positive spreading coefficient allows LiquiVent to be dispersed widely in the lungs to "recruit lung volume" (open collapsed areas) and re-distribute blood flow to the lungs
- Physical barrier effect may hinder formation of debris and leakage of inflammatory cells into the lungs
- Water-like viscosity allows LiquiVent to flow easily into the lungs
- Vapor pressure is ideal for easy removal of LiquiVent from the lungs via exhalation
CLINICAL EXPERIENCE
LiquiVent has been used to treat ALI and ARDS patients with encouraging results.
 A controlled, multicenter Phase 2 study with adult patients demonstrated a significant improvement in "ventilator-free days" and a trend in improved mortality for a subset of patients who received LiquiVent, compared to patients who were treated with conventional mechanical ventilation.
An additional small uncontrolled Phase 2 study with adult ARDS patients, all of whom received LiquiVent treatment, demonstrated a 28-day mortality rate of 6%. A pivotal Phase 2-3 study with adult ALI and ARDS patients is currently being conducted in North America and Europe.
Approximately 800,000 adults in the U.S. receive more than 24 hours of conventional mechanical ventilation each year. Alliance's current clinical studies are focused on addressing the needs of this patient population, and additional studies with pediatric and infant patients are being planned.
More info can be found at: http://www.allp.com/LiquiVent/lv.htm |
