Acute lung injury Respiratory Lung injury
Conditions
Interventions
Patients will be randomised to palifermin 60 µg/kg or normal saline placebo daily as a bolus intravenous injection for up to 6 days. Administration will not occur through an intravenous line that has
Sponsors
Belfast Health and Social Care Trust (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 23/01/2014: 1. Aged greater than 18 years, either sex 2. Acute lung injury (ALI) as defined by acute onset of: 2.1. Hypoxic respiratory failure (partial pressure of oxygen in arterial blood [PaO2]/fraction of inspired oxygen [FiO2] less than or equal to 40 kPa) 2.2. Bilateral infiltrates on chest X-ray consistent with pulmonary oedema 2.3. No clinical evidence of left atrial hypertension or if measured, a pulmonary arterial occlusion pressure (PAOP) less than or equal to 18 mmHg 2.4. Requirement for positive pressure mechanical ventilation via an endotracheal tube or tracheostomy All ALI criteria above must occur within the same 24-hour period. The onset of ALI is when the last ALI criterion is met. Patients must be enrolled within 72 hours of ALI onset. Previous inclusion criteria: 1. Aged greater than 18 years, either sex 2. Acute lung injury (ALI) as defined by acute onset of: 2.1. Hypoxic respiratory failure (partial pressure of oxygen in arterial blood [PaO2]/fraction of inspired oxygen [FiO2] less than or equal to 40 kPa) 2.2. Bilateral infiltrates on chest X-ray consistent with pulmonary oedema 2.3. No clinical evidence of left atrial hypertension or if measured, a pulmonary arterial occlusion pressure (PAOP) less than or equal to 18 mmHg 2.4. Requirement for positive pressure mechanical ventilation via an endotracheal tube or tracheostomy All ALI criteria above must occur within the same 24-hour period. The onset of ALI is when the last ALI criterion is met. Patients must be enrolled within 48 hours of ALI onset.
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 23/01/2014: 1. Aged less than 18 years 2. More than 48 hours from the onset of ALI 3. Pregnancy 4. Participation in a clinical trial of an investigational medicinal product within 30 days 5. Consent declined 6. Current treatment with KGF 7. Known hypersensitivity to palifermin or Escherichia coli derived proteins 8. Previous adverse reaction to palifermin 9. Active history of malignancy excluding haematological malignancies 10. Chronic liver disease with Child-Pugh score greater than 12 Previous exclusion criteria: 1. Aged less than 18 years 2. More than 48 hours from the onset of ALI 3. Pregnancy 4. Participation in a clinical trial of an investigational medicinal product within 30 days 5. Consent declined 6. Current treatment with KGF 7. Patients with pancreatitis 8. Known hypersensitivity to palifermin or Escherichia coli derived proteins 9. Previous adverse reaction to palifermin 10. History of active malignancy 11. Chronic liver disease with Child-Pugh score greater than 12
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Oxygenation index (OI) at day 7 or the last available OI prior to patient discontinuation from the study. OI is a physiological index of the severity of ALI and measures both impaired oxygenation and the amount of mechanical ventilation delivered. We and others have shown OI is independently predictive of mortality in patients with ALI. We have chosen day 7 as we expect this time interval will minimise the competing effects of death and extubation, while allowing a sufficient time interval for a biological effect to occur. OI is calculated as (mean airway pressure [cm H20] x FiO2 x 100) = PaO2 (kPa). These simple measurements are easily and routinely collected as part of standard ventilator practice. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Oxygenation index (OI) at days 3 and 14 2. Physiological indices of acute lung injury, as measured by respiratory compliance (Crs), P/F ratio, and the pulmonary dead space fraction at days 3, 7 and 14 3. Change in sequential organ failure assessment (SOFA) score from baseline to day 7 and 14 4. Safety and tolerability as assessed by the occurrence of AEs and Suspected Unexpected Serious Reactions (SUSARs) Although the duration of ventilation and ICU stay as well as ICU and hospital mortality and 28-day mortality will also be documented, these important clinical outcomes are not included as major outcome measures as the study is not adequately powered to assess these outcomes. | — |
Countries
United Kingdom
Outcome results
None listed