Activated Protein C to Treat Acute Lung Injuries

• Status: Terminated
• Trial end date: 2007-02-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to test the efficacy of activated Protein C (Xigris) for improving clinical outcomes in individuals with acute lung injury (ALI).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Francisco
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Drotrecogin alfa activated; Protein C

Criteria

Inclusion Criteria:

• PaO2/FiO2 levels less than or equal to 300

• Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph

• Positive pressure ventilation through an endotracheal tube or tracheostomy

• No clinical evidence of left atrial hypertension that would explain the pulmonary infiltrates; if measured, pulmonary arterial wedge pressure less than or equal to 18 mm Hg

Exclusion Criteria:

• Family / patient refuses

• Patient / surrogate unavailable

• Attending refuses

• Age younger than 18 years

• Severe sepsis and Acute Physiology and Chronic Health Evaluation (APACHE) II scores greater than 25 within 48 hours of onset of severe sepsis

• Greater than 72 hours since all inclusion criteria are met

• Neuromuscular disease that impairs ability to ventilate without assistance, such as C5 or higher spinal cord injury, amyotrophic lateral sclerosis, Guillain-Barré syndrome, myasthenia gravis, or kyphoscoliosis

• Pregnant

• Severe chronic respiratory disease

• Weighs more than 160 kg

• Burns to more than 70% of total body surface area

• Cancer or other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%

• Bone marrow transplant in the 5 years prior to study entry

• Not committed to full support

• Severe chronic liver disease, as determined by a Child-Pugh Score of 11 to 15

• Diffuse alveolar hemorrhage from vasculitis

• Participation in another experimental medication study within 30 days of study entry

• Patients who have already received APC therapy

• Active internal bleeding

• Hemorrhagic or ischemic stroke within 3 months of study entry

• Intracranial or intraspinal surgery or severe head trauma within 2 months of study entry

• Trauma with an increased risk of life-threatening bleeding

• Presence of an epidural catheter

• Intracranial neoplasm mass lesion or evidence of cerebral herniation

• High risk of intracranial hemorrhage, as determined by 1 of the following: 1) intracranial or spinal pathology which places individuals at risk for intracranial hemorrhage (e.g., arterio-venous malformation or previous intracranial bleeding events, not including meningitis); 2) acute change in neurological status with focal neurological findings; 3) documented intracranial hypertension by lumbar puncture or imaging; or 4) seizures in which there is a clinical suspicion of intracranial hemorrhage

• Known bleeding diathesis

• Concurrent therapeutic heparin (greater than 14 units/kg/hr)

• Platelet count less than 30,000 x 106/L, even if the platelet count is increased after transfusions

• Prothrombin time greater than 3.0 INR

• Gastrointestinal bleeding within 6 weeks of study entry

• Concurrent need for systemic anticoagulation with therapeutic unfractionated heparin or low molecular weight heparin during the study drug infusion

• Concurrent administration of an anticoagulant (other than subcutaneous heparin for prophylaxis)

• Concurrent need for platelet glycoprotein Iib/IIIa antagonists or any other antiplatelet agents (patients taking aspirin or other antiplatelet agents at study entry are eligible if medication can be discontinued during study drug infusion)

• Surgery within 30 days of study entry and single organ failure