Clinical trial NCT00979121
Conditions: Sepsis Acute Lung Injury
Keywords: ALI Sepsis statin
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Start date: 2010-01-01; Completion date: 2013-11-01
Enrollment: 745 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Objective: assess the efficacy and safety of oral rosuvastatin in patients with sepsis-induced Acute Lung Injury (ALI).

Hypothesis: Rosuvastatin therapy will improve mortality in patients with sepsis-induced ALI.

Detailed description:
Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) involves extensive inflammation in the lungs that can lead to rapid respiratory failure. These conditions are most commonly caused by pneumonia, generalized infection, or severe trauma to the lungs, but can also be less commonly caused by smoke or salt water inhalation, drug overdose, or shock.

For some people, ALI/ARDS resolves without treatment, but many severe cases result in hospitalization in the intensive care unit (ICU), where 30% to 40% of cases end in mortality. Current treatments for ALI/ARDS include assisted breathing with a ventilator, supportive care, and management of the underlying causes.

Upon admission to the ICU, Rosuvastatin or placebo was administered through an enteral feeding tube or administered orally following extubation when patients were able to safely take oral medications. The type and placement of the enteral feeding tube (nasogastric, nasoenteric, PEG, orogastric, oroenteric, etc.) and the ability to safely take oral medications was determined by the patient's primary team. Study drug was blinded with an identical appearing placebo. The first study drug dose (rosuvastatin or placebo) was administered within 4 hours of randomization as a loading dose of 40 mg.

Blood pressure, heart rate, ventilation settings, and various blood factors were measured during treatment. Phone-based follow-up assessments occurred at months 6 and 12 after ICU discharge and included measurements of health-related quality of life; psychological, neurocognitive, and physical activity outcomes; healthcare utilization; and mortality.

Arms: arm 1: Half of the subjects were randomized to the active drug (Rosuvastatin).

Dosage, Form, and Frequency: drug was provided as 10mg tablets and administered through an enteral feeding tube or orally (following extubation when patients were able to safely take oral medications). An initial 40mg loading dose was administered followed by a daily 20 mg maintenance dose. Maintenance dosing was adjusted for renal failure not compensated by renal replacement therapy.

Duration: drug was administered daily until:

1. 28 days after randomization or 3 days after ICU discharge (whichever comes first),
2. Discharge from study hospital,
3. Death arm 2: Half of the subjects were randomized to placebo.

10mg tablets identical to active drug were administered through an enteral feeding tube or orally (following extubation when patients were able to safely take oral medications). Dosage, frequency, and duration was provided in the same manner as the active drug.
Interventions: intervention 1: Rosuvastatin intervention 2: Placebo
Intervention descriptions: intervention 1: Subjects received an initial 40mg loading dose followed by 20 mg of study drug daily by mouth or feeding tube for 28 days or until discharged from the study hospital. intervention 2: Subjects received placebo by mouth or feeding tube daily for 28 days or until discharged from study hospital.

Protocol documents: