Effect of Atorvastatin on the Frequency of Ventilator-associated Pneumonia in Patients With Ischemic Stroke

Ventilator-associated pneumonia (VAP) is an important cause of morbidity and mortality in ventilated critically ill patients specially in intensive care unit (ICU). It is associated with an increased duration of mechanical ventilation, high death rates and increased healthcare costs in China. However, VAP is preventable and many practices have been demonstrated to reduce the incidence of this disease, but the morbidity is still so high. So much more methods of prevention should be needed to reduce the incidence of VAP.

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) present anti-inflammatory and immunomodulatory effects besides their ability to regulate cholesterol composition. So it is hypothesized that early use of statin may prevent some of the infection disease such as VAP.

Actually, Two studies have showed that statin treatment is associated with reduced risk of pneumonia. However, the relationship between statins and reduced risk of pneumonia is not consistent.

After reviewing some of the guidelines,meta analyses and system reviews, the investigator find that advanced age,immune suppression from disease or medication and specially depressed level of consciousness are the risk factors of VAP. So the investigator assumes that early use of statin may give us a favorable outcome in the patients with coma or in the patients with severe disease (Acute Physiology and Chronic Health Evaluation II score > 15 or Glasgow coma score < 7).

In addition there is no prospective study to investigate the role of statins in VAP in the patients with ischemic stroke. The investigator hopes that this study can approve the relationship between statins and reduced risk of VAP in the patients with ischemic stroke. And it can improve the processes,outcomes and costs of critical care as well.

Study Overview

• Status: Unknown
• Conditions: Ischemic Stroke; Ventilator-associated Pneumonia
• Intervention / Treatment: Drug: Atorvastatin; Drug: Placebo

Detailed Description

This is a one-center, two-arm, randomized, single-blinded, controlled trial. When a patient with ischemic stroke who needs mechanic ventilation is admitted to ICU,a sealed envelop will be opened which decide whether the patient is assigned to the placebo arm or the atorvastatin arm. During they stay in ICU, one tablet of atorvastatin (40mg) or one tablet of placebo will be administered. Atorvastatin or placebo will be administered through an enteral feeding tube or administered orally when patients are able to safely take oral medications.

VAP diagnosis accords with the comprehensive evidence-based clinical practice guidelines for ventilator-associated pneumonia:Diagnosis and treatment which was published in 2008.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Liu ChunYan, MD; Phone Number: 021-64923400; Email: doctorlcy@sina.com
• Study Contact Backup: Name: Yu YueTian, MD; Phone Number: 021-64923400; Email: fishyyt@sina.com

Study Locations

• China
  • Shanghai, China, 201199
    • Recruiting
    • Shanghai Minhang Central Hospital
    • Contact: Liu Chunyan, MD; Phone Number: 862164923400; Email: doctorlcy@sina.com
    • Contact: Yu Yuetian, MD; Phone Number: 862164923400; Email: fishyyt@sina.com
    • Principal Investigator: Liu Chunyan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All consecutive patients with ischemic stroke who are admitted to Intensive Care Unit(ICU) between 1st March.2012 at 00:00 hours (midnight) and the finish date of 31st March. 2014 at 23:59 hours (11.59 pm). Patients who are already in the ICU prior to 1st March. 2012 at 00:00 hours will not be included in the study.
• Duration of mechanical ventilation > 48h through tracheal tube or tracheotomy
• Informed consent

Exclusion Criteria:

• Patients with pneumonia when they are admitted to ICU.
• Previous use of statin for cholesterol regulation.
• Chronic liver disease or active liver disease.
• Increase of CPK (over 3 times the upper limit) during hospitalization.
• Malnutrition.
• Pregnancy.
• Unwilling to continue the therapy during hospitalization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atorvastatin(50 characters)	Drug: Atorvastatin; Patients will receive 40mg atorvastatin(one tablet) over night via enteral feeding tube or per os during they stay in ICU at most thirty days.; Other Names: Lipitor
Placebo Comparator: Placebo(50 characters)	Drug: Placebo; The smell and shape of placebo are the same as atorvastatin; Other Names: No other name

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cumulative frequency of ventilator-associated pneumonia	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality		30 days
Ventilation free days		30 days
Antibiotic free days		30 days
Whether the bacteria of multidrug-resistance can be isolated from the sputum culture	We will find whether methicillin-resistant Staphylococcus aureus(MRSA), extended-spectrum beta-lactamase(ESBLs) or Vancomycin-resistant enterococcus (VRE)can be isolated from the sputum culture.	30 days
Adverse effects	Creatine kinase of more than three times the upper normal limit or hepatic enzyme dysfunction.	30 days

Collaborators and Investigators

• Sponsor: Shanghai Minhang Central Hospital
• Collaborators: Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: Liu ChunYan, MD, Shanghai Minhang Central Hospital

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Anticipated): February 1, 2014
• Study Completion (Anticipated): February 1, 2014

Study Registration Dates

• First Submitted: March 2, 2012
• First Submitted That Met QC Criteria: March 9, 2012
• First Posted (Estimate): March 12, 2012

Study Record Updates

• Last Update Posted (Estimate): February 26, 2013
• Last Update Submitted That Met QC Criteria: February 24, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: Morbidity; Mortality; Atorvastatin; Ventilator-associated pneumonia; Ischemic stroke
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Cross Infection; Iatrogenic Disease; Brain Ischemia; Infarction; Brain Infarction; Healthcare-Associated Pneumonia; Stroke; Ischemic Stroke; Ischemia; Pneumonia; Cerebral Infarction; Pneumonia, Ventilator-Associated; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: MHC Hospital 01