Effect of Statin Therapy on Mortality in Patients With Ventilator Associated Pneumonia

Statins with their powerful anti-inflammatory, immunomodulatory, and antioxidant properties make them candidate members to be used in the management of sepsis and different types of infections including pneumonia.

This study aims to determine whether adjunctive statin therapy decreased day- 28 mortality among ICU patients with ventilator-associated pneumonia (VAP) & number of ventilator-free days (after successful weaning) between day 1 and both day 28.

Study Overview

• Status: Completed
• Conditions: VAP - Ventilator Associated Pneumonia
• Intervention / Treatment: Drug: Simvastatin

Detailed Description

This prospective randomized control-controlled triple blind study was conducted on above 18 years who had received mechanical ventilation in the ICU for at least 2 days.

All included cases were subjected to:

• Demographic data,
• Physiological variables
• Simplified Acute Physiology Score II at admission and radiologic score (Weinberg et al., 1984).
• Antibiotics used, and relevant diagnostic and therapeutic interventions in the ICU.
• The Sequential Organ Failure Assessment (SOFA) score and Clinical Pulmonary Infection Score (CPIS) were calculated on the day of enrolment (day 1) and then on days 3, 7, and 14. Patients were monitored daily for evidence of infection.
• The duration of mechanical ventilation, length of ICU stay, and length of hospital stay were recorded.
• The occurrence of myocardial ischemia or infarction was assessed until day 28. Serum levels of creatine kinase, ALT, and AST were measured.

Patients were randomly allocated to simvastatin (60 mg) or control given via a nasogastric tube or orally from study inclusion to ICU discharge, death, or day 28, whichever occurred first. Simvastatin or control were started on the same day as antibiotic therapy for suspected VAP. The simvastatin dosage was halved in patients with renal failure (creatinine clearance <30 mL/min). A computer-generated random- number table was prepared by statisticians to assign patients in blocks of 4 to receive either simvastatin or control.

Block size was unknown to the investigators, who was enrolled the patients and then called the statistics department to obtain the randomization and treatment numbers after checking the inclusion and non-inclusion criteria Outcome The primary outcome was the day-28 mortality rate. Secondary outcomes were ICU mortality rates; number of days outside the ICU between day 1 and day 28; and number of ventilator-free days (after successful weaning) between day 1 and both day 28.

Successful weaning was defined as spontaneous breathing for at least 48 hours after disconnection of the ventilator.

• Study Type: Interventional
• Enrollment (Actual): 161
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11311
    • ain shams University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 27 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who suspected to had VAP defined as a modified Clinical Pulmonary Infection Score (CPIS) of at least 5 and if they underwent quantitative bacteriological cultures of bronchoalveolar lavage (BAL) fluid, a protected telescopic catheter (PTC), or an endotracheal aspirate. The modified CPIS is based on body temperature, blood leukocyte count, amount and appearance of tracheal secretions, ratio of partial pressure of oxygen (PaO2) to fraction of inspired oxygen, acute respiratory distress syndrome (ARDS), and infiltrates on chest radiography. The total can range from 1 to 10 points (Luna et al., 2003).
• Patients were included only for the first episode of suspected VAP.

Exclusion Criteria:

• o Statin therapy at intubation

  • Previous VAP episode during the same hospitalization
  • Known pregnancy
  • Immunodepression with bone marrow aplasia
  • Imminent death (Simplified Acute Physiology Score II of 75 or greater, calculated over the last 6 hours)
  • Treatment limitation decisions
  • Nothing-by-mouth order and no nasogastric tube, continuous gastric aspiration
  • Known chronic intestinal malabsorption
  • Known simvastatin hypersensitivity
  • Acute hepatic failure
  • Use of CYP3A4 inhibitors or cyclosporine
  • Creatine kinase level greater than 5 times the upper limit of normal
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels greater than 3 times the upper limit of normal

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: simvastatin group; 68 patients who had a ventilator associated pneumonia received simvastatin	Drug: Simvastatin; simvastatin 60 mg tab
No Intervention: control group; 68 patients who had a ventilator associated pneumonia not received simvastatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary outcome was the day-28 mortality rate.	asses effect of statin on mortality in ventilator associated pneumonia patient	28 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU mortality rates	rate of mortality of patients with ventilator associated pneumonia between simvastatin group and control group in intensive care unit	between day 1 and day 28
number of days outside the ICU between day 1 and day 28	the number of days patients who have improved spent outside the icu between day 1 and day 28	between day 1 and day 28
number of ventilator-free days (after successful weaning) between day 1 and both day 28.	number of days patient of the two group spent without ventilator in the intensive care unit between day 1 and day 28 after successful weaning. Successful weaning was defined as spontaneous breathing for at least 48 hours after disconnection of the ventilator.	between day 1 and day 28

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Principal Investigator: YOUSEF FAWZY, ain shams University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): December 20, 2021
• Study Completion (Actual): February 1, 2022

Study Registration Dates

• First Submitted: January 21, 2022
• First Submitted That Met QC Criteria: February 1, 2022
• First Posted (Actual): February 9, 2022

Study Record Updates

• Last Update Posted (Actual): February 9, 2022
• Last Update Submitted That Met QC Criteria: February 1, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Cross Infection; Iatrogenic Disease; Healthcare-Associated Pneumonia; Pneumonia; Pneumonia, Ventilator-Associated; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: EMASU M D 219 /2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No