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

VAP - Ventilator Associated Pneumonia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05230472
• Other study ID #: EMASU M D 219 /2020
• Status: Completed
• Phase: Phase 4
• Start date: January 1, 2021
• Est. completion date: February 1, 2022

Study information

• Verified date: February 2022
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 161
• Est. completion date: February 1, 2022
• Est. primary completion date: December 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 29 Years to 71 Years

Eligibility

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

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Ventilator-Associated
• VAP - Ventilator Associated Pneumonia

Intervention

Drug:
• Simvastatin
simvastatin 60 mg tab

Locations

Country	Name	City	State
Egypt	Ain Shams University	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary outcome was the day-28 mortality rate.	asses effect of statin on mortality in ventilator associated pneumonia patient	28 day
Secondary	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
Secondary	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
Secondary	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