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

NCT ID: NCT05230472

Last Updated: 2022-02-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 161 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-01
• Study Completion Date: 2022-02-01

Brief 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.

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.

Conditions

VAP - Ventilator Associated Pneumonia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

simvastatin group

68 patients who had a ventilator associated pneumonia received simvastatin

Group Type: ACTIVE_COMPARATOR

Simvastatin

Intervention Type: DRUG

simvastatin 60 mg tab

control group

68 patients who had a ventilator associated pneumonia not received simvastatin

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Simvastatin

simvastatin 60 mg tab

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 29 Years
• Maximum Eligible Age: 71 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ain Shams University

OTHER

Sponsor Role: lead

Responsible Party

Hanan Mahmoud Farag Awad

hananfarag@med.asu.edu.eg

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

YOUSEF FAWZY

Role: PRINCIPAL_INVESTIGATOR

Ain Shams University

Locations

Ain Shams University

Cairo, , Egypt

Countries

Egypt

Other Identifiers

EMASU M D 219 /2020

Identifier Type: -

Identifier Source: org_study_id