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

Sponsor
Ain Shams University (Other)
Overall Status
Completed
CT.gov ID
NCT05230472
Collaborator
(none)
161
1
2
13
12.4

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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

  1. 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 Design

Study Type:
Interventional
Actual Enrollment :
161 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
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.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.
Masking:
Triple (Participant, Care Provider, Investigator)
Masking Description:
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.
Primary Purpose:
Prevention
Official Title:
Effect of Statin Therapy on Mortality in Patients With Ventilator Associated Pneumonia
Actual Study Start Date :
Jan 1, 2021
Actual Primary Completion Date :
Dec 20, 2021
Actual Study Completion Date :
Feb 1, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. The primary outcome was the day-28 mortality rate. [28 day]

    asses effect of statin on mortality in ventilator associated pneumonia patient

Secondary Outcome Measures

  1. ICU mortality rates [between day 1 and day 28]

    rate of mortality of patients with ventilator associated pneumonia between simvastatin group and control group in intensive care unit

  2. number of days outside the ICU between day 1 and day 28 [between day 1 and day 28]

    the number of days patients who have improved spent outside the icu between day 1 and day 28

  3. number of ventilator-free days (after successful weaning) between day 1 and both day 28. [between day 1 and 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
29 Years to 71 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Ain Shams University Cairo Egypt 11311

Sponsors and Collaborators

  • Ain Shams University

Investigators

  • Principal Investigator: YOUSEF FAWZY, Ain Shams University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Hanan Mahmoud Farag Awad, hananfarag@med.asu.edu.eg, Ain Shams University
ClinicalTrials.gov Identifier:
NCT05230472
Other Study ID Numbers:
  • EMASU M D 219 /2020
First Posted:
Feb 9, 2022
Last Update Posted:
Feb 9, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 9, 2022