Clinical Trial: Study the Impact of Statins in Septic Shock

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Prospective Randomized Study to Assess Impact of Statins in Septic Shock

Brief Summary:

Sepsis is a common, expensive, frequently fatal and highly complex inflammatory syndrome wherein multiple cellular and humoral pathways are involved. Since it's a multifactorial syndrome merely blocking one of the various inflammatory pathways may not suffice to provide effective treatment and this may partly explain why most of the adjunctive therapies developed for severe sepsis have yielded disappointing results in rigorous clinical trials. Statins have varied pleiotropic effects on the inflammatory mediators and there addition to the current adjuvant therapies in septic shock may help in reduction of mortality. The present trial aims to study survival benefit and changes in bio-marker levels in septic shock.

Adult patients (>=18 years) in septic shock and admitted to ICU will be included in the study. Patients will be randomized as per computer generated random number into the Drug (Atorvastatin, 40 mg) or matched placebo group. Drug or placebo will be given to selected patient via nasogastric tube for 7 days. Bio markers (Il-6, TNF-alpha) estimated during the trial week (Days 1, 4, and 7). All clinical and study personnel and patients remained blinded to the study group assignment throughout the trial.


Detailed Summary:

Objectives:

  • Study impact of statins on levels of biomarkers (IL-6 and TNF-α) of sepsis.
  • Study survival benefit of statins in septic shock.

Introduction:

Sepsis is the leading cause of mortality in non-coronary ICUs. Mortality associated with sepsis is still considerably high. Rising economic burden of managing sepsis is a major concern. Statin is an anti-hyperlipidemic drug with pleiotropic effects. It has properties like anti-inflammatory/oxidative, immunomodulatory effects, enhances endothelial function, reduction in blood thrombogenicity, and increased nitric oxide (NO) bioavailability. Available evidence suggests that statins may play a positive role in reduction of mortality in sepsis. However, the multidimensional heterogeneous character of the available studies does not allow drawing firm conclusions about its usefulness in sepsis and septic shock. This randomized, double blinded, placebo controlled trial is an attempt to study the impact of statins on mortality and biomarker levels in septic shock.

Details of material and methods:

Patients >= age 18 yrs meeting the American European consensus conference definition of septic shock will be enrolled into the study. After the written informed consent from the primary decision maker the patients will be randomized into either the drug or placebo group. Each group will either receive Atorvastatin 40mg or a matched placebo for 7 days. IL-6 and TNF alpha levels will be estimated on D1, D4 and D7 of the trial week. Relevant clinical and laboratory (clinical biochemistry, hematological, coagulation parameters, LFT and renal function tests) will be
Sponsor: Sanjay Gandhi Postgraduate Institute of Medical Sciences

Current Primary Outcome: Mortality [ Time Frame: 28 day of ICU stay ]

28 day mortality after inclusion in study.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Cytokines in septic shock [ Time Frame: Day 1, 4 and 7 of commencement of trial drug. ]
    IL-6, TNF-α levels on Day 1, 4 and 7.
  • Vasopressor free days. [ Time Frame: 28 days after commencement of trial drug. ]
    Vasopressor free days during septic shock.
  • Ventilation free days. [ Time Frame: 28 days after commencement of trial drug. ]
    Ventilation free days during septic shock.
  • Renal replacement free days. [ Time Frame: 28 days after commencement of trial drug. ]
    Renal replacement free days during septic shock.
  • Transfusion free days. [ Time Frame: 28 days after commencement of trial drug. ]
    Transfusion free days during septic shock.
  • Total parenteral nutrition free days. [ Time Frame: 28 days after commencement of trial drug. ]
    Total parenteral nutrition free days during septic shock.


Original Secondary Outcome: Same as current

Information By: Sanjay Gandhi Postgraduate Institute of Medical Sciences

Dates:
Date Received: September 15, 2015
Date Started: January 2012
Date Completion:
Last Updated: February 11, 2016
Last Verified: December 2015