Clinical trial NCT02681653: Study the Impact of Statins in Septic Shock
Official title: Prospective Randomized Study to Assess Impact of Statins in Septic Shock
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Septic Shock
Keywords: Statins
Septic Shock
Lead sponsor: Sanjay Gandhi Postgraduate Institute of Medical Sciences
Sponsor class: OTHER_GOV
First posted: 2016-02-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 description: 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 recorded simultaneously. Severity scores, event free days (vasopressor, ventilation, dialysis, transfusion, parenteral nutrition), and mortality after 28 days of inclusion in study will be recorded.

Ethical Issues:

Written informed consent will be taken from either the patient (if possible) or from the primary decision maker related to the patient.

Study population:

A total of 80 patients of septic shock admitted in ICU will be enrolled into this study. Patients either admitted with septic shock or who develop septic shock during their stay in ICU will be eligible for inclusion into the study. The statin and placebo group will have 40 patients each.

Eligibility criteria: Inclusion Criteria:

* Clinical disease of septic shock
* Aged eighteen years and above
* Admitted to ICU

Exclusion Criteria:

* Previous statin induced myopathy or hypersensitivity reaction
* Greater than two and half times elevated liver transaminases
* Chronic liver disease
* Pregnant or lactating mothers

Primary outcomes:
measure: Mortality
timeFrame: 28 day of ICU stay
Secondary outcomes:
measure: Cytokines in septic shock
timeFrame: Day 1, 4 and 7 of commencement of trial drug.
measure: Vasopressor free days.
timeFrame: 28 days after commencement of trial drug.
measure: Ventilation free days.
timeFrame: 28 days after commencement of trial drug.
measure: Renal replacement free days.
timeFrame: 28 days after commencement of trial drug.
measure: Transfusion free days.
timeFrame: 28 days after commencement of trial drug.
measure: Total parenteral nutrition free days.
timeFrame: 28 days after commencement of trial drug.
Other outcomes:
Locations:
city: Lucknow
country: India
facility: Department of Immunology, SGPGIMS
state: UP
city: Lucknow
country: India
facility: Department of Critical Care Medicine
state: Uttar Pradesh
Study officials:
affiliation: Sanjay Gandhi Post Graduate Institute of Medical Sciences
name: Ratender K Singh, MD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Singh RK, Agarwal V, Baronia AK, Kumar S, Poddar B, Azim A. The Effects of Atorvastatin on Inflammatory Responses and Mortality in Septic Shock: A Single-center, Randomized Controlled Trial. Indian J Crit Care Med. 2017 Oct;21(10):646-654. doi: 10.4103/ijccm.IJCCM_474_16.