Statin Therapy in Acute Influenza

Influenza (the 'flu') is a common virus infecting approximately 5-20% of the population in the United States and causing as many as 500,000 deaths worldwide each year. Currently, there are only a few treatments for influenza infection and none of these target inflammation that can be caused by the virus. This study will test whether the anti-inflammatory effects of statins, a class of drugs most often used to treat high cholesterol, will decrease the severity of illness in patients who are infected with influenza by testing markers of inflammation in the blood and recording resolution of influenza illness.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Drug: Placebo; Drug: Atorvastatin

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • The Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:(all must be present):

1. Adult patient (age > 18 years)
2. Positive influenza DFA/RAT test result
3. <12 hours from positive influenza test result

Exclusion Criteria:

1. Prior statin medication use (within 30 days of positive influenza test result)
2. Comfort measures only designation or anticipated withdrawal of life-support

3. Atorvastatin specific exclusions:

   1. Documented liver cirrhosis or liver dysfunction (AST or ALT greater than 240)
   2. Known allergy or intolerance to statins
   3. Rhabdomyolysis (CPK elevation > 6x normal)
   4. Patients taking the following medications: cyclosporine, HIV protease inhibitors, hepatitis C protease inhibitor telaprevir, fibric acid derivatives (gemfibrozil), niacin, azole antifungals (itraconazole, ketoconazole) clarithromycin and colchicine
4. Patients unable to take oral or nasogastric medications or plan for no oral intake as part of medical course (eg. emergent surgical intervention)
5. Known pregnancy or active breastfeeding
6. Inability to provide written informed consent for any reason

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Atorvastatin; Patients will be administered study medication (atorvastatin 40 mg) orally once daily for 5 days, for a maximum of 7 days for those who remain hospitalized.	Drug: Atorvastatin; Other Names: Lipitor
Placebo Comparator: Placebo; Patients will be administered study medication (matched placebo) orally once daily for 5 days, for a maximum of 7 days for those who remain hospitalized.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Inflammatory Markers From Time Zero to 72 Hours	The primary IL- 6 measurements were at time zero and at 72 hours. Analysis was performed using a linear mixed effects model to make use of all biomarker timepoints as hospitalized patients had biomarkers measured at additional timepoints.	Baseline to 72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of Illness Score Baseline to 72 Hours	Composite score for 5 major symptoms (fever, cough, sore throat, headache, myalgia) ranked from 0 to 3 (none, mild, moderate, severe) for a score ranging from 0 to 15. Higher scores reflect more severe symptoms.	Baseline and 72 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression to Shock State	The investigators will assess the effect of statin therapy on rates of development of shock state	From date of randomization until discharge from hospital
Severity of Illness	The investigators will assess the effect of statin therapy on APACHE II scores	24 hours post enrollment
In-hospital Mortality	The investigators will assess the effect of statin therapy on in-hospital mortality	From date of randomization until the date of first documented discharge from hospital or date of death from any cause, whichever came first, assessed up to 1 year
ICU and Hospital Length of Stay	The investigators will assess the effect of statin therapy on hospital and ICU length of stay.	From date of randomization until the date of ICU discharge (in the event of ICU admission) and/or hospital discharge, based on an estimated average of 30 days

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Maureen Chase, MD, MPH, Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2013
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): June 30, 2018

Study Registration Dates

• First Submitted: October 15, 2013
• First Submitted That Met QC Criteria: February 4, 2014
• First Posted (Estimate): February 6, 2014

Study Record Updates

• Last Update Posted (Actual): July 26, 2019
• Last Update Submitted That Met QC Criteria: July 25, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: 2013P000026; 1K23GM101463-01A1 (U.S. NIH Grant/Contract); FWA00003245 (Other Identifier: BIDMC)