Statin Therapy in Acute Influenza

• ClinicalTrials.gov Identifier: NCT02056340
• Recruitment Status: Completed
• First Posted: February 6, 2014
• Results First Posted: July 26, 2019
• Last Update Posted: July 26, 2019
• Sponsor: Beth Israel Deaconess Medical Center
• Collaborator: National Institute of General Medical Sciences (NIGMS)
• Information provided by (Responsible Party): Maureen Chase MD MPH, Principal Investigator, Beth Israel Deaconess Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Influenza	Drug: Atorvastatin; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Statin Therapy in Acute Influenza
• Actual Study Start Date: October 2013
• Actual Primary Completion Date: June 30, 2018
• Actual Study Completion Date: June 30, 2018

Arms and Interventions

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 Name: 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

Outcome Measures

Primary Outcome Measures :

1. Change in Inflammatory Markers From Time Zero to 72 Hours [ Time Frame: Baseline 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.

Secondary Outcome Measures :

1. Severity of Illness Score Baseline to 72 Hours [ Time Frame: Baseline and 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.

Other Outcome Measures:

1. Progression to Shock State [ Time Frame: From date of randomization until discharge from hospital ]
   The investigators will assess the effect of statin therapy on rates of development of shock state
2. Severity of Illness [ Time Frame: 24 hours post enrollment ]
   The investigators will assess the effect of statin therapy on APACHE II scores
3. In-hospital Mortality [ Time Frame: 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 ]
   The investigators will assess the effect of statin therapy on in-hospital mortality
4. ICU and Hospital Length of Stay [ Time Frame: 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 ]
   The investigators will assess the effect of statin therapy on hospital and ICU length of stay.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Massachusetts

The Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

Beth Israel Deaconess Medical Center

National Institute of General Medical Sciences (NIGMS)

Investigators

• Principal Investigator: Maureen Chase, MD, MPH; Beth Israel Deaconess Medical Center

  Study Documents (Full-Text)

Documents provided by Maureen Chase MD MPH, Principal Investigator, Beth Israel Deaconess Medical Center:

Study Protocol and Statistical Analysis Plan  [PDF] February 1, 2017

Informed Consent Form: Part D: Informed Consent  [PDF] February 3, 2016

Informed Consent Form: Verbal Consent - Rapid Antigen Test (RAT)  [PDF] December 30, 2015

More Information

• Responsible Party: Maureen Chase MD MPH, Principal Investigator, Maureen Chase MD MPH, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT02056340
• Other Study ID Numbers: 2013P000026; 1K23GM101463-01A1 ( U.S. NIH Grant/Contract ); FWA00003245 ( Other Identifier: BIDMC )
• First Posted: February 6, 2014
• Results First Posted: July 26, 2019
• Last Update Posted: July 26, 2019
• Last Verified: July 2019

Additional relevant MeSH terms:

Influenza, Human; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Atorvastatin; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors