Pilot Study of Atorvastatin for Orthopedic Surgery Patients (POST-OP Pilot)

June 2, 2017 updated by: Hospital for Special Surgery, New York

The Post-Operative Statin for Thromboprophylaxis & Cardiovascular Outcomes Protection (POST-OP) Pilot Trial

Up to 35% of hip fracture patients have been shown to experience heart injury after surgery, and as many as 10% have a heart attack or die in the three months after surgery. Hip and knee arthroplasty patients are also at risk of cardiovascular complications. Patients who have these complications have higher levels of inflammation postoperatively. Statins (such as atorvastatin/Lipitor) lower cholesterol and also lessen inflammation. Both of these effects are important in preventing heart attacks. Statins have been shown to reduce the risk of heart attacks in non-surgical patients, and to protect from heart attacks in patients having heart surgery. Whether statins can prevent heart attacks in orthopedic patients is not known.

In this pilot study the investigators will treat 30 orthopedic surgery patients (hip fracture, hip or knee arthroplasty) with either atorvastatin or placebo (a capsule with no study drug). Patients will start the study drug prior to surgery and take it for 45 days after surgery. Neither the doctors nor the patients will know whether they are taking atorvastatin or placebo. The investigators will look for evidence of inflammation and heart injury after surgery. The investigators hypothesize that atorvastatin will lessen the degree of postoperative inflammation found in these patients. In this study, the investigators will use a very sensitive test of heart injury that can detect problems even when patients have no symptoms. The investigators hypothesize that this test will demonstrate silent heart injury in over 50% of the hip fracture patients and over 30% of arthroplasty patients in our study.

The results of this trial will help us to develop a larger study in 1000 hip fracture and joint replacement patients to determine whether atorvastatin protects orthopedic surgery patients from heart injury and other complications of surgery.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

  • Thirty statin-naïve patients ≥ 65 years of age admitted to New York Presbyterian Hospital or Hospital for Special Surgery with an acute hip fracture, or for elective hip or knee arthroplasty will be randomized in a 1:1 ratio to atorvastatin 40 mg daily or matching placebo.
  • Atorvastatin will be initiated at least 4 hours prior to hip fracture surgery, or 4 days prior to arthroplasty, and will be continued until postoperative day (POD) 45.
  • Patients will be assessed daily in the hospital for adverse events.
  • Patients will be contacted by telephone weekly for four weeks after surgery and again on POD 45 and POD 90.
  • Patients will mail back study medication bottles on POD 45 for pill counts to assess compliance.
  • High sensitivity cardiac troponin I (hs-cTnI) will be measured pre-operatively (prior to atorvastatin therapy) and on POD 2.
  • High sensitivity C-reactive protein (hs-CRP), and a panel of cytokines (IL-1β, IL-2, IL-2r, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and soluble (s)CD-40L) will be measured preoperatively and on POD 2.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10021
        • Hospital for Special Surgery
      • New York, New York, United States, 10065
        • New York Presbyterian Hospital (Cornell)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years to 99 years (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Hip fracture or elective hip or knee arthroplasty
  • Age 65 years or older
  • Life expectancy > 3 months

Exclusion Criteria:

  • Pathological hip fracture due to cancer
  • Currently taking a statin, or took a statin within the last 30 days
  • Previous statin intolerance
  • Acute myocardial infarction or unstable angina
  • History of myocardial infarction, acute coronary syndrome, angina, coronary/arterial re-vascularization
  • Hip fracture patients with peripheral arterial disease
  • Hip fracture patients with history of stroke or transient ischemic attack.
  • Muscle disorder
  • Serious liver disease or alanine aminotransferase > 3x upper limit of normal
  • Serious renal disease (creatinine clearance <30cc/min)
  • Treatment with HIV protease inhibitor or Hepatitis C protease inhibitor
  • Treatment with erythromycin, clarithromycin, niacin or azole antifungal agent
  • Pregnant, planning to become pregnant, or breastfeeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Atorvastatin
Atorvastatin 40mg daily starting at least 4 hours prior to hip fracture surgery, or 4 days prior to hip or knee arthroplasty, and continued until postoperative day 45.
Drug: Atorvastatin
Atorvastatin or placebo will be started at least 4 hours prior to surgery, and continued nightly until postoperative day 45
Other Names:
  • Lipitor
Placebo Comparator: Sugar pill
Sugar pill (placebo) daily starting at least 4 hours prior to hip fracture surgery, or 4 days prior to hip or knee arthroplasty, and continued until postoperative day 45.
Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of All Enrolled Patients With a Peri-operative Rise in High-sensitivity Cardiac Troponin I
Time Frame: change from preoperative to postoperative day 2
The percentage of orthopedic patients with a ≥ 10 pg/mL rise in high-sensitivity cardiac troponin I (hs-cTnI) from baseline pre-operatively to post-operative day (POD)2
change from preoperative to postoperative day 2
Peri-operative Rise in High Sensitivity C-reactive Protein (Hs-CRP)
Time Frame: Change from preoperative to post-operative day 2
The change in the level of hs-CRP from baseline to POD2 in 20 orthopedic patients randomized (1:1) to atorvastatin 40mg versus placebo.
Change from preoperative to post-operative day 2

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peri-operative Rise in Interleukin-6 (IL-6) Levels
Time Frame: Change from preoperative to postoperative day 2
The change in the level of IL-6 from baseline to POD2 in 16 arthroplasty patients randomized (1:1) to atorvastatin 40mg versus placebo.
Change from preoperative to postoperative day 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital for Special Surgery, New York

Collaborators

Washington University School of Medicine
Weill Medical College of Cornell University
University of Utah

Investigators

  • Principal Investigator: Anne R Bass, MD, Hospital for Special Surgery, New York

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2014

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

January 1, 2017

Study Registration Dates

First Submitted

July 21, 2014

First Submitted That Met QC Criteria

July 21, 2014

First Posted (Estimate)

July 22, 2014

Study Record Updates

Last Update Posted (Actual)

July 2, 2017

Last Update Submitted That Met QC Criteria

June 2, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EPAR4398
  • UL1TR000457-06 (NIH)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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