Clinical trial NCT02197065: Pilot Study of Atorvastatin for Orthopedic Surgery Patients
Official title: The Post-Operative Statin for Thromboprophylaxis & Cardiovascular Outcomes Protection (POST-OP) Pilot Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hip Fracture
Myocardial Ischemia
Inflammation
Keywords: hip fracture
myocardial ischemia
statin
surgery
troponin
complication
arthroplasty
hip
knee
orthopedic
atorvastatin
cardiovascular
Lead sponsor: Hospital for Special Surgery, New York
Sponsor class: OTHER
Collaborators: name: Weill Medical College of Cornell University
name: Washington University School of Medicine
name: University of Utah
First posted: 2014-07-22
Enrollment: 20
Sex: ALL
Minimum age (years): 65
Maximum age (years): 99
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of All Enrolled Patients With a Peri-operative Rise in High-sensitivity Cardiac Troponin I
timeFrame: change from preoperative to postoperative day 2
measure: Peri-operative Rise in High Sensitivity C-reactive Protein (Hs-CRP)
timeFrame: Change from preoperative to post-operative day 2
Secondary outcomes:
measure: Peri-operative Rise in Interleukin-6 (IL-6) Levels
timeFrame: Change from preoperative to postoperative day 2
Other outcomes:
Locations:
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital (Cornell)
state: New York
Study officials:
affiliation: Hospital for Special Surgery, New York
name: Anne R Bass, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bass AR, Szymonifka JD, Rondina MT, Bogardus M, Scott MG, Woller SC, Stevens SM, Eby C, Merritt K, Valle AGD, Moskowitz G, Flores E, Gage BF. Postoperative Myocardial Injury and Inflammation Is Not Blunted by a Trial of Atorvastatin in Orthopedic Surgery Patients. HSS J. 2018 Feb;14(1):67-76. doi: 10.1007/s11420-017-9577-1. Epub 2017 Oct 13.