Pilot Study of Atorvastatin for Orthopedic Surgery Patients

Inflammation Clinical Trial

— POST-OP Pilot  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02197065
• Other study ID #: EPAR4398
• Secondary ID: UL1TR000457-06
• Status: Completed
• Phase: Phase 2
• First received: July 21, 2014
• Last updated: February 28, 2017
• Start date: September 2014
• Est. completion date: July 2016

Study information

• Verified date: February 2017
• Source: Hospital for Special Surgery, New York
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

• Rho-associated, coiled-coil containing protein kinase 1 (ROCK) activity in peripheral blood mononuclear cell will be measured preoperatively and on POD 2.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Hip Fracture
• Hip Fractures
• Inflammation
• Ischemia
• Myocardial Ischemia

Intervention

Drug:
• Atorvastatin
Atorvastatin or placebo will be started at least 4 hours prior to surgery, and continued nightly until postoperative day 45
• Placebo

Locations

Country	Name	City	State
United States	Hospital for Special Surgery	New York	New York
United States	New York Presbyterian Hospital (Cornell)	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Hospital for Special Surgery, New York

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Peri-operative rise in rho-kinase activity	We will measure rho-kinase (ROCK) activity in peripheral blood mononuclear cells collected before statin administration and on postoperative day 2 in 30 orthopedic patients randomized (1:1) to atorvastatin 40mg versus placebo.	Prior to surgery and post-operative day 2
Primary	Percentage of patients with a peri-operative rise in high-sensitivity cardiac troponin I level	We will measure high-sensitivity cardiac troponin I (hs-cTnI) at the time of recruitment pre-operatively and on post-operative day (POD) 2 in 30 orthopedic patients.	Prior to surgery and post-operative day 2
Secondary	Peri-operative rise in high sensitivity C-reactive protein (hs-CRP)	We will measure hs-CRP before statin administration, and on POD2 in 30 orthopedic patients randomized (1:1) to atorvastatin 40mg versus placebo.	Prior to surgery and post-operative day 2