Pilot Study of Atorvastatin for Orthopedic Surgery Patients (POST-OP Pilot)
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 Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||The Post-Operative Statin for Thromboprophylaxis & Cardiovascular Outcomes Protection (POST-OP) Pilot Trial|
- Percentage of patients with a peri-operative rise in high-sensitivity cardiac troponin I level [ Time Frame: Prior to surgery and post-operative day 2 ] [ Designated as safety issue: Yes ]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.
- Peri-operative rise in high sensitivity C-reactive protein (hs-CRP) [ Time Frame: Prior to surgery and post-operative day 2 ] [ Designated as safety issue: No ]We will measure hs-CRP before statin administration, and on POD2 in 30 orthopedic patients randomized (1:1) to atorvastatin 40mg versus placebo.
- Peri-operative rise in rho-kinase activity [ Time Frame: Prior to surgery and post-operative day 2 ] [ Designated as safety issue: No ]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.
|Study Start Date:||September 2014|
|Estimated Study Completion Date:||September 2016|
|Estimated Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
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.
Atorvastatin or placebo will be started at least 4 hours prior to surgery, and continued nightly until postoperative day 45
Other Name: 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02197065
|Contact: Anne R Bass, MD||(212) firstname.lastname@example.org|
|Contact: Brian F Gage, MD MSc||(314) 454-8697||BGAGE@im.wustl.edu|
|United States, New York|
|Hospital for Special Surgery||Recruiting|
|New York, New York, United States, 10021|
|Contact: Fein Arielle, BA 212-774-7043 FeinA@hss.edu|
|Contact: Anne R Bass, MD 212-774-7043 BassA@hss.edu|
|New York Presbyterian Hospital (Cornell)||Recruiting|
|New York, New York, United States, 10065|
|Contact: Arielle Fein, BA 212-774-7043 FeinA@hss.edu|
|Contact: Anne R Bass, MD 2127747043 BassA@hss.edu|
|Principal Investigator:||Anne R Bass, MD||Hospital for Special Surgery, New York|