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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2015 by Hospital for Special Surgery, New York
Sponsor:
Information provided by (Responsible Party):
Hospital for Special Surgery, New York
ClinicalTrials.gov Identifier:
NCT02197065
First received: July 21, 2014
Last updated: April 27, 2015
Last verified: April 2015
  Purpose

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.


Condition Intervention Phase
Hip Fracture
Myocardial Ischemia
Inflammation
Drug: Atorvastatin
Drug: Placebo
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Hospital for Special Surgery, New York:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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.


Estimated Enrollment: 30
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)
Arms Assigned Interventions
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 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.
Drug: Placebo

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

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02197065

Contacts
Contact: Anne R Bass, MD (212) 774-7043 bassa@hss.edu
Contact: Brian F Gage, MD MSc (314) 454-8697 BGAGE@im.wustl.edu

Locations
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   
Sponsors and Collaborators
Hospital for Special Surgery, New York
Investigators
Principal Investigator: Anne R Bass, MD Hospital for Special Surgery, New York
  More Information

No publications provided

Responsible Party: Hospital for Special Surgery, New York
ClinicalTrials.gov Identifier: NCT02197065     History of Changes
Other Study ID Numbers: EPAR4398, UL1TR000457-06
Study First Received: July 21, 2014
Last Updated: April 27, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Hospital for Special Surgery, New York:
hip fracture
myocardial ischemia
statin
surgery
troponin
complication
arthroplasty
hip
knee
orthopedic
atorvastatin
cardiovascular

Additional relevant MeSH terms:
Coronary Artery Disease
Hip Fractures
Inflammation
Myocardial Ischemia
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Coronary Disease
Femoral Fractures
Fractures, Bone
Heart Diseases
Hip Injuries
Leg Injuries
Pathologic Processes
Vascular Diseases
Wounds and Injuries
Atorvastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on May 26, 2015