Pilot Study of Atorvastatin for Orthopedic Surgery Patients

NCT02197065 | Completed Phase 2 Results

• 2 other identifiers: EPAR4398UL1TR000457-06
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

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.

Conditions

Hip Fracture; Myocardial Ischemia; Inflammation

Keywords

hip fracture; myocardial ischemia; statin; surgery; troponin; complication; arthroplasty; hip; knee; orthopedic; atorvastatin; cardiovascular

Outcome Measures

Primary Outcomes (2)

• Percentage of All Enrolled Patients With a Peri-operative Rise in High-sensitivity Cardiac Troponin I

  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)

  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 Outcomes (1)

• Peri-operative Rise in Interleukin-6 (IL-6) Levels

  Change from preoperative to postoperative day 2

Study Arms (2)

Atorvastatin

EXPERIMENTAL

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

Sugar pill

PLACEBO COMPARATOR

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

Interventions

Atorvastatin DRUG

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

Also known as: Lipitor

Atorvastatin

Placebo DRUG

Sugar pill

Eligibility Criteria

• Age: 65 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospital for Special Surgery, New York: lead
• Weill Medical College of Cornell University: collaborator
• Washington University School of Medicine: collaborator
• University of Utah: collaborator

Study Sites (2)

Hospital for Special Surgery

New York, New York, 10021, United States

Location

New York Presbyterian Hospital (Cornell)

New York, New York, 10065, United States

Location

Related Publications (1)

• 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.

  PMID: 29398998 DERIVED

MeSH Terms

Conditions

Hip Fractures; Myocardial Ischemia; Inflammation

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Femoral Fractures; Fractures, Bone; Wounds and Injuries; Hip Injuries; Leg Injuries; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Limitations and Caveats

Small sample size: recruitment was made difficult by comorbidities in hip fracture patients that limited participation, the reluctance of arthroplasty patients to enroll in an interventional trial, and statin use in 40% of the target population.

Results Point of Contact

• Title: Anne R. Bass, MD
• Organization: Hospital for Special Surgery

bassa@hss.edu

212-774-7043

Study Officials

• Anne R Bass, MD

  Hospital for Special Surgery, New York

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2014
• First Posted: July 22, 2014
• Study Start: September 1, 2014
• Primary Completion: July 1, 2016
• Study Completion: January 1, 2017
• Last Updated: July 2, 2017
• Results First Posted: July 2, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)