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CompletedNCT02197065POST-OP PilotUpdated Jul 2, 2017Results posted

Pilot Study of Atorvastatin for Orthopedic Surgery Patients

A Phase 2 interventional study of Atorvastatin and Placebo in Hip Fracture, Myocardial Ischemia and Inflammation, sponsored by Hospital for Special Surgery, New York. Completed at 2 sites in United States. Open to participants aged 65 Years to 99 Years. Per ClinicalTrials.gov, last updated 2017-07-02.

Sponsored by Hospital for Special Surgery, New York · Phase 2, Interventional, and Prevention

Phase
Phase 2
Study type
Interventional
Enrollment
20
Allocation
Randomized
Ages
65 Years to 99 Years
Sex
All
01

Study 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.

Read the 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.
02

Conditions studied

  • Hip Fracture
  • Myocardial Ischemia
  • Inflammation

Keywords

  • hip fracture
  • myocardial ischemia
  • statin
  • surgery
  • troponin
  • complication
  • arthroplasty
  • hip
  • knee
  • orthopedic
  • atorvastatin
  • cardiovascular
03

In context

Myocardial Ischemia

3,232 studies on the registry are indexed under Myocardial Ischemia; 395 are open to participants now.

This study's enrollment of 20 is below the median of 120 across 1,895 interventional studies indexed under Myocardial Ischemia.

Browse Myocardial Ischemia studies →

Lead sponsor

Hospital for Special Surgery, New York is the lead sponsor of 217 studies on the registry; 39 are open to participants now.

Of its 27 completed or terminated interventional studies of FDA-regulated products, 20 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
65 Years to 99 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

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

Exclusion criteria

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
05

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
20 participants (actual)

Study arms

  • 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

  • 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

Interventions

  • DrugAtorvastatin

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

    Also known as: Lipitor

  • DrugPlacebo
06

What researchers measure

Primary outcomes

  1. 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

    Time frame: change from preoperative to postoperative day 2

  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.

    Time frame: Change from preoperative to post-operative day 2

Secondary outcomes

  1. Peri-operative Rise in Interleukin-6 (IL-6) Levels

    The change in the level of IL-6 from baseline to POD2 in 16 arthroplasty patients randomized (1:1) to atorvastatin 40mg versus placebo.

    Time frame: Change from preoperative to postoperative day 2

07

Results

Posted Jul 2, 2017
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.

Participant flow

Participant flow — Overall Study
MilestoneAtorvastatinSugar Pill
Started1010
Completed1010
Not completed00

Outcome measures

PrimaryPercentage 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

Time frame:
change from preoperative to postoperative day 2
Reported as:
Number · percentage of patients
Percentage of All Enrolled Patients With a Peri-operative Rise in High-sensitivity Cardiac Troponin I
percentage of patientsAll Patients
Percentage of All Enrolled Patients With a Peri-operative Rise in High-sensitivity Cardiac Troponin I20
Statistical analysis
  • All Patients · Proportion: 0.2
PrimaryPeri-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.

Time frame:
Change from preoperative to post-operative day 2
Reported as:
Median · mg/L
Peri-operative Rise in High Sensitivity C-reactive Protein (Hs-CRP)
mg/LAtorvastatinSugar Pill
Peri-operative Rise in High Sensitivity C-reactive Protein (Hs-CRP)98.95 (63.8 to 151.4)85.95 (52.85 to 124.9)
Statistical analysis
  • Atorvastatin vs Sugar Pill · Wilcoxon (Mann-Whitney) · p = 0.58 · Median difference (final values): 13
SecondaryPeri-operative Rise in Interleukin-6 (IL-6) Levels

The change in the level of IL-6 from baseline to POD2 in 16 arthroplasty patients randomized (1:1) to atorvastatin 40mg versus placebo.

Time frame:
Change from preoperative to postoperative day 2
Reported as:
Median · pg/mL
Peri-operative Rise in Interleukin-6 (IL-6) Levels
pg/mLAtorvastatinSugar Pill
Peri-operative Rise in Interleukin-6 (IL-6) Levels1.28 (0.09 to 1.58)0.98 (0.53 to 1.45)
Statistical analysis
  • Atorvastatin vs Sugar Pill · Wilcoxon (Mann-Whitney) · p = 1.00 · Median difference (final values): 0.3

Adverse events

Collected over 90 days. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Atorvastatin0/10 (0%)1/10 (10%)3/10 (30%)
Sugar Pill0/10 (0%)2/10 (20%)5/10 (50%)
Most frequent serious events
Most frequent serious events
EventAtorvastatinSugar Pill
deep vein thrombosisVascular disorders1/100/10
HypertensionCardiac disorders1/100/10
bacteremiaInfections and infestations0/101/10
deliriumNervous system disorders0/101/10
alcohol withdrawalMetabolism and nutrition disorders0/101/10
fluid overloadCardiac disorders0/101/10
Most frequent other events
Most frequent other events
EventAtorvastatinSugar Pill
InfectionInfections and infestations3/102/10
deliriumNervous system disorders2/102/10
HypertensionCardiac disorders1/101/10
BradycardiaCardiac disorders1/100/10
neuropathyNervous system disorders0/101/10
pruritisSkin and subcutaneous tissue disorders0/101/10

Baseline characteristics

Age, Continuous
Age, Continuous(years)AtorvastatinSugar PillTotal
Median71 (67 to 76)75 (72 to 84)73 (70 to 82)
Sex: Female, Male
Sex: Female, Male(Participants)AtorvastatinSugar PillTotal
Female8614
Male246
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)AtorvastatinSugar PillTotal
Hispanic or Latino000
Not Hispanic or Latino101020
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)AtorvastatinSugar PillTotal
American Indian or Alaska Native000
Asian101
Native Hawaiian or Other Pacific Islander000
Black or African American011
White9918
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)AtorvastatinSugar PillTotal
United States101020
Orthopedic procedure
Orthopedic procedure(Participants)AtorvastatinSugar PillTotal
Knee arthroplasty246
Hip arthroplasty6410
Hip fracture repair224
08

Study locations

2 sites
  • Hospital for Special Surgery
    New York, New York 10021, United States
  • New York Presbyterian Hospital (Cornell)
    New York, New York 10065, United States
09

References and documents

Publications

  • 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. PubMed 29398998 ↗

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 2, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02197065
Lead sponsor
Hospital for Special Surgery, New York
Collaborators
Weill Medical College of Cornell University, Washington University School of Medicine, University of Utah
Responsible party
Sponsor
First posted
Jul 22, 2014
Start date
Sep 2014
Primary completion
Jul 2016
Completion
Jan 2017
Results posted
Jul 2, 2017
Last update
Jul 2, 2017

Study contacts

Anne R Bass, MD
principal investigator · Hospital for Special Surgery, New York

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Apr 2017. You cannot join it, but the record below documents what was studied.

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