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Study of Atorvastatin Versus Placebo to Reduce Cardiopulmonary Complications After Thoracic Surgery

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ClinicalTrials.gov Identifier: NCT00375518
Recruitment Status : Completed
First Posted : September 13, 2006
Results First Posted : January 22, 2016
Last Update Posted : January 6, 2021
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE September 11, 2006
First Posted Date  ICMJE September 13, 2006
Results First Submitted Date  ICMJE December 16, 2015
Results First Posted Date  ICMJE January 22, 2016
Last Update Posted Date January 6, 2021
Study Start Date  ICMJE July 2006
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 16, 2015)
Determine the Postoperative Complications Found in Each Group [ Time Frame: one week (minimum of 5 days) before surgery and continued for one week (minimum of 5 days) after surgery ]
To determine whether one week of preventive therapy with atorvastatin prior to surgery and one week after surgery reduced the composite rate of cardiovascular morbidity when compared to placebo.
Original Primary Outcome Measures  ICMJE
 (submitted: September 12, 2006)
  • Prospective, randomized, double-blind, placebo controlled study to determine whether
  • one week of preventive therapy with atorvastatin (n=240) prior to surgery and one week
  • after surgery reduced the rate of AF when compared to placebo (n=240). . (Other
  • cardiovascular events to be recorded: acute coronary syndrome, myocardial infarction,
  • cerebrovascular accident and pulmonary embolism).
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2006)
  • Exploratory study to determine whether one week of preventive therapy with atorvastatin
  • (n=240) prior to surgery and one week 5 days) after surgery reduced the rate of
  • pulmonary complications when compared to placebo (n=240) and attenuated
  • inflammatory and oxidative (CRP, IL-6, TNF and MPO) markers. Exploratory study to examine the relationship of SNP mutations in inflammatory marker
  • genes as well as in genes linked to be associated with AF. Exploratory study to examine the relationship of an imbalance in MMP-1/TIMP-1 ratio
  • and occurrence of postoperative AF and/or pulmonary complications.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Atorvastatin Versus Placebo to Reduce Cardiopulmonary Complications After Thoracic Surgery
Official Title  ICMJE Double-Blind Study of Atorvastatin Versus Placebo to Reduce Cardiopulmonary Complications After Thoracic Surgery
Brief Summary This study will compare atorvastatin (Lipitor) with a placebo (inactive pill) to see if this drug reduces heart rhythm abnormalities (arrhythmias) or lung inflammation after thoracic surgery. Preliminary results suggest that cholesterol lowering drugs (statins) may reduce problems after surgery such as arrhythmias or lung inflammation which may be serious. This study will be randomized and double blind, meaning that patients are placed in groups purely by chance, like flipping a coin. Neither the patient or doctor will know which group the patient is in.
Detailed Description

Hypothesis: Statins attenuate perioperative inflammatory and oxidative mechanisms that contribute to the initiation and severity of cardiopulmonary complications after thoracic surgery.

Aim 1. To determine whether prophylactic administration of atorvastatin attenuates the inflammatory and oxidative response to surgery and significantly reduces the composite risk of cardiovascular morbidity (atrial fibrillation (AF), acute coronary syndrome, myocardial infarction (MI), cerebrovascular accident (CVA), pulmonary embolism) and mortality within 30 days after thoracic surgery.

Aim 2. To explore whether prophylactic administration of atorvastatin attenuates the inflammatory and oxidative (CRP, IL-6, TNF, and MPO) response to surgery and significantly reduces the overall risk of pulmonary complications (atelectasis, pneumonia, pneumonitis, acute respiratory failure) after thoracic surgery.

Aim 3. To explore the association of single nucleotide polymorphism (SNP) changes in genes linked to atrial fibrillation and inflammatory markers and development of pulmonary morbidity after thoracic surgery.

Aim 4. To explore whether an imbalance between metalloproteinase (MMP)-1 and its inhibitor (TIMP) is associated with postoperative atrial fibrillation risk and/or development of pulmonary morbidity after thoracic surgery.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Thoracic Surgery
Intervention  ICMJE
  • Drug: Atorvastatin
    Atorvastatin 40 mg once a day beginning 7 days before the operation. Surgical procedures will be as planned and unaffected by this study. Starting from the day after surgery, patients will be given their study drug for an additional 7 days.
  • Drug: Placebo
    Placebo given beginning 7 days before the operation. Starting from the day after surgery, patients will be given their study drug for an additional 7 days.
Study Arms  ICMJE
  • Active Comparator: 1
    Atorvastatin
    Intervention: Drug: Atorvastatin
  • Placebo Comparator: 2
    placebo
    Intervention: Drug: Placebo
Publications * Amar D, Park B, Zhang H, Shi W, Fleisher M, Thaler HT, Rusch VW. Beneficial effects of perioperative statins for major pulmonary resection. J Thorac Cardiovasc Surg. 2015 Jun;149(6):1532-8. doi: 10.1016/j.jtcvs.2014.12.016. Epub 2014 Dec 18.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 23, 2010)
162
Original Enrollment  ICMJE
 (submitted: September 12, 2006)
480
Actual Study Completion Date  ICMJE May 2014
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adult patients ≥ 18 yr. scheduled for anatomic lung resection (segmentectomy, lingulectomy, possible or definite lobectomy, bilobectomy, pneumonectomy or extrapleural pneumonectomy) with or without chest wall resection or limited resection
  • Patients with regular cardiac rhythm
  • Patients able to take oral capsules
  • Patients capable of providing written, informed consent
  • Patients without known hepatic or kidney disease

Exclusion Criteria:

  • Patients already taking any statin, gemfibrozil (Lopid), or ezetimibe (Zetia)
  • Hypersensitivity to atorvastatin
  • Chronic atrial fibrillation
  • Patients already taking class Ic or III antiarrhythmic drugs
  • Known pregnancy a urine pregnancy test will be given to women of childbearing age
  • Known history of active hepatic disease or known hepatic insufficiency
  • Known history of active kidney disease or insufficiency
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00375518
Other Study ID Numbers  ICMJE 06-079
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: David Amar, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP