Official Title: “Double-Blind Study of Atorvastatin Versus Placebo to Reduce Cardiopulmonary Complications After Thoracic Surgery”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Factorial Assignment, Safety/Efficacy Study

Study Primary Completion Date: July 2009

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.

Intervention(s) in this Clinical Trial

• 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.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Atorvastatin
• Placebo Comparator: 2
  • placebo

Primary Measures

• To determine whether one week of preventive therapy with atorvastatin (n=240) prior to surgery and one week after surgery reduced the composite rate of cardiovascular morbidity when compared to placebo.
  • Time Frame: one week (minimum of 5 days) before surgery and continued for one week (minimum of 5 days) after surgery
    Safety Issue?: Yes

Secondary Measures

• To determine whether one week of preventive therapy with atorvastatin (n=240) reduced the rate of pulmonary complications when compared to placebo and attenuated inflammatory and oxidative markers.
  • Time Frame: prior to surgery and one week 5 days)after surgery
    Safety Issue?: Yes

Inclusion Criteria:

• Adult patients > 55 years old scheduled for lung resection (possible or efinite lobectomy, bilobectomy, pneumonectomy, or extrapleural pneumonectomy) with or without chest wall 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 (unlikely with > 55 year cutoff with menopause, no required testing)
• Known history of active hepatic disease or known hepatic insufficiency
• Known history of active kidney disease or insufficiency

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 56 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Memorial Sloan-Kettering Cancer Center

Overall Clinical Trial Officials and Contacts

David Amar, MD Principal Investigator Memorial Sloan-Kettering Cancer Center  

Overall Contact: David Amar, MD 212-639-6798 amard@mskcc.org

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00375518

Study ID Number: 06-079

ClinicalTrials.gov Identifier: NCT00375518

Health Authority: United States: Institutional Review Board

Memorial Sloan-Kettering Cancer Center