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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Thoracic Surgery

Intervention / Treatment
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* Drug: Atorvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Atorvastatin | Drug: Atorvastatin<br>* 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.<br>|
| Placebo Comparator: 2<br>placebo | Drug: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the Postoperative Complications Found in Each Group | 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. | one week (minimum of 5 days) before surgery and continued for one week (minimum of 5 days) after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thoracic Surgery, Cardiopulmonary complications, Atorvastatin