Clinical trial NCT00375518: Study of Atorvastatin Versus Placebo to Reduce Cardiopulmonary Complications After Thoracic Surgery
Official title: Double-Blind Study of Atorvastatin Versus Placebo to Reduce Cardiopulmonary Complications After Thoracic Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Thoracic Surgery
Keywords: Thoracic Surgery
Cardiopulmonary complications
Atorvastatin
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2006-09-13
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Determine the Postoperative Complications Found in Each Group
timeFrame: one week (minimum of 5 days) before surgery and continued for one week (minimum of 5 days) after surgery
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center 1275 York Avenue
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: David Amar, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.