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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00375518
First received: September 11, 2006
Last updated: May 29, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention
Thoracic Surgery
Drug: Atorvastatin
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Double-Blind Study of Atorvastatin Versus Placebo to Reduce Cardiopulmonary Complications After Thoracic Surgery

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome 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 ] [ Designated as safety issue: Yes ]

Enrollment: 162
Study Start Date: July 2006
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Atorvastatin
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.
Placebo Comparator: 2
placebo
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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00375518

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center 1275 York Avenue
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: David Amar, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00375518     History of Changes
Other Study ID Numbers: 06-079
Study First Received: September 11, 2006
Last Updated: May 29, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Thoracic Surgery
Cardiopulmonary complications
Atorvastatin

Additional relevant MeSH terms:
Atorvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 19, 2014