Thoracic Surgery
Conditions
Keywords
Thoracic Surgery, Cardiopulmonary complications, Atorvastatin
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.
Interventions
DRUGAtorvastatin
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.
DRUGPlacebo
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.
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the Postoperative Complications Found in Each Group | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atorvastatin 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. | 80 |
| Placebo 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. | 82 |
| Total | 162 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Patient Not Treated | 6 | 6 |
| Overall Study | Withdrawal by Subject | 2 | 10 |
Baseline characteristics
| Characteristic | Atorvastatin | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 43 Participants | 36 Participants | 79 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants | 46 Participants | 83 Participants |
| Sex: Female, Male Female | 36 Participants | 33 Participants | 69 Participants |
| Sex: Female, Male Male | 44 Participants | 49 Participants | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 31 / 80 | 33 / 82 |
| serious Total, serious adverse events | 1 / 80 | 1 / 82 |
Outcome results
Primary
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.
Time frame: one week (minimum of 5 days) before surgery and continued for one week (minimum of 5 days) after surgery
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atorvastatin | Determine the Postoperative Complications Found in Each Group | With Post Operative Complications | 16 participants |
| Atorvastatin | Determine the Postoperative Complications Found in Each Group | Without Post Operative Complications | 56 participants |
| Placebo | Determine the Postoperative Complications Found in Each Group | With Post Operative Complications | 8 participants |
| Placebo | Determine the Postoperative Complications Found in Each Group | Without Post Operative Complications | 57 participants |