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

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00375518
• Collaborator: (none)
• Enrollment: 162
• Location: 1
• Arms: 2
• Duration (Months): 94
• Patients Per Site Per Month: 1.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Thoracic Surgery	Drug: Atorvastatin; Drug: Placebo	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 162 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Double-Blind Study of Atorvastatin Versus Placebo to Reduce Cardiopulmonary Complications After Thoracic Surgery
• Study Start Date: Jul 1, 2006
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Memorial Sloan-Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00375518
• Other Study ID Numbers: 06-079
• First Posted: Sep 13, 2006
• Last Update Posted: Jan 6, 2021
• Last Verified: Dec 1, 2020

• Keywords provided by Memorial Sloan Kettering Cancer Center: Thoracic Surgery; Cardiopulmonary complications; Atorvastatin
• Additional relevant MeSH terms: Aneurysm, Dissecting; Atorvastatin

Study Results

Participant Flow

Arm/Group Title	Atorvastatin	Placebo
Arm/Group Description	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: 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.
Period Title: Overall Study
STARTED	80	82
COMPLETED	72	65
NOT COMPLETED	8	17

Baseline Characteristics

Arm/Group Title	Atorvastatin	Placebo	Total
Arm/Group Description	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: 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.	Total of all reporting groups
Overall Participants	80	82	162
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	37 46.3%	46 56.1%	83 51.2%
>=65 years	43 53.8%	36 43.9%	79 48.8%
Sex: Female, Male (Count of Participants)
Female	36 45%	33 40.2%	69 42.6%
Male	44 55%	49 59.8%	93 57.4%

Outcome Measures

1. Primary Outcome

Title	Determine the Postoperative Complications Found in Each Group
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Atorvastatin	Placebo
Arm/Group Description	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: 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.
Measure Participants	72	65
With Post Operative Complications	16 20%	8 9.8%
Without Post Operative Complications	56 70%	57 69.5%

Adverse Events

Arm/Group Title	Atorvastatin		Placebo
Arm/Group Description	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: 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.
All Cause Mortality
	Atorvastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Atorvastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/80 (1.3%)		1/82 (1.2%)
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Synd (ARDS)	1/80 (1.3%)	1	1/82 (1.2%)	1
Other (Not Including Serious) Adverse Events
	Atorvastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/80 (38.8%)		33/82 (40.2%)
Blood and lymphatic system disorders
Hemoglobin	5/80 (6.3%)	5	6/82 (7.3%)	6
Lymphopenia	15/80 (18.8%)	15	17/82 (20.7%)	17
Metabolism and nutrition disorders
Glucose, high (hyperglycemia)	7/80 (8.8%)	7	5/82 (6.1%)	5
Phosphate, low (hypophosphatemia)	12/80 (15%)	12	20/82 (24.4%)	20
Sodium, low (hyponatremia)	5/80 (6.3%)	5	0/82 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.