Lowering the Risk of Operative Complications Using Atorvastatin Loading Dose (LOAD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Instituto de Ensino e Pesquisa, Hospital do Coracao
ClinicalTrials.gov Identifier:
NCT01543555
First received: February 27, 2012
Last updated: December 30, 2015
Last verified: December 2015
  Purpose
Patients submitted to noncardiac surgeries are at increased risk of serious cardiovascular complications. Statins have shown to lower cholesterol levels and reduce cardiovascular events in other scenarios. The objective of this study is to explore the effects of atorvastatin, as compared with placebo, on the 30-day risk of a composite of death, nonfatal Myocardial Injury after Noncardiac Surgery (MINS), or stroke among patients who undergo noncardiac surgery.

Condition Intervention Phase
Myocardial Infarction
Peripheral Vascular Disease
Aortic Aneurism
Drug: Atorvastatin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Multicenter Randomized Controlled Trial of Loading Dose Statins for the Prevention of Cardiovascular Complications in High-Risk Non-Cardiac Surgery

Resource links provided by NLM:


Further study details as provided by Hospital do Coracao:

Primary Outcome Measures:
  • Composite outcome [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Composite of all-cause mortality, nonfatal myocardial injury after noncardiac surgery and stroke at 30 days.


Secondary Outcome Measures:
  • All-cause mortality [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Death from any cause.

  • Myocardial injury after noncardiac surgery (MINS) [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    An elevated cardiac troponin measurement judged due to cardiac ischemia (i.e., there was no evidence of a non-ischemic etiology like sepsis or pulmonary embolism).

  • Stroke [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    New neurologic symptom with compatible lesion on brain imaging and confirmation by a neurologist of the diagnosis of stroke.

  • Myocardial infarction [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    Rate of myocardial infarction as defined by any 2 of: typical chest pain OR typical ECG changes (ST-segment depression, ST-segment elevation, new Q waves, transitory T wave inversion) OR new rise in troponin levels (CK-MB levels if unavailable) OR new wall motion abnormality on echocardiogram. Pathological confirmation of myocardial necrosis on necropsy will also be accepted

  • Cardiovascular death [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    Evidence of death primarily caused by one of the following: acute myocardial infarction, stroke, pulmonary embolism, heart failure or ventricular arrhythmias.

  • Pulmonary embolism [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Clinical signs accompanied by high-probability ventilation-perfusion lung scan or a filling defect of the pulmonary artery or its branches in a conventional arteriography or multi-slice spiral tomography.

  • Deep venous thrombosis [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Any signs or symptoms of deep vein thrombosis confirmed by adequate images on ultrasound, computed tomography or angiography

  • Clinically relevant atrial fibrillation [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    A newly diagnosed atrial fibrillation that results in angina, heart failure, hypotension, or that requires treatment with an anti-arrhythmic drug or electric cardioversion

  • Rhabdomyolysis [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    elevation of CPK levels higher than 5 times the normal upper limit and myalgia or any CPK elevation higher than 10 times the upper limit, regardless of symptoms.


Enrollment: 648
Study Start Date: November 2012
Study Completion Date: June 2015
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atorvastatin active
Atorvastatin 80mg anytime within 18 hours before surgery. A postoperative 40mg atorvastatin dose administered at least 12 hours after the 80mg loading dose. Subsequently, 40mg atorvastatin daily for the next seven days.
Drug: Atorvastatin
Atorvastatin 80mg anytime within 18 hours before surgery. A postoperative 40mg atorvastatin dose administered at least 12 hours after the 80mg loading dose. Subsequently, 40mg atorvastatin daily for the next seven days.
Other Names:
  • Liptor (R)
  • Kolevas (R)
Placebo Comparator: Placebo
Matching placebo 80mg anytime within 18 hours before surgery. A postoperative 40mg placebo dose administered at least 12 hours after the 80mg loading dose. Subsequently, 40mg placebo daily for the next seven days.
Drug: Placebo
Matching placebo 80mg anytime within 18 hours before surgery. A postoperative 40mg matching placebo dose administered at least 12 hours after the 80mg loading dose. Subsequently, 40mg placebo daily for the next seven days.
Other Name: Standard care

Detailed Description:

Cardiovascular complications, such as myocardial infarction (MI) and stroke are common in the perioperative period of noncardiac surgeries. To the moment there are no safe and effective interventions to reduce vascular events in this scenario. Data from observational studies and small-sized randomized controlled trials (RCTs) have shown promising results in terms of risk reduction. In addition, experimental data have indicated that statins have acute anti-inflammatory properties, which promote the stabilization of atherosclerotic lesions and, therefore, might reduce the risk of MI, even in the short term. This study was designed to explore the effects of atorvastatin, as compared with placebo, on the 30-day risk of a composite of death, nonfatal Myocardial Injury after Noncardiac Surgery (MINS), or stroke among patients who undergo noncardiac surgery.

The study was conducted in accordance with the prespecified protocol and reached successful enrollment rates when, by the end of 2014 the steering committee was invited to join an international initiative and participate in a much larger clinical trial to investigate this relevant question. Due to this outstanding possibility, the steering committee decided to redesign the study which is now formatted as an exploratory trial. As described, the study was completed with the inclusion of 648 participants in June, 2015.

  Eligibility

Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients older than 40 years-old undergoing non-cardiac surgery with an expected hospital stay of at least 24hs and that fulfills any one of the following criteria:

A) Established vascular disease:

i) Major vascular surgery ii) All types of surgery in patients with overt atherosclerosis (any significant or symptomatic coronary, cerebral or peripheral artery disease)

B) Without established vascular disease:

At least 3 risk factors for cardiovascular complications:

  1. Major surgery;
  2. Emergency surgery;
  3. Previous history of heart failure;
  4. diabetes;
  5. Arterial hypertension;
  6. Smoking habit along the last two years;
  7. chronic kidney disease (creatinine greater than 2mg/dl);
  8. Patients older than 70 years.

Exclusion Criteria:

  • Previous intolerance to statins
  • Current rhabdomyolysis
  • Current use of statins
  • Severe Liver Failure (CHILD-PUGH SCORE C)
  • Breast-feeding or pregnancy
  • Low-risk surgeries
  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: NCT01543555

Locations
Brazil
Hospital do Coração
São Paulo, SP, Brazil, 04005-000
Sponsors and Collaborators
Hospital do Coracao
Investigators
Study Chair: Otávio Berwanger, MD, PhD Hospital do Coração
Study Chair: Renato D Lopes, MD Phd Brazilian Clinical Research Institute
  More Information

Publications:

Responsible Party: Instituto de Ensino e Pesquisa, Research Institute HCor, Hospital do Coracao
ClinicalTrials.gov Identifier: NCT01543555     History of Changes
Other Study ID Numbers: 02/15/2012 
Study First Received: February 27, 2012
Last Updated: December 30, 2015
Health Authority: Brazil: Ethics Committee

Keywords provided by Hospital do Coracao:
myocardial infarction
statin
perioperative care
peripheral vascular diseases
anesthesiology

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Aneurysm
Vascular Diseases
Aortic Aneurysm
Peripheral Vascular Diseases
Peripheral Arterial Disease
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Aortic Diseases
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Atorvastatin Calcium
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 28, 2016