Targeting Inflammation Using Salsalate in CardioVascular Disease (TINSAL-CVD)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 340
- 试验地点
- 5
- 主要终点
- Change in Non-calcified Plaque Volume in the Coronary Arteries Assessed by MDCTA From Baseline to 30 Months
研究概览
简要总结
The hypothesis is that western lifestyle, with sedentary behaviors and caloric excess promote a chronic, subacute inflammatory state that participates in the development and progression of atherosclerosis. We will evaluate the effects of targeting inflammation using the anti-inflammatory drug salsalate, compared to placebo, on coronary artery plaque volume assessed by multi-detector computed tomographic angiography (MDCTA). The TINSAL-CVD study is a randomized, double-masked, placebo-controlled, 2 arm, clinical trial.
The purpose of the study is to compare the effect of salsalate or placebo on sub-acute inflammation and coronary plaque, in people with cardiovascular disease. Participants are randomized to active intervention (salsalate) or placebo interventions for a period of 30 months. The primary endpoint is change in plaque volume in the coronary arteries assessed by MDCTA from baseline to 30 months.
详细描述
OBJECTIVE:
To determine whether targeting inflammation using salsalate compared with placebo reduces progression of noncalcified coronary artery plaque.
DESIGN, SETTING, AND PARTICIPANTS:
In the Targeting Inflammation Using Salsalate in Cardiovascular Disease (TINSAL-CVD) trial participants were randomly assigned to 30 months of salsalate or placebo in addition to standard, guideline-based therapies. Randomization was computerized and centrally allocated, with patients, health care professionals, and researchers masked to treatment assignment. Participants were overweight and obese statin-using patients with established, stable coronary heart disease.
INTERVENTIONS:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eligibility will be based upon the presence of established coronary artery disease including
- •previous myocardial infarction (≥6 months ago), or
- •previous coronary bypass surgery (> 12 months ago), or
- •stable angina, or
- •significant non-calcified plaque in at least one coronary artery, or
- •abnormal exercise tolerance test or
- •an area of reversible ischemia on nuclear imaging study or pharmacologic stress, with subsequent revascularization, or angioplasty, or
- •abnormal exercise treadmill stress test with or without nuclear imaging or echocardiography with the following exclusions:
- •Exclusions based on nuclear imaging:
- •Transient cavity dilation
- •More than one vascular territory involved with reversible defect (multiple defects)
- •Reversible defects involving the anterior wall, septum or apex (LAD territory)
- •Exclusions based on echocardiography imaging:
- •More than one vascular territory involved with inducible wall motion abnormalities (multiple defects)
- •Inducible wall motion abnormalities involving the anterior wall, septum or apex (LAD territory)
- •Subjects should be at list 6 months after a myocardial infarction and/or revascularization procedure to be eligible.
- •In addition, subjects must be:
- •aged 21- 75 years inclusive,
- •BMI ≥ 27 kg/m2 and ≤ 35 kg/m2 if female and ≤ 40 kg/m2 if male (a BMI ≥24.5 for subjects from Asian origin)
- •on a stable dose of an HMG CoA reductase inhibitor (statin) for 1 month at screening or unable to tolerate a statin,
- •have normal renal function, (note estimated creatinine clearance calculated using Cockcroft-Gault (CG) equation ≥60 at screening [eCrCLCG (ml/min) = [(140 - age) x weight (kg)]/[SCr(mg/dl) x 72] x [0.85 if female],
- •have liver function (ALT, AST) < 3 times upper limits of normal),
- •normal thyroid function (on stable dose replacement therapy is acceptable),
- •if women are of child bearing potential they must have a pregnancy test prior to the CT angio and use contraception for the remainder of the study
- •patients with T2D must have a fasting glucose of ≤ 200 mg/dl at screening and cannot be treated with thiazolidinedione class agents or insulin or Extendin-4 (Byetta) therapy.
- •Subjects must be willing to have at least three visits at the Beth Israel-Deaconess Medical Center/Joslin Diabetes Center with a baseline and a 30-month follow-up series of imaging studies including CT angiography of the coronary arteries and imaging of the aorta, abdominal adiposity and liver, and interim visit at 1 year.
排除标准
- •Unstable angina (increase in frequency or severity of anginal episodes or development of chest pain at rest)
- •significant obstructive disease (≥ 70%) in left main coronary artery, ostial LAD or three-vessel disease by MDCTA
- •Significant heart failure (NYHA class III and IV)
- •Current atrial fibrillation or Wolf-Parkinson-White (WPW) syndrome
- •Allergy to beta-blocker in subjects with resting heart rate > 65 bpm
- •Systolic blood pressure > 160 mm Hg
- •Diastolic BP > 100 mm Hg
- •Persons with allergies to contrast material
- •History of asthma if unable to tolerate beta blocker
- •Allergy to iodinated contrast material or shellfish
- •Allergy to nitroglycerin
- •BMI > 35 kg/m2 if female and > 40 kg/m2 if male
- •Body weight > 350 lbs
- •Use of drugs for weight loss [e.g. Xenical (orlistat), Meridia (sibutramine), Acutrim (phenylpropanolamine) or similar over-the counter medications] within three months of screening
- •Surgery within 30 days of screening
- •History of acquired immune deficiency syndrome or human immunodeficiency virus (HIV)
- •Poor mental function or history of dementia/ Alzheimer's Disease or on medications used for treatment of dementia [e.g. Tacrine (Cognex), Rivastigmine (Exelon), Galantamine (Razadyne, Reminyl), Donepezil (Aricept), Memantine (Namenda)] or any other reason to expect patient difficulty in complying with the requirements of the study
- •Medicine for erectile dysfunction within 72 hours prior to MDCTA
- •History of significant chronic rheumatologic or other chronic inflammatory disease (including foot ulcers)
- •Prior hemorrhagic stroke
- •persons with known aspirin allergy
- •Use of continuous oral corticosteroid treatment (more than 2 weeks), or patients requiring corticosteroids within 3 months
- •Anti-diabetic medication including thiazolidinedione (pioglitazone or rosiglitazone), or insulin or Extendin-4 (Byetta)
- •History of peptic ulcer or gastritis within 5 years
- •Positive stool guaiac
- •Hemoglobin 2 standard deviations below normal
- •Low platelet count (2 standard deviations below normal)
- •Known bleeding disorder
- •Coumadin (warfarin compounds)
- •History of type 1 diabetes and/or history of ketoacidosis
- •Daily use of NSAIDS (including salsalate) for arthritis
- •History of malignancy, except subjects who have been disease-free for greater than 5 years, or whose only malignancy has been basal or squamous cell skin carcinoma
- •History of drug or alcohol abuse, or current weekly alcohol consumption >14 units/week (1 unit = 1 beer, 1 glass of wine, 1 mixed cocktail containing 1 ounce of alcohol)
- •Use of probenecid (Benemid, Probalan), sulfinpyrazone (Anturane) or other uricosuric agents
- •Chronic tinnitus.
研究组 & 干预措施
1- Active Pharmacologic
Salsalate
干预措施: Salsalate (Drug)
2- Placebo
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Non-calcified Plaque Volume in the Coronary Arteries Assessed by MDCTA From Baseline to 30 Months
时间窗: Baseline to 30 months
次要结局
- Change in Cholesterol(Baseline to 30 mo)
- Change in Inflammation Marker: CRP(baseline to 30 mo)
- Change in Inflammation in the Liver Associated With Nonalcoholic Steatohepatitis (NASH), ALT(baseline to 30 mo)