Phase 3
Completed N=251
Targeting Inflammation Using Salsalate in CardioVascular Disease
Source: ClinicalTrials.gov NCT00624923 ↗Enrolled (actual)
251
Serious AEs
25.9%
Results posted
Dec 2017
Primary outcomePrimary: Change in Non-calcified Plaque Volume in the Coronary Arteries Assessed by MDCTA From Baseline to 30 Months — 0; 0 mm^3
◆ Published Evidence
Established
61citations · ~6 / year
Effect of Targeting Inflammation With Salsalate: The TINSAL-CVD Randomized Clinical Trial on Progression of Coronary Plaque in Overweight and Obese Patients Using Statins.
Summary
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.
Linked Publications (2)
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Effect of Targeting Inflammation With Salsalate: The TINSAL-CVD Randomized Clinical Trial on Progression of Coronary Plaque in Overweight and Obese Patients Using Statins.
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Salsalate reduces atherosclerosis through AMPKβ1 in mice.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Non-calcified Plaque Volume in the Coronary Arteries Assessed by MDCTA From Baseline to 30 Months |
0; 0 | — |
| SECONDARY Change in Cholesterol |
5.1; 2.0 | — |
| SECONDARY Change in Inflammation Marker: CRP |
-0.1; -0.1 | — |
| SECONDARY Change in Inflammation in the Liver Associated With Nonalcoholic Steatohepatitis (NASH), ALT |
-1.1; -0.6 | — |
Eligibility Criteria
Inclusion Criteria
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) 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 probeneci
Data sourced from ClinicalTrials.gov (NCT00624923) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.