Paracetamol and Endothelial Function in Patients With Stable Coronary Artery Disease

Condition(s) targeted: Coronary Arteriosclerosis; Endothelial Function

Intervention: Paracetamol (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: University of Zurich

Official(s) and/or principal investigator(s):
Frank Ruschitzka, MD, Principal Investigator, Affiliation: University of Zurich

Overall contact:
Rosy Hug, Phone: +41 44 255 93 20, Email: rosy.hug@usz.ch

The purpose of this study is to determine the effect of orally given paracetamol on the vascular function and on 24-hour blood pressure in patients with coronary artery disease

Official title: Paracetamol and Endothelial Function in Patients With Stable Coronary Artery Disease

Study design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Safety/Efficacy Study

Primary outcome:

Primary Efficacy endpoint: To investigate the effect of paracetamol on endothelial function as compared to placebo in patients with stable coronary artery disease.

primary safety endpoint: to evaluate the effect of paracetamol on 24-hour systolic and diastolic blood pressure as compared to placebo in patients with stable coronary artery disease.

Secondary outcome: To investigate the effect of paracetamol on markers of inflammation and oxidative stress as well as platelet function

Detailed description: Patients with chronic pain diseases (e. g. osteoarthritis) are dependent on effective medication. NSAIDs are very effective in lowering pain in these patients. Recently there has aroused major concern with regard to cardiovascular side effects and safety, especially in selective cyclooxygenase-2 inhibitors (coxibs) but also in "regular" NSAIDs.

At the moment, there is a big confusion, whether these drugs still should be used, especially in patients with known coronary artery disease. Physicians now try to switch to high dose paracetamol, despite the weaker efficacy in pain relieve, because this drug is considered generally as not harmful.

As there is very few information on the cardiovascular effect of this drug, we plan to perform this study and investigate the impact of paracetamol on endothelial function, an important cardiovascular surrogate marker, on inflammatory markers and on oxidative stress in patients with coronary artery disease on top of standard medication, including aspirin

Minimum age: 30 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Age: 30 - 80 years

- History of coronary artery disease (documented by coronary angiogram, nuclear

imaging, positive stress test)

- Stable cardiovascular medication for at least 1 month

- Written obtained informed consent

Exclusion Criteria:- myocardial infarction, unstable angina, stroke within 3 months prior to study entry

- coronary intervention/revascularisation procedure within 3 months prior to study

entry

- Left ventricular ejection fraction <50%

- Other analgesics (Platelet inhibition therapy with Aspirin 100mg/d will be continued)

- Long acting nitrates

- Smoking

- Chronic heart failure (> NYHA II)

- Ventricular tachyarrhythmias

- Renal failure (serum creatinine >200umol)

- Liver disease (ALT or AST >100 IU), especially acute hepatitis

- Hyperbilirubinemia

- Alcohol abuse

- Oral Anticoagulation

- Concomitant therapy with Phenobarbital, Phenytoin, Carbamazepin, Isonicotinic Acid,

Chloramphenicol Chlorzoxazone, Zidovudine, Salicylamide

- Insulin-dependent diabetes mellitus

- Drug abuse

- Anemia (Hb<10 g/dl)

- Known allergies on Paracetamol

- Pregnancy

- Malignancy (unless healed or remission > 5 years)

- Symptomatic hypotension, hypertension >160/100 mmHg

- Disease with systemic inflammation (e. g. rheumatoid arthritis, M. Crohn)

- Participation in another study within the last month

Rosy Hug, Phone: +41 44 255 93 20, Email: rosy.hug@usz.ch

University Hospital, zurich 8091, Switzerland; Recruiting

Starting date: November 2006
Ending date: December 2010
Last updated: June 2, 2009