Clinical trial NCT00534651: Paracetamol and Endothelial Function in Patients With Stable Coronary Artery Disease
Official title: Paracetamol and Endothelial Function in Patients With Stable Coronary Artery Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Arteriosclerosis
Endothelial Function
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2007-09-26
Enrollment: 37
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: 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

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

Eligibility 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

Primary outcomes:
measure: Primary Efficacy endpoint: To investigate the effect of paracetamol on endothelial function as compared to placebo in patients with stable coronary artery disease.
timeFrame: 2 weeks
measure: 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.
timeFrame: 2 Weeks
Secondary outcomes:
measure: To investigate the effect of paracetamol on markers of inflammation and oxidative stress as well as platelet function
timeFrame: two weeks
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital
Study officials:
affiliation: University of Zurich
name: Frank Ruschitzka, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sudano I, Flammer AJ, Periat D, Enseleit F, Hermann M, Wolfrum M, Hirt A, Kaiser P, Hurlimann D, Neidhart M, Gay S, Holzmeister J, Nussberger J, Mocharla P, Landmesser U, Haile SR, Corti R, Vanhoutte PM, Luscher TF, Noll G, Ruschitzka F. Acetaminophen increases blood pressure in patients with coronary artery disease. Circulation. 2010 Nov 2;122(18):1789-96. doi: 10.1161/CIRCULATIONAHA.110.956490. Epub 2010 Oct 18.