Effect of 8 weeks oral Pentaerithrityltetranitrate on endothelial dysfunction in patients with coronary artery disease: A prospective, randomized, double-blind, placebo-controlled, monocentric clinical trial of phase IV - PENTA

• Conditions: Women or men >35 and < 80 years of age with documented, clinically stable coronary artery disease with stable angina pectoris from the heart catheter register, II. Med. Klinik, Johannes Gutenberg-University Mainz.; MedDRA version: 9.1Level: LLTClassification code 10049194Term: Stable angina pectoris; MedDRA version: 9.1Level: LLTClassification code 10011093Term: Coronary atherosclerosis

• Registration Number: EUCTR2006-004533-15-DE
• Lead Sponsor: Johannes Gutenberg-Universität Mainz, II. Med. Klinik (ausführende Stelle), Prof. Dr. T. Münzel

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-08-13
• Last Update Posted: 1 May 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

Subjects meeting all of the following criteria will be considered for admission to the trial:
-Men or women > 35 and < 80 years of age
-Documented clinically stable CAD with stable angina pectoris
-Ability of subject to understand the character and individual consequences of the clinical trial
-Written informed consent must be available before enrollment in the trial
-For women with childbearing potential, adequate contraception (oral contraceptives or intrauterine devices) is required.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects presenting with any of the following criteria will not be included in the trial:
-Clinical signs of congestive heart failure or left ventricular ejection fraction <30% (as demonstrated within the last 1 year by echocardiography, LV an-giography, MRI or radionuclide ventriculography, respectively)
-Uncontrolled hypertension (blood pressure >180/110mmHg) or hypotension (systolic blood pressure <110 mmHg)
-Initiation of any of the following medications within the last 8 weeks: Aspirin, statins, calcium antagonists, ACE-inhibitors or AT1 receptor blockers, hor-mone replacement therapy. Individuals who take any of these drugs longer than 8 weeks can be included in this trial.
-Use of Phosphodiesterase-5-inhibitors (Viagra®, Revatio®, Cialis®, Levitra®), dihydroergotamine and nitrates i.e. isosorbidemononitrate, isosorbidedinitrate, nitroglycerin, pentaerithrityltetranitrate or molsidomin within the last two weeks.
-Hemodynamically significant aortic or mitral stenosis or hypertrophic obstructive cardiomyopathy (as demonstrated within the last year by echocardiogra-phy, invasive right/ left heart catheterization or MRI, respectively)
-Renal dysfunction (plasma creatinine (men: > 2.0 mg/dl, women: : > 1.8 mg/dl))
-Known hepatic disease or elevation of serum transaminases or gGT > 3x ULN (upper limit of normal range)
-WBC >16.000 or platelet count >500.000/µl or <75.000/µl
-Clinically overt hyperthyreodism
-Pregnancy and lactation
-Known intolerance to organic nitrates
-History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharma-ceutical form of the investigational medicinal product
-Other significant laboratory abnormalities that the investigator feels may com-promise the patient’s safety by participation in the study
-Participation in other clinical trials and observation period of competing trials, respectively

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The main objective is to evaluate the effect of an 8 weeks oral pentaerithrityltetranitrate therapy in addition to standard long-term CAD medication on flow dependent vasodilation (FMD) in patients suffering from coronary artery disease.<br>;Secondary Objective: Secondary objectives of the trial include the effects of pentaerithrityltetranitrate therapy on bilirubin, ferritin, hs-CRP plasma concentration, mitochondrial ALDH-2 activity, ENDOPAT 2000 index as well as endothelium-independent nitrogylcerin-induced vasodilation (NMD).<br>;Primary end point(s): The primary endpoint variable is the absolute change in FMD from baseline to 8 weeks-follow-up. It is formed as FMD at follow-up (V3) – FMD at baseline (V0). FMD is measured in %.