The CLARICOR Trial: Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease - Full Text View

Purpose

A growing body of evidence links Chlamydia pneumoniae to the progression of coronary heart disease. The purpose of this study is to determine the positive and negative effect of 14 days treatment with clarithromycin 500 mg daily in patients already suffering from stable coronary heart disease. The participants will be followed for at least two years after the treatment.

Abbott Laboratories supplied Clarithromycin and placebo tablets.

Condition	Intervention	Phase
Heart Disease Cardiovascular Disease	Drug: clarithromycin	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	The Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease - a Randomized, Placebo Controlled, Double Blinded, Multicentre, Clinical Trial

Resource links provided by NLM:

MedlinePlus related topics: Coronary Artery Disease Heart Diseases

Drug Information available for: Clarithromycin

U.S. FDA Resources

Further study details as provided by Copenhagen Trial Unit, Center for Clinical Intervention Research:

Primary Outcome Measures:

Composite consisting of: death regardless of cause
non-fatal AMI or
unstable angina pectoris whichever occurred first

Secondary Outcome Measures:

Composite of: cardiovascular death
non-fatal AMI or
unstable angina pectoris whichever occurred first


Enrollment:	4372
Study Start Date:	October 1999
Study Completion Date:	September 2002
Primary Completion Date:	April 2000 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Clarithromycin Clarithromycin is a lipophilic semi-synthetic macrolide antibiotic. The lipophilic nature of the drug allows it to easily penetrate into body fluids and tissues and accumulate intracellularly. Side effects are few, apart from trivial gastrointestinal complaints, and severe side effects are rarely observed during standard treatment.	Drug: clarithromycin
Placebo Comparator: Placebo Placebo comparator	Drug: clarithromycin

Detailed Description:

Basic science suggests a fundamental role for inflammation in mediating all stages of coronary heart disease (CHD), and a large number of clinical studies have reported an association between markers of inflammation and CHD. Consequently, infectious agents have been proposed as promoters of atherosclerosis and/or acute coronary syndrome (ACS). Many studies have suggested a relation between Chlamydia pneumoniae (C. pneumoniae) infection and CHD, and C. pneumoniae has been demonstrated in atherosclerotic tissue.

Macrolide antibiotics are effective in eradication of C. pneumoniae from atherosclerotic plaques. Two small trials showed significant beneficial effects of macrolides on cardiovascular morbidity in patients with ACS. To corroborate and extend these findings, we undertook a randomised, placebo-controlled trial with clarithromycin in patients with stable CHD in order to test the hypothesis that intervention with a macrolide would reduce cardiovascular risk with regard to mortality and morbidity.

Eligibility


Ages Eligible for Study:	18 Years to 84 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

patients aged 18 to 85 years and
previous acute myocardial infarction (AMI) or
previous or present angina pectoris and
signed informed concent

Exclusion Criteria:

AMI or unstable angina pectoris within the last three months
revascularisation (PTCA or CABG) within the preceding six months
severe heart failure (New York Heart Association (NYHA) functional class IV)
known impaired renal or hepatic function
active malignancy
intolerance to macrolides
treatment with methylxanthines, carbamazepine, cisapride, astemizole, terfenadine, or coumarin anticoagulants
earlier inclusion in the CLARICOR Trial or participation in another drug trial within four weeks
participation in other clinical trials within one month before this trial
individuals incapable of managing own affairs or not able to sign written consent
lack of written consent
women of childbearing age not using reliable contraceptives
breast feeding women

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00121550

Locations


Denmark
Copenhagen Trial Unit, Center for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9
Copenhagen, Denmark, 2100
H:S Rigshospitalet
Copenhagen, Denmark, 2100
H:S Amager Hospital
Copenhagen, Denmark, 2300
H:S Bispebjerg Hospital
Copenhagen, Denmark, 2400
H:S Frederiksberg Hospital
Frederiksberg, Denmark, 2000
H:S Hvidovre Hospital
Hvidovre, Denmark, 2650

Sponsors and Collaborators

Copenhagen Trial Unit, Center for Clinical Intervention Research

Danish Heart Foundation

Copenhagen Hospital Corporation

The Danish Medical Research Council

The 1991 Pharmacy Foundation

Abbott

Investigators


Study Chair:	Christian Jespersen, DMSc	Department of Cardiology Y, Bispebjerg Hospital, Bispebjerg Bakke 23, DK 2400 Copenhagen NV, Denmark.
Principal Investigator:	Christian Gluud, DMSc	Copenhagen Trial Unit, Center of Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen

More Information

Publications:

Jespersen CM, Als-Nielsen B, Damgaard M, Hansen JF, Hansen S, Helø OH, Hildebrandt P, Hilden J, Jensen GB, Kastrup J, Kolmos HJ, Kjøller E, Lind I, Nielsen H, Petersen L, Gluud C; CLARICOR Trial Group. Randomised placebo controlled multicentre trial to assess short term clarithromycin for patients with stable coronary heart disease: CLARICOR trial. BMJ. 2006 Jan 7;332(7532):22-7. Epub 2005 Dec 8. Erratum in: BMJ. 2006 Jan 21;332(7534):151.

Hansen S, Als-Nielsen B, Damgaard M, Helø OH, Petersen L, Jespersen CM. Intervention with clarithromycin in patients with stable coronary heart disease. The CLARICOR Trial Design. Heart Drug 2001;1:14-9.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kjøller E, Hilden J, Winkel P, Galatius S, Frandsen NJ, Jensen GB, Fischer Hansen J, Kastrup J, Jespersen CM, Hildebrandt P, Kolmos HJ, Gluud C; CLARICOR Trial Group. Agreement between public register and adjudication committee outcome in a cardiovascular randomized clinical trial. Am Heart J. 2014 Aug;168(2):197-204.e1-4. doi: 10.1016/j.ahj.2013.12.032. Epub 2014 May 4.

Lyngbæk S, Winkel P, Gøtze JP, Kastrup J, Gluud C, Kolmos HJ, Kjøller E, Jensen GB, Hansen JF, Hildebrandt P, Hilden J; CLARICOR Trial Group. Risk stratification in stable coronary artery disease is possible at cardiac troponin levels below conventional detection and is improved by use of N-terminal pro-B-type natriuretic peptide. Eur J Prev Cardiol. 2014 Oct;21(10):1275-84. doi: 10.1177/2047487313492099. Epub 2013 May 30.

Winkel P, Hilden J, Fischer Hansen J, Hildebrandt P, Kastrup J, Kolmos HJ, Kjøller E, Jespersen CM, Gluud C, Jensen GB; CLARICOR Trial Group. Excess sudden cardiac deaths after short-term clarithromycin administration in the CLARICOR trial: why is this so, and why are statins protective? Cardiology. 2011;118(1):63-7. doi: 10.1159/000324533. Epub 2011 Mar 26.

Harutyunyan MJ, Mathiasen AB, Winkel P, Gøtze JP, Hansen JF, Hildebrandt P, Jensen GB, Hilden J, Jespersen CM, Kjøller E, Kolmos HJ, Gluud C, Kastrup J; CLARICOR Trial Group. High-sensitivity C-reactive protein and N-terminal pro-B-type natriuretic peptide in patients with stable coronary artery disease: a prognostic study within the CLARICOR trial. Scand J Clin Lab Invest. 2011 Feb;71(1):52-62. doi: 10.3109/00365513.2010.538081. Epub 2010 Nov 25.

Jensen GB, Hilden J, Als-Nielsen B, Damgaard M, Hansen JF, Hansen S, Helø OH, Hildebrandt P, Kastrup J, Kolmos HJ, Kjøller E, Lind I, Nielsen H, Petersen L, Jespersen CM, Gluud C; CLARICOR Trial Group. Statin treatment prevents increased cardiovascular and all-cause mortality associated with clarithromycin in patients with stable coronary heart disease. J Cardiovasc Pharmacol. 2010 Feb;55(2):123-8. doi: 10.1097/FJC.0b013e3181c87e37.

Jespersen CM, Kolmos HJ, Frydendall N, Hilden J, Gluud C, Hansen JF; CLARICOR Trial Group. Compliance with and short-term adverse events from clarithromycin versus placebo in patients with stable coronary heart disease: the CLARICOR trial. J Antimicrob Chemother. 2009 Aug;64(2):411-5. doi: 10.1093/jac/dkp190. Epub 2009 May 28.


Responsible Party:	Christian Gluud, MD, DMSc, Copenhagen Trial Unit, Center for Clinical Intervention Research
ClinicalTrials.gov Identifier:	NCT00121550 History of Changes
Other Study ID Numbers:	1997-08-DP-42-RKF-13 CLARICOR; REC: KF01-076/99 DDPA: 2001-41-1496, DMA: 2612-975
Study First Received:	July 13, 2005
Last Updated:	August 10, 2016
Health Authority:	Denmark: Danish Medicines Agency Denmark: The Regional Committee on Biomedical Research Ethics

Keywords provided by Copenhagen Trial Unit, Center for Clinical Intervention Research:


Coronary heart disease Clarithromycin Macrolides Cardiovascular mortality Chlamydia pneumoniae

Additional relevant MeSH terms:


Cardiovascular Diseases Heart Diseases Myocardial Ischemia Coronary Artery Disease Vascular Diseases Coronary Disease Arteriosclerosis Arterial Occlusive Diseases	Clarithromycin Anti-Bacterial Agents Anti-Infective Agents Protein Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 26, 2016