JAC Advance Access published online on May 28, 2009
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkp190
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Original research |
Compliance with and short-term adverse events from clarithromycin versus placebo in patients with stable coronary heart disease: the CLARICOR trial
1 The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark 2 Department of Cardiology Y, Bispebjerg Hospital, Copenhagen University Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen, Denmark 3 Department of Clinical Microbiology, Odense University Hospital, Sdr. Boulevard 29, DK-5000 Odense, Denmark 4 Department of Biostatistics, Institute of Public Health, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark
Received 3 February 2009; returned 25 February 2009; revised 27 April 2009; accepted 28 April 2009
* Corresponding author. Tel: +4535-45-71-75; E-mail: cgluud{at}ctu.rh.dk
Background: The randomized placebo-controlled double-blind CLARICOR trial investigated the influence of clarithromycin versus placebo on cardiovascular events and mortality in patients with chronic coronary artery disease (ClinicalTrials.gov NCT 00121550). The trial randomized 2172 patients to 500 mg of clarithromycin daily versus 2200 patients to matching placebo for 14 days. This paper presents protocol-specified analysis of the patient-reported information regarding their compliance and non-serious adverse events during the 14 days of treatment as well as serious adverse events (mortality and hospitalizations) during the first 30 days after randomization.
Methods: Randomized clinical trial focusing on patient-reported information regarding their compliance and adverse events.
Results: Of the randomized patients, 99% reported information regarding their compliance and adverse events. A 100% tablet intake was reported by 90% of the clarithromycin group and by 93.7% of the placebo group. Of the clarithromycin patients, 39.5% reported at least one non-serious adverse event versus 25.1% of the placebo patients (P < 0.001). Gastrointestinal adverse reactions were reported 950 times by 697 patients (32.3%) in the clarithromycin group and 485 times by 390 patients (17.9%) in the placebo group (P < 0.001). No significant differences were seen in other non-serious or serious adverse events during the first month after inclusion. Short-term non-serious adverse events did not explain the previously reported long-term significantly increased mortality associated with clarithromycin.
Conclusions: Gastrointestinal adverse reactions are common during clarithromycin administration, but at least half are also seen with a placebo.
Key Words: adverse reactions , macrolides , morbidity , mortality
Contributors are listed in the Acknowledgements section.