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Prospective Evaluation of Rifalazil Effect On Vascular Symptoms of Intermittent Claudication and Other Endpoints in Chlamydia Seropositive Patients - PROVIDENCE 1
Description:
The goal of the trial was to evaluate treatment with the anti-chlamydial antibiotic rifalazil compared with placebo in patients with intermittent claudication who are highly seropositive for C. pneumonia.
Study Design
Patients Screened: 693
Patients Enrolled: 297
Mean Follow Up: 12 months
Mean Patient Age: Mean age 65 years
Female: 28
Patient Populations:
Age 40-80 years; C. pneumoniae titers (IgG antibody titer ≥1:128); diagnosis of PAD; symptoms of stable intermittent claudication for 6 months; ankle-brachial index ≤0.90 or 20% reduction on treadmill exercise testing; PWT between 1-12 minutes on Gardner treadmill protocol
Primary Endpoints:
Change in peak walking time (PWT) at 6 months
Secondary Endpoints:
Change in PWT (2, 3, 6, 12 months) Change in Claudication Onset Time (2, 3, 6, 12 months) Walking Impairment and SF-36 Questionnaire (3, 6, 12 months)
Drug/Procedures Used:
Patients were randomized to rifalazil (25 mg; n = 153) or placebo (n = 144) given once weekly with treatment to continue for 8 weeks. Patients underwent treadmill testing at baseline and 2, 3, 6, and 12 months.
Principal Findings:
Mean baseline ankle-brachial index was 0.63. Chlamydia titer ≥1:512 was present in 42% of patients. Approximately one-quarter had diabetes.
There was no difference between groups in the primary endpoint of change in peak walking time at 6 months (improvement of 20% in the rifalazil group and 16% in the placebo group, p = NS). There was also no difference in quality of life measurements at 6 months, including the Walking Impairment Questionnaire (mean 35.7 for rifalazil and 39.2 for placebo, p = NS) and the SF 36 Physical Functioning Score (51.5 vs. 51.9, p = NS). Serious adverse cardiovascular events did not differ between groups. There were 3 deaths in the rifalazil group and 1 in the placebo group.
Interpretation:
Among patients with intermittent claudication who are highly seropositive for C. pneumonia, 8-week treatment with the anti-chlamydial antibiotic rifalazil was not associated with a difference in change in peak walking time at 6 months compared with placebo.
Although epidemiological studies suggest C. pneumoniae exacerbates atherosclerosis, prior randomized trials of antibiotic therapy in coronary artery disease patients have shown no benefit, including WIZARD, PROVE-IT, and ACES. However, several small trials of antibiotic therapy in patients with peripheral disease have shown mixed results, with benefit seen mainly in surrogate endpoints such as carotid IMT and walking distance but no benefit observed in clinical events. While C. pneumoniae may be present in the setting of atherosclerosis, it is likely not a cause of atherosclerosis as antibiotic therapy has not been able to modify risk. Very few effective treatment options exist for patients with intermittent claudication.
References:
Jaff MR, Dale RA, Creager MA, et al. Anti-chlamydial antibiotic therapy for symptom improvement in peripheral artery disease: prospective evaluation of rifalazil effect on vascular symptoms of intermittent claudication and other endpoints in Chlamydia pneumoniae seropositive patients (PROVIDENCE-1). Circulation. 2009 Jan 27;119(3):452-8.
Presented by Dr. Michael R. Jaff at the American Heart Association Annual Scientific Session, Orlando, FL, November 2007.
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