PROVIDENCE-1 trial Results: Rifalazil Has No Effect in Patients with Intermittent Claudication

November 7, 2007 By Katherine Ogando [mailto:kogando@perfuse.org]

Orlando, FL: The anti-chlamydial antibiotic rifalazil is not linked to an increase in peak walking time (PWT) among patients with peripheral arterial disease (PAD), according to data presented at the American Heart Association Scientific Sessions 2007 from the PROVIDENCE-1 (Prospective Evaluation of Rifalazil Effect on Vascular Symptoms of Intermittent Claudication and Other Endpoints in Chlamydia Seropositive Patients-1) trial.

Prior research indicates that patients who are seropositive for C. pneumonia are at an increased risk of aggravation of PAD symptoms. The antibiotic rifalazil has proven to be an effective treatment of C. pneumonia, and the authors hypothesized that the use of rifalazil would improve the PWT of patients with intermittent claudication.

PROVIDENCE-1 is a randomized, blinded, multinational, multicenter, prospective trial. The trial included 297 patients between 40-80 years of age, and had a mean follow-up of 12 months. Enrolled patients had a diagnosis of PAD, C. pneumonia titers (IgG antibody titer > 1:128), symptoms of intermittent claudication for 6 months, and an ankle-brachial index less than or equal to 0.90, in addition to PWT between 1 to 12 minutes on Gardner treadmill protocol. 153 patients were randomized to 25 mg of rifalazil and 144 patients to placebo, administered on a weekly basis for 8 weeks.

The primary endpoint of the study was a change in PWT among the patients 6 months after baseline. Secondary endpoints included a change in PWT at 2, 3, 6, and 12 months; change in claudication onset time measured at 2, 3, 6, and 12 months; and responses on the Walking Impairment and SF-36 Physical Functioning Questionnaire at 3, 6, and 12 months. The results demonstrated a 20% change in the rifalazil group vs. a 16% change in placebo (p=NS), indicating that the use of rifalazil is not associated with improved PWT among patients with PAD. In addition, there was no significant difference between the groups in the quality of life assessments. For the Walking Impairment Questionnaire, the rifalazil group scored 35.7 (p=NS) and placebo scored 39.2 (p=NS) at 6 months. Similarly for the SF-36 Questionnaire, the experimental group scored 51.5 vs. 51.9 in placebo (p=NS).

According to the results of PROVIDENCE-1, a treatment of rifalazil, compared to placebo, is not associated with a change in PWT, or any benefit to patients with intermittent claudication, after 6 months. Further trials are needed to explore other potentially effective treatment options for patients with intermittent claudication.

PROVIDENCE-1 was sponsored by ActivBiotics, Inc.

References

1. Presented by Dr. Michael R. Jaff at the American Heart Association Annual Scientific Session, Orlando, FL, November 2007.