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Zavicefta noninferior to meropenem in treatment of patients with HAP
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Phase 3 results from the REPROVE trial demonstrated the noninferiority of Zavicefta to meropenem for treatment of patients with hospital-acquired pneumonia, including ventilator-associated pneumonia, according to researchers.
In the trial, patients with hospital-acquired pneumonia (HAP) who were treated with Zavicefta (ceftazidime/avibactam, Pfizer) — known as Avycaz (Allergan) in the U.S. — experienced statistically equivalent rates of clinical cure compared with patients who received meropenem, a broad-spectrum carbapenem antibiotic that is considered the standard of care.
According to Antoni Torres, MD, PhD, pulmonologist at the Hospital Clinic of Barcelona and professor at the University of Barcelona, it was the first trial to show the noninferiority of ceftazidime/avibactam to meropenem in patients with HAP.
“This is important because there is a concern over the resistance of carbapenems to gram-negative bacilli and we want to spare carbapenems, so now we have another drug that can be used instead of meropenem,” Torres told Infectious Disease News in a telephone interview from Vienna, Austria, where the results of the study were presented at the European Congress of Clinical Microbiology and Infectious Diseases.
Ceftazidime-avibactam is approved in the U.S. for the treatment of complicated intra-abdominal infections and complicated urinary tract infections, but not HAP. It has been approved in Europe for patients with HAP since June 2016.
The REPROVE trial took place in 23 countries between April 2013 and December 2015. Torres and colleagues randomly assigned adults aged 18 to 90 years to receive 2-hour IV infusions of ceftazidime/avibactam (2,000 mg/500 mg) or 30-minute IV infusions of meropenem (1,000 mg) every 8 hours for up to 2 weeks, with doses adjusted for renal function. Approximately 13.2% of the 808 patients included in the study had an APACHE score of 20 or greater, and 34.7% had ventilator-associated pneumonia (VAP), according to Torres and colleagues.
Among 405 patients who received ceftazidime/avibactam treatment, the clinical cure rates in the clinically modified intent-to-treat (cMITT) population and clinically evaluable (CE) population were 68.8% and 77.4%, respectively, after 21 to 25 days, compared with 73.0% and 78.1% among 403 patients in the meropenem treatment arm. Torres and colleagues said subgroup analyses of patients with and without VAP were consistent with the primary analysis.
The adverse event rate for patients treated with ceftazidime/avibactam was 74.6% compared with 74.2% for meropenem and the serious adverse event rates were 18.5% and 13.4%, respectively, with the most frequent adverse event in both arms being diarrhea. Further, the all-cause mortality rate at Day 28 after randomization was also similar in the two groups.
Torres said the results mean physicians have more options to effectively treat patients with HAP. – by Gerard Gallagher
Reference: Torres A, et al. Abstract #OS0603. Presented at: 27th European Congress of Clinical Microbiology and Infectious Diseases; April 22-25; Vienna, Austria.
Disclosures: Torres reports being an employee of the Hospital Clinic of Barcelona, which received institutional research grant funding from AstraZeneca for the study.