FDA: Doribax trial halted for increase in death rate, poor clinical cure rate

FDA recently announced that a clinical trial evaluating the effects of doripenem (Doribax, Janssen) on the treatment of patients with ventilator-associated pneumonia was halted because of an increase in death rate and a poor clinical cure rate.

The prospective, randomized, double-blind, double-dummy, multicenter phase 3 study was designed to evaluate treatment with doripenem to imipenem-cilastatin. However, the interim analyses were demonstrating a numerically higher mortality rate and a numerically lower clinical cure rate among patients treated with a fixed 7-day course of doripenem (1 g, 4-hour infusion, q8h) compared with those treated with a fixed 10-day course of imipenem-cilastatin (1g, 1 hour infusion, q8h).

Interim results for 274 of the planned 524 patients showed that patients receiving doripenem had a 28-day, all-cause mortality rate of 21.5% compared with the 14.8% in patients receiving imipenem-cilastatin (Primaxin, Merck). In addition, patients in the treatment group had an 11.2% lower rate of being cured compared with patients in the control group.

Doripenem is approved for the treatment of complicated intra-abdominal infections and complicated urinary tract infections including pyelonephritis in adults.

“Doribax is still considered safe and effective for its approved indications,” FDA stated. However, healthcare professionals should know that doripenem is not approved to treat any type of pneumonia, and the recommended dose is 500 mg every 8 hours intravenously, given over 1 hour, for a total of 5 to 14 days (depending on indication) in adults. 

Janssen said that it is committed to ensuring the drug is used safely and effectively and advises healthcare professionals to report any serious adverse events suspected to be associated with the use of doripenem to Janssen at (800) 526-7736. The company also recommends that serious adverse event information be reported directly to FDA’s MedWatch reporting system.