- A 112-patient that the FDA accepted as the first of the two supportive trials needed for approval.
- A with 196 patients that tested terlipressin plus albumin against placebo plus albumin and showed a nominal benefit from terlipressin that failed to achieve statistical significance.
- The most recent trial, , which directly led to the advisory committee session. That trial enrolled 300 patients and met its primary endpoint. Data have not yet been published but have been at meetings.
One of the sources of controversy over the benefit from terlipressin centered on the primary endpoint used in CONFIRM, which required that the patient have two consecutive, low readings for serum creatinine, with levels no greater than 1.5 mg/dL while on treatment, and remain alive and free from need for renal replacement therapy for at least 10 days beyond this.
The FDA agreed to accept this as a primary endpoint but nonetheless considered it a surrogate.
According to FDA staffers who presented their take on the application, the agency accepted this primary endpoint “with the understanding that favorable trends in clinical outcomes, thought to be predicted by successful treatment of hepatic renal syndrome type 1, would be expected.”
The lack of many favorable trends in clinical outcomes helped foster the advisory committee’s divided response. The FDA’s staff uses its discretion when considering an advisory committee’s recommendations and making a final determination.
None of the advisory committee members disclosed any relevant financial relationships.
A version of this article originally appeared on Medscape.com.