A Phase 3, Randomized, Placebo-Controlled Evaluation of the Safety of Intravenous Meloxicam Following Major Surgery

Sergio D Bergese, Timothy I Melson, Keith A Candiotti, Sabry S Ayad, Randall J Mack, Stewart W McCallum, Wei Du, Alexis Gomez, Jorge E Marcet, Sergio D Bergese, Timothy I Melson, Keith A Candiotti, Sabry S Ayad, Randall J Mack, Stewart W McCallum, Wei Du, Alexis Gomez, Jorge E Marcet

Abstract

An intravenous (IV) formulation of meloxicam is being studied for moderate to severe pain management. This phase 3, randomized, multicenter, double-blind, placebo-controlled trial evaluated the safety of once-daily meloxicam IV 30 mg in subjects following major elective surgery. Eligible subjects were randomized (3:1) to receive meloxicam IV 30 mg or placebo administered once daily. Safety was evaluated via adverse events, clinical laboratory tests, vital signs, wound healing, and opioid consumption. The incidence of adverse events was similar between meloxicam IV- and placebo-treated subjects (63.0% versus 65.0%). Investigators assessed most adverse events as mild or moderate in intensity and unrelated to treatment. Adverse events of interest (injection-site reactions, bleeding, cardiovascular, hepatic, renal, thrombotic, and wound-healing events) were similar between groups. Over the treatment period, meloxicam IV was associated with a 23.6% (P = .0531) reduction in total opioid use (9.2 mg morphine equivalent) compared to placebo-treated subjects. The results suggest that meloxicam IV had a safety profile similar to that of placebo with respect to numbers and frequencies of adverse events and reduced opioid consumption in subjects with moderate to severe postoperative pain following major elective surgery.

Trial registration: ClinicalTrials.gov NCT02720692.

Keywords: meloxicam; nonsteroidal anti-inflammatory drug; postoperative pain; safety; surgery.

Conflict of interest statement

Sergio D. Bergese has received grants from Recro Pharma, Inc. Keith A. Candiotti has received consultancies and grants from Recro Pharma, Inc. Randall J. Mack and Stewart W. McCallum have stock ownership and options and are employees of Recro Pharma, Inc. Wei Du receives consultancies from Recro Pharma, Inc. Alexis Gomez has stock ownership and options and was an employee of Recro Pharma, Inc at the time of this study. Timothy I. Melson, Sabry S. Ayad, and Jorge E. Marcet do not have any conflicts of interest to disclose.

© 2019 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Figures

Figure 1
Figure 1
Consolidated Standards of Reporting Trials (CONSORT) flow diagram of patient disposition in study NCT02720692. IV indicates intravenous. *All treated subjects were to complete a final safety assessment by telephone 28 days following their last study dose; 8 subjects allocated to meloxicam IV 30 mg, and 3 subjects allocated to placebo were lost to follow‐up.
Figure 2
Figure 2
Total mean opioid consumption as measured by IV morphine equivalent dose at different time intervals during the study and over the treatment period. IV indicates intravenous.

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