A multi-center, randomized, double-blind, parallel, placebo-controlled trial to evaluate the efficacy, safety, and pharmacokinetics of intravenous ibuprofen for the treatment of fever in critically ill and non-critically ill adults

INTRODUCTION: Hospitalized patients are often unable to ingest or tolerate oral antipyretics and recently an aqueous formulation of intravenous (IV) ibuprofen was approved by the US-FDA for the reduction of fever in adults. METHODS: We evaluated IV ibuprofen to reduce fever exceeding 101.0°F, measured as the percentage of subjects achieving a temperature <101.0°F at four hours after a single dose of IV ibuprofen vs. placebo. Secondary evaluations included the effect on temperature at 24 hours. Nine sites randomized patients to receive either a placebo or IV ibuprofen (100, 200, or 400 mg), and patients were given four hours for six doses. Subjects were excluded for platelet count <30 k and/or creatinine >3.0 mg/dL. RESULTS: At entry, there were no significant baseline differences between the IV ibuprofen group and placebo, n = 120. At four hours, the number (percentage) with T<101.0°F was: Placebo n = 9/28 (32%); 100 mg IV ibuprofen n = 19/31 (61%), P = 0.0264; 200 mg IV ibuprofen n = 21/30 (70%) P = 0.0043; 400 mg IV ibuprofen n = 24/31 (77%) P = 0.0005. A total of 53/120 patients (44%) were prospectively defined as critically ill at baseline and similar temperature reductions were observed in this subgroup. There were no statistically significant differences between treatment groups or when compared to placebo in transfusion, bleeding, renal failure or mortality. CONCLUSIONS: All doses of IV ibuprofen tested reduced fever at four hours and throughout the first 24 hours of dosing. The 400 mg dose was effective in lowering temperature to normal and maintaining this over the first 24 hours of dosing. IV ibuprofen was effective in reducing fevers in critically ill and non-critically ill groups. Following 24 hours of administration of IV ibuprofen, no clinically significant differences in any safety parameter including renal function or bleeding occurred through the 28-day follow-up period. TRIAL REGISTRATIONS: Clinicaltrials.gov registration number: NCT01131000.