Effect of Anakinra on Recurrent Pericarditis Among Patients With Colchicine Resistance and Corticosteroid Dependence: The AIRTRIP Randomized Clinical Trial.

Importance: Anakinra, an interleukin 1ß recombinant receptor antagonist, may have potential to treat colchicine-resistant and corticosteroid-dependent recurrent pericarditis. Objective: To determine the efficacy of anakinra for colchicine-resistant and corticosteroid-dependent recurrent pericarditis. Design, Setting, and Participants: The Anakinra-Treatment of Recurrent Idiopathic Pericarditis (AIRTRIP) double-blind, placebo-controlled, randomized withdrawal trial (open label with anakinra followed by a double-blind withdrawal step with anakinra or placebo until recurrent pericarditis occurred) conducted among 21 consecutive patients enrolled at 3 Italian referral centers between June and November 2014 (end of follow-up, October 2015). Included patients had recurrent pericarditis (with ≥3 previous recurrences), elevation of C-reactive protein, colchicine resistance, and corticosteroid dependence. Interventions: Anakinra was administered at 2 mg/kg per day, up to 100 mg, for 2 months, then patients who responded with resolution of pericarditis were randomized to continue anakinra (n = 11) or switch to placebo (n = 10) for 6 months or until a pericarditis recurrence. Main Outcomes and Measures: The primary outcomes were recurrent pericarditis and time to recurrence after randomization. Results: Eleven patients (7 female) randomized to anakinra had a mean age of 46.5 (SD, 16.3) years; 10 patients (7 female) randomized to placebo had a mean age of 44 (SD, 12.5) years. All patients were followed up for 12 months. Median follow-up was 14 (range, 12-17) months. Recurrent pericarditis occurred in 9 of 10 patients (90%; incidence rate, 2.06% of patients per year) assigned to placebo and 2 of 11 patients (18.2%; incidence rate, 0.11% of patients per year) assigned to anakinra, for an incidence rate difference of -1.95% (95% CI, -3.3% to -0.6%). Median flare-free survival (time to flare) was 72 (interquartile range, 64-150) days after randomization in the placebo group and was not reached in the anakinra group (P <.001). During anakinra treatment, 20 of 21 patients (95.2%) experienced transient local skin reactions: 1 (4.8%) herpes zoster, 3 (14.3%) transaminase elevation, and 1 (4.8%) ischemic optic neuropathy. No patient permanently discontinued the active drug. No adverse events occurred during placebo treatment. Conclusion and Relevance: In this preliminary study of patients with recurrent pericarditis with colchicine resistance and corticosteroid dependence, the use of anakinra compared with placebo reduced the risk of recurrence over a median of 14 months. Larger studies are needed to replicate these findings as well as to assess safety and longer-term efficacy. Trial Registration: clinicaltrials.gov Identifier: NCT02219828.

Caudal 0.2% ropivacaine is less effective during surgery than 0.2% levobupivacaine and 0.2% bupivacaine: a double-blind, randomized, controlled trial.

BACKGROUND: We hypothesized that without the analgesic effects of volatile anesthetics, caudal 0.20% ropivacaine would be less effective during surgical stimulation than 0.20% bupivacaine or 0.20% levobupivacaine. This trial was designed to examine whether the combination of a caudal block with 0.20% ropivacaine and i.v. anesthesia resulted in reduced analgesic efficacy during surgery compared with caudal 0.20% levobupivacaine or 0.20% bupivacaine in children. METHODS: Ninety ASA I-II children between 1 and 7 years old, scheduled for inguinal hernia repair or orchidopexy under propofol anesthesia were randomized to receive a caudal block with 1 ml x kg(-1) of 0.2% bupivacaine, 0.2% ropivacaine or 0.2% levobupivacaine. The primary outcome measure of the study was the clinical efficacy of the caudal block during surgery. Secondary outcome measures were postoperative pain relief and residual motor blockade. RESULTS: Four children were excluded and 86 were analyzed. The proportion of children with effective caudal block during surgery was significantly higher in children receiving levobupivacaine (26/28) or bupivacaine (27/29) compared with patients receiving ropivacaine (21/29) (P = 0.03). There were no significant differences among groups in the analgesic onset time (P = 0.1), incidence of residual motor blockade (P = 0.4), number of patients requiring analgesia after operation or in the time from caudal injection to the first administration of analgesic medication (P = 0.3). CONCLUSIONS: Combined with propofol anesthesia, 0.2% levobupivacaine and 0.2% bupivacaine are more effective than 0.2% ropivacaine for caudal use in children undergoing inguinal hernia repair or orchidopexy.