Antimicrobial for 7 or 14 Days for Febrile Urinary Tract Infection in Men: A Multicenter Noninferiority Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

BACKGROUND: The optimal duration of antimicrobial therapy for urinary tract infections (UTIs) in men remains controversial. METHODS: To compare 7 days to 14 days of total antibiotic treatment for febrile UTIs in men, this multicenter randomized, double-blind. placebo-controlled noninferiority trial enrolled 282 men from 27 centers in France. Men were eligible if they had a febrile UTI and urine culture showing a single uropathogen. Participants were treated with ofloxacin or a third-generation cephalosporin at day 1, then randomized at day 3-4 to either continue ofloxacin for 14 days total treatment, or for 7 days followed by placebo until day 14. The primary endpoint was treatment success, defined as a negative urine culture and the absence of fever and of subsequent antibiotic treatment between the end of treatment and 6 weeks after day 1. Secondary endpoints included recurrent UTI within weeks 6 and 12 after day 1, rectal carriage of antimicrobial-resistant Enterobacterales, and drug-related events. RESULTS: Two hundred forty participants were randomly assigned to receive antibiotic therapy for 7 days (115 participants) or 14 days (125 participants). In the intention-to-treat analysis, treatment success occurred in 64 participants (55.7%) in the 7-day group and in 97 participants (77.6%) in the 14-day group (risk difference, -21.9 [95% confidence interval, -33.3 to -10.1]), demonstrating inferiority. Adverse events during antibiotic therapy were reported in 4 participants in the 7-day arm and 7 in the 14-day arm. Rectal carriage of resistant Enterobacterales did not differ between both groups. CONCLUSIONS: A treatment with ofloxacin for 7 days was inferior to 14 days for febrile UTI in men and should therefore not be recommended. CLINICAL TRIALS REGISTRATION: NCT02424461; Eudra-CT: 2013-001647-32.

Effects of early high-dose erythropoietin on acute kidney injury following cardiac arrest: exploratory post hoc analyses from an open-label randomized trial.

BACKGROUND: Acute kidney injury (AKI) is frequent in patients resuscitated from cardiac arrest (CA) and may worsen outcome. Experimental data suggest a renoprotective effect by treating these patients with a high dose of erythropoietin (Epo) analogues. We aimed to evaluate the efficacy of epoetin alpha treatment on renal outcome after CA. METHODS: We did a post hoc analysis of the Epo-ACR-02 trial, which randomized patients with a persistent coma after a witnessed out-of-hospital CA. Only patients admitted in one intensive care unit were analysed. In the intervention group, patients received five intravenous injections of Epo spaced 12 h apart during the first 48 h, started as soon as possible after resuscitation. In the control group, patients received standard care without Epo. The main endpoint was the proportion of patients with persistent AKI defined by Kidney Disease: Improving Global Outcomes criteria at Day 2. Secondary endpoints included the occurrence of AKI through Day 7, estimated glomerular filtration rate (eGFR) at Day 28, haematological indices and adverse events. RESULTS: A total of 162 patients were included in the primary analysis (74 in the Epo group, 88 in the control group). Baseline characteristics were similar in the two groups. At Day 2, 52.8% of the patients (38/72) in the intervention group had an AKI, as compared with 54.4% of the patients (46/83) in the control group (P = 0.74). There was no significant difference between the two groups regarding the proportion of patients with AKI through Day 7. Among patients with persistent AKI at Day 2, 33% (4/12) in the intervention group had an eGFR <75 mL/min/1.73 m2 compared with 25% (3/12) in the control group at Day 28 (P = 0.99). We found no significant differences in haematological indices or adverse events. CONCLUSION: After CA, early administration of Epo did not confer any renal protective effect as compared with standard therapy.

Early High-Dose Erythropoietin Therapy After Out-of-Hospital Cardiac Arrest: A Multicenter, Randomized Controlled Trial.

BACKGROUND: Preliminary data suggested a clinical benefit in treating out-of-hospital cardiac arrest (OHCA) patients with a high dose of erythropoietin (Epo) analogs. OBJECTIVES: The authors aimed to evaluate the efficacy of epoetin alfa treatment on the outcome of OHCA patients in a phase 3 trial. METHODS: The authors performed a multicenter, single-blind, randomized controlled trial. Patients still comatose after a witnessed OHCA of presumed cardiac origin were eligible. In the intervention group, patients received 5 intravenous injections spaced 12 h apart during the first 48 h (40,000 units each, resulting in a maximal dose of 200,000 total units), started as soon as possible after resuscitation. In the control group, patients received standard care without Epo. The main endpoint was the proportion of patients in each group reaching level 1 on the Cerebral Performance Category (CPC) scale (survival with no or minor neurological sequelae) at day 60. Secondary endpoints included all-cause mortality rate, distribution of patients in CPC levels at different time points, and side effects. RESULTS: In total, 476 patients were included in the primary analysis. Baseline characteristics were similar in the 2 groups. At day 60, 32.4% of patients (76 of 234) in the intervention group reached a CPC 1 level, as compared with 32.1% of patients (78 of 242) in the control group (odds ratio: 1.01; 95% confidence interval: 0.68 to 1.48). The mortality rate and proportion of patients in each CPC level did not differ at any time points. Serious adverse events were more frequent in Epo-treated patients as compared with controls (22.6% vs. 14.9%; p = 0.03), particularly thrombotic complications (12.4% vs. 5.8%; p = 0.01). CONCLUSIONS: In patients resuscitated from an OHCA of presumed cardiac cause, early administration of erythropoietin plus standard therapy did not confer a benefit, and was associated with a higher complication rate. (High Dose of Erythropoietin Analogue After Cardiac Arrest [Epo-ACR-02]; NCT00999583).