FOVOCIP study: a multicenter randomized trial of fosfomycin versus ciprofloxacin for febrile neutropenia in hematologic patients-efficacy and microbiologic safety.

BACKGROUND: Multidrug-resistant Gram-negative bacterial (MRGNB) infections represent a major public health threat. Cancer patients and, among them, hematological patients are most vulnerable to these infections. Gut colonization by MRGNB is a common phenomenon occurring during hospitalization and chemotherapy exposure. In the neutropenic phase that occurs after chemotherapy, MRGNB translocation occurs increasing patient's mortality. Fluoroquinolone prophylaxis with ciprofloxacin or levofloxacin efficacy is now being questioned due to the increase of incidence in MRGNB. METHODS: A phase III randomized, controlled, clinical trial, open-label parallel-group with a 1:1 ratio, aimed to demonstrate the non-inferiority of oral fosfomycin versus oral ciprofloxacin for febrile neutropenia prevention in patients with acute leukemia (AL) or hematopoietic cell transplant (HSC) receptors. Weekly surveillance cultures are planned to detect gut colonization. Changes in fecal microbiome at the beginning and end of prophylaxis will also be analyzed. DISCUSSION: This trial will provide evidence of the efficacy of an alternative drug to ciprofloxacin for febrile neutropenia prevention in high-risk hematological patients. The battery of planned microbiological studies will allow us to evaluate prospectively the microbiological safety of both pharmacological strategies in terms of the selection of MRGNB occurring in each arm. In addition, valuable information on the way in which each drug changes the fecal microbiome of the patients throughout the treatment will be generated. TRIAL REGISTRATION: Clinical trials NCT05311254, Registered on 5 April 2022, https://clinicaltrials.gov/ct2/show/NCT05311254?term=FOVOCIP&cntry=ES&draw=2&rank=1 . PROTOCOL VERSION: 3.0, dated 20 May 2022.

Usefulness of Early Treatment With Melatonin to Reduce Infarct Size in Patients With ST-Segment Elevation Myocardial Infarction Receiving Percutaneous Coronary Intervention (From the Melatonin Adjunct in the Acute Myocardial Infarction Treated With Angioplasty Trial).

Melatonin, an endogenously produced hormone, might potentially limit the ischemia reperfusion injury and improve the efficacy of mechanical reperfusion with primary percutaneous coronary intervention (pPCI) in ST-segment elevation myocardial infarction (STEMI). This study was aimed to evaluate whether the treatment effect of melatonin therapy in patients with STEMI is influenced by the time to administration. We performed a post hoc analysis of the Melatonin Adjunct in the Acute Myocardial Infarction Treated With Angioplasty trial (NCT00640094), which randomized STEMI patients to melatonin (intravenous and intracoronary bolus) or placebo during pPCI. Randomized patients were divided into tertiles according to symptoms onset to balloon time: first tertile (136 ± 23 minutes), second tertile (196 ± 19 minutes), and third tertile (249 ± 41 minutes). Magnetic resonance imaging was performed within 1 week after pPCI. A total of 146 patients presenting with STEMI within 360 minutes of chest pain onset were randomly allocated to intravenous and intracoronary melatonin or placebo during pPCI. In the first tertile, the infarct size was significantly smaller in the melatonin-treated subjects compared with placebo (14.6 ± 14.2 vs 24.9 ± 9.0%; p = 0.003). Contrariwise, treatment with melatonin was associated with a larger infarct size in the group of patients included in the third tertile (20.5 ± 8.7% vs 11.2 ± 5.2%; p = 0.001), resulting in a significant interaction (p = 0.001). In conclusion, the administration of melatonin in patients with STEMI who presented early after symptom onset was associated with a significant reduction in the infarct size after pPCI.