Multicenter, randomized, open-label non-inferiority trial, comparing two antibiotic therapy periods (3 versus 7 days) in patients with mild leptospirosis and seen at the hospital in 5 French overseas departments (Martinique, Guadeloupe, French Guiana, Reunion, Mayotte)

Condition studied

leptospirosis

Investigational medicinal product(s)

Eligibility

Primary endpoint

Treatment failure at 7 days from the beginning of antibiotic therapy as defined by occurrence of a complication described in the end points, Hemodynamic failure with onset of septic shock defined by persisting hypotension requiring vasopressor amines to maintain mean arterial pressure ≥65 mm Hg and blood lactates >2 mmol/L despite adequate volume resuscitation, Hematologic failure with hemoglobin <7 g / dL requiring red blood cell transfusion or platelets < 20 G / L requiring platelet transfusion, Ventilatory failure defined by PaO2 / Fi O2 ratio <300 mmHg or resort to mechanical ventilation, Renal failure defined by serum creatinine > 301 μmol / L or resort to renal dialysis, Hepatic failure defined by total bilirubinemia> 101 μmol / L, Heart failure (eg: ECG anomalies, myocarditis, cardiogenic shock), Neurologic affection such as meningitis, encephalitis, intracerebral hemorragia, stroke, Ocular symptoms such as uveitis, Hemoptysis, lesional pulmonary oedema for pulmonary affection, Hemorrhagic syndrome, Treatment failure at 7 days from the beginning of antibiotic therapy, as defined by continued fever (body temperature >38°C) 5 days after the start of antibiotic therapy, or fever reappearance (body temperature >38°C) observed 24 hours after initial apyrexia (body temperature <38°C). Both cases exclude fever due to a cause not attributable to leptospirosis infection., Treatment failure at 7 days from the beginning of antibiotic therapy, as defined by death

Endpoint detail

Evolution of clinical characteristics according to 3-day versus 7-day treatment duration: measure of body temperature , assessment of functional signs, no evolution of infection at 21 days from start of antibiotic therapy [Absence of clinical symptoms (jaundice, nausea, abdominal pain, myalgia, and arthlagia), normalization of biological parameters (creatinine, bilirubin, platelets, hemoglobin], quality of life criteria evaluated by the EQ5D questionnaire, Evolution of biological characteristics according to 3-day versus 7-day treatment duration (regression of biological inflammatory syndrome, improved renal, hepato-biliary and hematologic functions), Length of hospital stay according to 3-day versus 7-day treatment duration, Factors associated with treatment failure (serogroup, genotype, quantitative leptospiremia at start of antibiotic therapy, quantitative leptospiremia at 3 days from start of antibiotic therapy, delay between symptom onset and beginning of treatment, presence of co-morbidities), Treatment toxicity assessed by the occurrence of Jarisch-Herxheimer reactions, as well as adverse reaction reporting based on a standardized and internationally recognized toxicity table for adults