Short-course antibiotic regimen compared to conventional antibiotic treatment for gram-positive cocci infective endocarditis: randomized clinical trial

INTERVENTION: Trade Name: BENZETACIL 2.400.000 Pharmaceutical Form: Powder and solution for solution for injection INN or Proposed INN: BENZYLPENICILLIN SODIUM CAS Number: 69‐57‐8 Concentration unit: IU international unit(s) Concentration type: equal Concentration number: 2400000‐ Trade Name: BENZETACIL 2.400.000 Pharmaceutical Form: Powder and solution for solution for injection INN or Proposed INN: BENZYLPENICILLIN SODIUM CAS Number: 69‐57‐8 Concentration unit: IU international unit(s) Concentration type: equal Concentration number: 2400000‐ Trade Name: CEFTRIAXONA FRESENIUS KABI 2 g POLVO PARA SOLUCIÓN PARA PERFUSIÓN EFG Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: CEFTRIAXONE CAS Number: 73384‐59‐5 Concentration unit: g gram(s) Concentration type: equal Concentration number: 2‐ Trade Name: CEFTRIAXONA FRESENIUS KABI 2 g POLVO PARA SOLUCIÓN PARA PERFUSIÓN EFG Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: CEFTRIAXONE CAS Number: 73384‐59‐5 Concentration unit: g gram(s) Concentration type: equal Concentration number: 2‐ Trade Name: GENTAMICINA BRAUN 3 mg/ml SOLUCION PARA PERFUSION INTRAVENOSA Pharmaceutical Form: Solution for infusion INN or Proposed INN: GENTAMICIN SULFATE CAS Number: 1405‐41‐0 Concen CONDITION: infective endocarditis Therapeutic area: Diseases [C] ‐ Cardiovascular Diseases [C14] SECONDARY OUTCOME: ; Secondary end point(s): ‐Perceived quality of life. We will measure changes in the mean score of SF‐12 between the time of randomization, 4 weeks after and 6 month.; ‐ Functional performance. We will measure changes the change in the mean score of short performance physical battery test (SPPB) between the time of randomization and 4 weeks after.; ‐ Total hospital length of stay in the next 6 months after the inclusion in the study, including admissions related or not related to IE.; ‐ Total cost per patient.; ‐ Clinical complications ap to 6 month after randomization.; Timepoint(s) of evaluation of this end point: 6 month PRIMARY OUTCOME: ; Primary end point(s): Composite endpoint of all‐cause mortality, unplanned cardiac surgery, symptomatic embolisms, and relapse by the index pathogen within 6 months after the intervention. Unplanned cardiac surgery is defined as surgery of the heart not planned before randomization.; Surgery due to sterile pericardial effusion or hemorrhage is not included. Embolic events are defined as any symptomatic embolic event that occurs after randomization.; Relapse is defined as the finding of any blood culture positive with the primary pathogen or appearance or progression of typical echocardiographic findings of IE (new appearance or enlargement of a vegetation, appearance of new periannular complications).; ; Secondary Objective: 1. Is superior compared to conventional antibiotic treatment regarding the perceived quality of life in the 4 weeks after the inclusion in the study.; 2. Is superior compared to conventional antibiotic treatment regarding the functional performance in the 4 weeks after the inclusion in the study.; 3. Diminish the risk of clinical complications related to prolonged hospital stay (nosocomial infections, intravascular catheter‐related infections), compared to conventional antibiotic treatment.; 4. Diminish total hospital length of stay in the next 6 months after the inclusion in the study, compared to conventional antibiotic treatment.; 5. Diminish with conventional antibiotic tetrament is more cost effectiveness; Main Objective: To compare the incidence of the composite endpoint of all‐cause mortality, unplanned cardiac surgery, symptomatic embolisms and relapses within 6 months after the inclusion, between patients with IE caused by gram‐positive cocci receiving a short course of 2 weeks of antibiotic therapy and those patients receiving conventional antibiotic therapy for 4‐6 weeks. Timepoint(s) of evaluation of this end point: 6 month INCLUSION CRITERIA: •Definite IE, according to modified ESC 2015 criteria, caused by gram‐positive cocci (staphylococci, streptococci and enterococci), including native, prosthetic valve IE and cardiac device‐related IE. •I8 years old or older. •Absence of fever, microbiological or analytical findings suggesting persistent infection after 24h of randomization. •Absence of locally uncontrolled infection signs (abscess, pseudoaneurysm, fistula, enlarging vegetation) at randomization, confirmed by recent transesophageal echocardiography (performed within 48 h of randomization). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for th