Oral Antimicrobial Treatment vs. Outpatient Parenteral for Infective Endocarditis
Phase 4
Recruiting
- Conditions
- Endocarditis Infective
- Interventions
- Drug: Fusidic Acid Only Product in Oral Dose FormDrug: Fusidic Acid Only Product in Parenteral Dose Form
- Registration Number
- NCT05398679
- Lead Sponsor
- Fundacion Clinic per a la Recerca Biomédica
- Brief Summary
Non-inferiority trial to determine whether partial oral treatment is non-inferior to OPAT(Outpatient parenteral therapy) in patients diagnosed with infective endocarditis
- Detailed Description
The trial will include patients diagnosed with left-side Infective Endocarditis according to the modified Duke criteria, with ≥10 days of appropriate parenteral antibiotic treatment overall and at least one week of appropriate parenteral treatment after valve surgery
The patients will be randomized in two arms, one with oral antibiotic therapy and the other one with outpatient parenteral therapy
This trial aims to demonstrate the non-inferiority of outpatient oral antibiotic therapy in comparison with outpatient parenteral antibiotic treatment (OPAT), to improve the quality of life of infective endocarditis (IE) patients, and to reduce the cost of the intervention without increasing morbidity and mortality rates
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 360
Inclusion Criteria
- Left-sided native or prosthetic infective endocarditis based on the modified Duke criteria infected with one of the following nonresistant microorganisms: Non-resistant streptococci and other gram positive cocci,e.g., Granulicatella and Abiotrophia; Enterococcus faecalis; Staphylococcus aureus;coagulase-negative staphylococci and HACEK group.
- Male or female 18 years old or older.
- 10 days or more of appropriate parenteral antibiotic treatment overall and at least one week of appropriate parenteral treatment after value surgery.
- Temperature inferior to 38ºC for more than two days. 5. C-reactive protein dropped to <25% of peak value or <20 mg/l, and white blood cell count <15x10^9/l during antibiotic treatment
- Transthoracic / transesophageal echocardiography performed within 48 hours of randomization
Exclusion Criteria
- Body mass index >40
- Concomitant infection requiring intravenous antibiotic therapy
- Inability to give informed consent to participation
- Suspicion of reduced absorption of oral treatment due to abdominal disorder
- Microorganisms with no oral combinations for treatment (two active antibiotics of different families)
- Any immunosuppressive disease or any medical condition at the discretion of the investigator that may preclude oral or OPAT therapy
- No family or appropriate home support
- Reduced compliance
- Women of childbearing potential with a positive pregnancy test, or participants (male or female) who wish to plan a pregnancy during the trial period
- Women in lactancy period
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description OPAT Levofloxacin Injection Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve parenteral antibiotics until the end of treatment. OPAT Tedizolid Injection Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve parenteral antibiotics until the end of treatment. Oral Therapy Levofloxacin Oral Tablet Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve oral antibiotics until the end of treatment. Oral Therapy Tedizolid Oral Tablet Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve oral antibiotics until the end of treatment. OPAT Sulfamethoxazole / Trimethoprim Injectable Product Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve parenteral antibiotics until the end of treatment. Oral Therapy Amoxicillin Capsules Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve oral antibiotics until the end of treatment. Oral Therapy Dicloxacillin Oral Capsule Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve oral antibiotics until the end of treatment. Oral Therapy Linezolid Oral Tablet Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve oral antibiotics until the end of treatment. OPAT Linezolid Injectable Product Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve parenteral antibiotics until the end of treatment. OPAT Ciprofloxacin Injection Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve parenteral antibiotics until the end of treatment. Oral Therapy Clindamycin Oral Capsule Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve oral antibiotics until the end of treatment. OPAT Moxifloxacin Injectable Product Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve parenteral antibiotics until the end of treatment. OPAT Clindamycin Injection Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve parenteral antibiotics until the end of treatment. OPAT Rifampicin Only Product in Parenteral Dose Form Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve parenteral antibiotics until the end of treatment. Oral Therapy Ciprofloxacin Tablets Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve oral antibiotics until the end of treatment. Oral Therapy Moxifloxacin tablet Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve oral antibiotics until the end of treatment. OPAT Fusidic Acid Only Product in Parenteral Dose Form Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve parenteral antibiotics until the end of treatment. Oral Therapy Rifampicin Only Product in Oral Dose Form Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve oral antibiotics until the end of treatment. Oral Therapy Fusidic Acid Only Product in Oral Dose Form Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve oral antibiotics until the end of treatment. Oral Therapy Sulfamethoxazole / Trimethoprim Oral Tablet [Bactrim] Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve oral antibiotics until the end of treatment. Oral Therapy Cefaclor Capsules Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve oral antibiotics until the end of treatment. OPAT Cefaclor Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve parenteral antibiotics until the end of treatment. OPAT Dicloxacillin Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve parenteral antibiotics until the end of treatment. OPAT Amoxicillin Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve parenteral antibiotics until the end of treatment.
- Primary Outcome Measures
Name Time Method Non-inferiority of outpatient oral vs parenteral antibiotic therapy measured by the number of patients requiring cardiac surgery At any time during the study duration (up to 24 months) Non-inferiority of outpatient oral vs parenteral antibiotic therapy measured by the number of all-cause mortality At any time during the study duration (up to 24 months) Non-inferiority of outpatient oral vs parenteral antibiotic therapy measured by the number of relapses of Infective Endocarditis within 6 months from diagnosis of Infective Endocarditis Non-inferiority of outpatient oral vs parenteral antibiotic therapy measured by the number of unplanned hospitalizations At any time during the study duration (up to 24 months)
- Secondary Outcome Measures
Name Time Method Quality of life and patient satisfaction of infective endocarditis patients. It will be measured through the standardized Saillen questionnaire of antibiotic treatment satisfaction At any time during the study duration (up to 24 months) The complications related to parenteral and oral administration of antibiotics will be measured through the number of antibiotic adverse reactions, catheter-related adverse events, and number of superinfections At any time during the study duration (up to 24 months) such as antibiotic or catheter-related adverse events e.g.,phlebitis and line-related bloodstream infections, and superinfections
Costs of both interventions, measured through a pharmaco-economic sub-study including direct and indirect costs, following the methodology described by Lacroix A et al Med Mal Infect. 2014 At any time during the study duration (up to 24 months) through a pharmacoeconomic analysis
Trial Locations
- Locations (20)
Hospital Virgen de la Macarena
🇪🇸Sevilla, Andalucía, Spain
Hospital Virgen del Rocío
🇪🇸Sevilla, Andalucía, Spain
Parc Taulí Hospital Universitari
🇪🇸Sabadell, Barcelona, Spain
Hospital Mútua de Terrassa
🇪🇸Terrassa, Barcelona, Spain
Hospital Universitario de Cruces
🇪🇸Barakaldo, Bizcaia, Spain
Hospital Universitario Marqués de Valdecilla
🇪🇸Santander, Cantabria, Spain
Hospital Universitario de Donostia
🇪🇸Donostia, Guipuzcoa, Spain
Hospital Son Espases
🇪🇸Palma De Mallorca, Illes Balears, Spain
Hospital San Pedro
🇪🇸Logroño, La Rioja, Spain
Hospital Virgen de Arrixaca
🇪🇸El Palmar, Murcia, Spain
Hospital universitario de Canarias
🇪🇸La Laguna, Santa Cruz De Tenerife, Spain
Hospital General de Alicante
🇪🇸Alicante, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Hospital Sant Pau
🇪🇸Barcelona, Spain
Hospital Bellvitge
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitari i Politècnic La Fe
🇪🇸València, Spain