Endocarditis Infective
Conditions
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
Interventions
DRUGCefaclor
cefaclor intravenous 2 gr/day
500-750 mg/12 hrs (maximum 3g x day)
DRUGCiprofloxacin Injection
1200 mg/day maximum dose IV
DRUGClindamycin Oral Capsule
600 mg/8 hours (maximum 1.800 mg x day)
600 mg/8 hours (maximum 1.800 mg x day) IV
1g/8 hours (maximum 4 gr day)
DRUGDicloxacillin
1g/8 hours (maximum 4 g x day) IV
DRUGFusidic Acid Only Product in Oral Dose Form
0,750g/12 hours (maximum 1,5 g x day)
DRUGFusidic Acid Only Product in Parenteral Dose Form
0,75 g/12 hours (maximum 1,5 g x day)
0.5g/12-24hours (maximum 1 g x day)
0.5g/12-24hours (maximum 1 g x day)
0,6 g/12 hours (maximum 1200 mg x day)
DRUGLinezolid Injectable Product
0,6 g/12 hours (maximum 1200 mg x day)
0,4 g/day (maximum 400 mg x day)
DRUGMoxifloxacin Injectable Product
0,4 g/day (maximum 400 mg x day)
DRUGRifampicin Only Product in Oral Dose Form
0,3-0,5 g/12 hours (maximum 1200 mg x day)
DRUGRifampicin Only Product in Parenteral Dose Form
0,3-0,6 g/12 hours (maximum 1200 mg x day)
DRUGSulfamethoxazole / Trimethoprim Oral Tablet [Bactrim]
sulfamethoxazole 1600 mg/trimethoprin 320 mg (maximum x day)
DRUGSulfamethoxazole / Trimethoprim Injectable Product
sulfamethoxazole 1600 mg/trimethoprin 320 mg (maximum x day)
DRUGTedizolid Oral Tablet
200 mg tedizolid (maximum x day)
DRUGTedizolid Injection
200 mg (maximum x day)
1 gr/6 hours (4 g x day)
DRUGAmoxicillin
1 gr/6 hours (4 g x day) Intravenous
DRUGCefaclor Capsules
2 gr/day
Sponsors
Fundacion Clinic per a la Recerca Biomédica
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
National multi-center study, open, controlled, and randomized
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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) |
| 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 patients requiring cardiac surgery | At any time during the study duration (up to 24 months) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
| 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 |
| 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 |
Countries
Spain
Contacts
CONTACTAnna Cruceta
CONTACTLaura Burunat
Outcome results
None listed