OraPAT-IEGAMES: Oral Antimicrobial Treatment vs. Outpatient Parenteral for Infective Endocarditis

Sponsor

Fundacion Clinic per a la Recerca Biomédica (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05398679

Collaborator

(none)

360

Enrollment

Location

Arms

Anticipated Duration (Months)

11.6

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Endocarditis Infective	Drug: Cefaclor Drug: Ciprofloxacin Tablets Drug: Ciprofloxacin Injection Drug: Clindamycin Oral Capsule Drug: Clindamycin Injection Drug: Dicloxacillin Oral Capsule Drug: Dicloxacillin Drug: Fusidic Acid Only Product in Oral Dose Form Drug: Fusidic Acid Only Product in Parenteral Dose Form Drug: Levofloxacin Oral Tablet Drug: Levofloxacin Injection Drug: Linezolid Oral Tablet Drug: Linezolid Injectable Product Drug: Moxifloxacin tablet Drug: Moxifloxacin Injectable Product Drug: Rifampicin Only Product in Oral Dose Form Drug: Rifampicin Only Product in Parenteral Dose Form Drug: Sulfamethoxazole / Trimethoprim Oral Tablet [Bactrim] Drug: Sulfamethoxazole / Trimethoprim Injectable Product Drug: Tedizolid Oral Tablet Drug: Tedizolid Injection Drug: Amoxicillin Capsules Drug: Amoxicillin Drug: Cefaclor Capsules	Phase 4

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

360 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

National multi-center study, open, controlled, and randomizedNational multi-center study, open, controlled, and randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Oral Antimicrobial Treatment vs. Outpatient Parenteral for Infective Endocarditis

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Jun 30, 2024

Anticipated Study Completion Date :

Dec 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: OPAT 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.	Drug: Cefaclor cefaclor intravenous 2 gr/day Drug: Ciprofloxacin Injection 1200 mg/day maximum dose IV Drug: Clindamycin Injection 600 mg/8 hours (maximum 1.800 mg x day) IV Drug: Dicloxacillin 1g/8 hours (maximum 4 g x day) IV Drug: Fusidic Acid Only Product in Parenteral Dose Form 0,75 g/12 hours (maximum 1,5 g x day) Drug: Levofloxacin Injection 0.5g/12-24hours (maximum 1 g x day) Drug: Linezolid Injectable Product 0,6 g/12 hours (maximum 1200 mg x day) Drug: Moxifloxacin Injectable Product 0,4 g/day (maximum 400 mg x day) Drug: Rifampicin Only Product in Parenteral Dose Form 0,3-0,6 g/12 hours (maximum 1200 mg x day) Drug: Sulfamethoxazole / Trimethoprim Injectable Product sulfamethoxazole 1600 mg/trimethoprin 320 mg (maximum x day) Drug: Tedizolid Injection 200 mg (maximum x day) Drug: Amoxicillin 1 gr/6 hours (4 g x day) Intravenous
Experimental: Oral Therapy 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.	Drug: Ciprofloxacin Tablets 500-750 mg/12 hrs (maximum 3g x day) Drug: Clindamycin Oral Capsule 600 mg/8 hours (maximum 1.800 mg x day) Drug: Dicloxacillin Oral Capsule 1g/8 hours (maximum 4 gr day) Drug: Fusidic Acid Only Product in Oral Dose Form 0,750g/12 hours (maximum 1,5 g x day) Drug: Levofloxacin Oral Tablet 0.5g/12-24hours (maximum 1 g x day) Drug: Linezolid Oral Tablet 0,6 g/12 hours (maximum 1200 mg x day) Drug: Moxifloxacin tablet 0,4 g/day (maximum 400 mg x day) Drug: Rifampicin Only Product in Oral Dose Form 0,3-0,5 g/12 hours (maximum 1200 mg x day) Drug: Sulfamethoxazole / Trimethoprim Oral Tablet [Bactrim] sulfamethoxazole 1600 mg/trimethoprin 320 mg (maximum x day) Drug: Tedizolid Oral Tablet 200 mg tedizolid (maximum x day) Drug: Amoxicillin Capsules 1 gr/6 hours (4 g x day) Drug: Cefaclor Capsules 2 gr/day

Arm

Intervention/Treatment

Active Comparator: OPAT

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.

Drug: Cefaclor

cefaclor intravenous 2 gr/day

Drug: Ciprofloxacin Injection

1200 mg/day maximum dose IV

Drug: Clindamycin Injection

600 mg/8 hours (maximum 1.800 mg x day) IV

Drug: Dicloxacillin

1g/8 hours (maximum 4 g x day) IV

Drug: Fusidic Acid Only Product in Parenteral Dose Form

0,75 g/12 hours (maximum 1,5 g x day)

Drug: Levofloxacin Injection

0.5g/12-24hours (maximum 1 g x day)

Drug: Linezolid Injectable Product

0,6 g/12 hours (maximum 1200 mg x day)

Drug: Moxifloxacin Injectable Product

0,4 g/day (maximum 400 mg x day)

Drug: Rifampicin Only Product in Parenteral Dose Form

0,3-0,6 g/12 hours (maximum 1200 mg x day)

Drug: Sulfamethoxazole / Trimethoprim Injectable Product

sulfamethoxazole 1600 mg/trimethoprin 320 mg (maximum x day)

Drug: Tedizolid Injection

200 mg (maximum x day)

Drug: Amoxicillin

1 gr/6 hours (4 g x day) Intravenous

Experimental: Oral Therapy

Drug: Ciprofloxacin Tablets

500-750 mg/12 hrs (maximum 3g x day)

Drug: Clindamycin Oral Capsule

600 mg/8 hours (maximum 1.800 mg x day)

Drug: Dicloxacillin Oral Capsule

1g/8 hours (maximum 4 gr day)

Drug: Fusidic Acid Only Product in Oral Dose Form

0,750g/12 hours (maximum 1,5 g x day)

Drug: Levofloxacin Oral Tablet

0.5g/12-24hours (maximum 1 g x day)

Drug: Linezolid Oral Tablet

0,6 g/12 hours (maximum 1200 mg x day)

Drug: Moxifloxacin tablet

0,4 g/day (maximum 400 mg x day)

Drug: Rifampicin Only Product in Oral Dose Form

0,3-0,5 g/12 hours (maximum 1200 mg x day)

Drug: Sulfamethoxazole / Trimethoprim Oral Tablet [Bactrim]

sulfamethoxazole 1600 mg/trimethoprin 320 mg (maximum x day)

Drug: Tedizolid Oral Tablet

200 mg tedizolid (maximum x day)

Drug: Amoxicillin Capsules

1 gr/6 hours (4 g x day)

Drug: Cefaclor Capsules

2 gr/day

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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