Oral Antimicrobial Treatment vs. Outpatient Parenteral for Infective Endocarditis

Overview

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

• Drug Cefaclor
  cefaclor intravenous 2 gr/day
• Drug Ciprofloxacin Tablets
  500-750 mg/12 hrs (maximum 3g x day)
• Drug Ciprofloxacin Injection
  1200 mg/day maximum dose IV
• Drug Clindamycin Oral Capsule
  600 mg/8 hours (maximum 1.800 mg x day)
• Drug Clindamycin Injection
  600 mg/8 hours (maximum 1.800 mg x day) IV
• Drug Dicloxacillin Oral Capsule
  1g/8 hours (maximum 4 gr day)
• Drug Dicloxacillin
  1g/8 hours (maximum 4 g x day) IV
• Drug Fusidic Acid Only Product in Oral Dose Form
  0,750g/12 hours (maximum 1,5 g x day)
• Drug Fusidic Acid Only Product in Parenteral Dose Form
  0,75 g/12 hours (maximum 1,5 g x day)
• Drug Levofloxacin Oral Tablet
  0.5g/12-24hours (maximum 1 g x day)

Primary outcome measures

• Non-inferiority of outpatient oral vs parenteral antibiotic therapy measured by the number of unplanned hospitalizations [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: At any time during the study duration (up to 24 months)]

Secondary outcome measures (3)

• Quality of life and patient satisfaction of infective endocarditis patients. It will be measured through the standardized Saillen questionnaire of antibiotic treatment satisfaction [Time frame: 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 [Time frame: 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 [Time frame: At any time during the study duration (up to 24 months)]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 20 centers

• Hospital General de Alicante — Alicante
• Hospital Virgen de la Macarena — Seville
• Hospital Virgen del Rocío — Seville
• Hospital Son Espases — Palma de Mallorca
• Hospital del Mar — Barcelona
• Hospital Clinic i Provincial de Barcelona — Barcelona
• Hospital Sant Pau — Barcelona
• Hospital Bellvitge — Barcelona
• … and 12 more centers

Publications

• Cuervo G, Hernandez-Meneses M, de Alarcon A, Luque-Marquez R, Alonso-Socas MM, Lopez-Lirola A, Gonzalez-Ramallo V, Goikoetxea-Agirre AJ, Nicolas D, Goenaga MA, Merino E, Escrihuela-Vidal F, Martin-Davila P, Loeches B, Boix-Palop L, Gasch O, Camprecios M, Hernandez-Torres A, Garcia-Alvarez L, Pajaron M, Ribas MA, Blanes-Hernandez R, Lopez-Montesinos I, Lopez-Cortes LE, Vidal B, Fernandez-Pittol M, PMID 40024946

Identifiers

NCT: NCT05398679 · OraPAT-IE GAMES

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗