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

Non-inferiority trial to determine whether partial oral treatment is non-inferior to OPAT(Outpatient parenteral therapy) in patients diagnosed with infective endocarditis

Study Overview

• Status: Not yet recruiting
• Conditions: Endocarditis Infective
• Intervention / Treatment: Drug: Cefaclor; Drug: Ciprofloxacin Injection; Drug: Clindamycin Injection; Drug: Dicloxacillin; Drug: Fusidic Acid Only Product in Parenteral Dose Form; Drug: Levofloxacin Injection; Drug: Linezolid Injectable Product; Drug: Moxifloxacin Injectable Product; Drug: Rifampicin Only Product in Parenteral Dose Form; Drug: Sulfamethoxazole / Trimethoprim Injectable Product; Drug: Tedizolid Injection; Drug: Amoxicillin; Drug: Ciprofloxacin Tablets; Drug: Clindamycin Oral Capsule; Drug: Dicloxacillin Oral Capsule; Drug: Fusidic Acid Only Product in Oral Dose Form; Drug: Levofloxacin Oral Tablet; Drug: Linezolid Oral Tablet; Drug: Moxifloxacin tablet; Drug: Rifampicin Only Product in Oral Dose Form; Drug: Sulfamethoxazole / Trimethoprim Oral Tablet [Bactrim]; Drug: Tedizolid Oral Tablet; Drug: Amoxicillin Capsules; Drug: Cefaclor Capsules

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 Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Anna Cruceta; Phone Number: 4380 +34 932275400; Email: acruceta@clinic.cat
• Study Contact Backup: Name: Laura Burunat; Phone Number: 4198 +34 932275400; Email: burunat@clinic.cat

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
    • Contact: Laura Burunat; Phone Number: 4198 +34 932275400; Email: burunat@clinic.cat
    • Contact: Anna Cruceta, MD; Phone Number: 4380 +34 932275400; Email: acruceta@clinic.cat
    • Principal Investigator: Juan Ambrosioni, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	through a pharmacoeconomic analysis	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	such as antibiotic or catheter-related adverse events e.g.,phlebitis and line-related bloodstream infections, and superinfections	At any time during the study duration (up to 24 months)

Collaborators and Investigators

• Sponsor: Fundacion Clinic per a la Recerca Biomédica

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2022
• Primary Completion (Anticipated): June 30, 2024
• Study Completion (Anticipated): December 30, 2024

Study Registration Dates

• First Submitted: May 4, 2022
• First Submitted That Met QC Criteria: May 26, 2022
• First Posted (Actual): June 1, 2022

Study Record Updates

• Last Update Posted (Actual): June 1, 2022
• Last Update Submitted That Met QC Criteria: May 26, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Cardiovascular Infections; Endocarditis, Bacterial; Endocarditis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Protein Synthesis Inhibitors; Cytochrome P-450 Enzyme Inducers; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral, Combined; Contraceptives, Oral; Contraceptive Agents, Female; Antiprotozoal Agents; Antiparasitic Agents; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antimalarials; Folic Acid Antagonists; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Dyskinesia Agents; Anti-Infective Agents, Urinary; Renal Agents; Cytochrome P-450 CYP2C8 Inhibitors; Linezolid; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination; Rifampin; Clindamycin; Clindamycin palmitate; Clindamycin phosphate; Ciprofloxacin; Amoxicillin; Levofloxacin; Ofloxacin; Trimethoprim; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination; Fusidic Acid; Oxazolidinones; Tedizolid; Dicloxacillin; Cefaclor
• Other Study ID Numbers: OraPAT-IE GAMES

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No