Oral Antimicrobial Treatment vs. Outpatient Parenteral for Infective Endocarditis

NCT05398679 | Recruiting Phase 4

• 1 other identifier: OraPAT-IE GAMES
• Study Type: interventional
• Target: 360
• Locations: 1 country
• Sites: 20

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

Conditions

Endocarditis Infective

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (3)

• 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)

• 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)

Study Arms (2)

OPAT

ACTIVE COMPARATOR

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; 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

Oral Therapy

EXPERIMENTAL

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; 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

Interventions

Cefaclor DRUG

cefaclor intravenous 2 gr/day

OPAT

Ciprofloxacin Tablets DRUG

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

Oral Therapy

Ciprofloxacin Injection DRUG

1200 mg/day maximum dose IV

OPAT

Clindamycin Oral Capsule DRUG

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

Oral Therapy

Clindamycin Injection DRUG

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

OPAT

Dicloxacillin Oral Capsule DRUG

1g/8 hours (maximum 4 gr day)

Oral Therapy

Dicloxacillin DRUG

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

OPAT

Fusidic Acid Only Product in Oral Dose Form DRUG

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

Oral Therapy

Fusidic Acid Only Product in Parenteral Dose Form DRUG

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

OPAT

Levofloxacin Oral Tablet DRUG

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

Oral Therapy

Levofloxacin Injection DRUG

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

OPAT

Linezolid Oral Tablet DRUG

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

Oral Therapy

Linezolid Injectable Product DRUG

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

OPAT

Moxifloxacin tablet DRUG

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

Oral Therapy

Moxifloxacin Injectable Product DRUG

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

OPAT

Rifampicin Only Product in Oral Dose Form DRUG

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

Oral Therapy

Rifampicin Only Product in Parenteral Dose Form DRUG

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

OPAT

Sulfamethoxazole / Trimethoprim Oral Tablet [Bactrim] DRUG

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

Oral Therapy

Sulfamethoxazole / Trimethoprim Injectable Product DRUG

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

OPAT

Tedizolid Oral Tablet DRUG

200 mg tedizolid (maximum x day)

Oral Therapy

Tedizolid Injection DRUG

200 mg (maximum x day)

OPAT

Amoxicillin Capsules DRUG

1 gr/6 hours (4 g x day)

Oral Therapy

Amoxicillin DRUG

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

OPAT

Cefaclor Capsules DRUG

2 gr/day

Oral Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fundacion Clinic per a la Recerca Biomédica: lead

Study Sites (20)

Hospital General de Alicante

Alicante, Alicante, 03010, Spain

RECRUITING

Hospital Virgen de la Macarena

Seville, Andalusia, 41009, Spain

RECRUITING

Hospital Virgen del Rocío

Seville, Andalusia, 41013, Spain

RECRUITING

Hospital Son Espases

Palma de Mallorca, Balearic Islands, 07120, Spain

RECRUITING

Hospital del Mar

Barcelona, Barcelona, 08003, Spain

RECRUITING

Hospital Clinic i Provincial de Barcelona

Barcelona, Barcelona, 08036, Spain

RECRUITING

Hospital Sant Pau

Barcelona, Barcelona, 08041, Spain

RECRUITING

Hospital Bellvitge

Barcelona, Barcelona, 08907, Spain

RECRUITING

Parc Taulí Hospital Universitari

Sabadell, Barcelona, 08208, Spain

RECRUITING

Hospital Mútua de Terrassa

Terrassa, Barcelona, 08221, Spain

RECRUITING

Hospital Universitario de Cruces

Barakaldo, Bizcaia, 48903, Spain

RECRUITING

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

RECRUITING

Hospital Universitario de Donostia

Donostia / San Sebastian, Guipuzcoa, 20014, Spain

RECRUITING

Hospital San Pedro

Logroño, La Rioja, 26006, Spain

RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, Madrid, 28007, Spain

RECRUITING

Hospital Ramón y Cajal

Madrid, Madrid, 28034, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

RECRUITING

Hospital Virgen de Arrixaca

El Palmar, Murcia, 30120, Spain

RECRUITING

Hospital universitario de Canarias

San Cristóbal de La Laguna, Santa Cruz de Tenerife, 38320, Spain

RECRUITING

Hospital Universitari i Politècnic La Fe

Valencia, València, 46009, Spain

NOT YET RECRUITING

Related Publications (1)

• 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, Navarro D, Moreno A, Sala C, Ambrosioni J, Miro JM; OraPAT-IE GAMES Investigators. Oral vs. Outpatient Parenteral Antimicrobial Treatment for Infective Endocarditis: Study Protocol for the Spanish OraPAT-IE GAMES Trial. Infect Dis Ther. 2025 Mar;14(3):643-655. doi: 10.1007/s40121-025-01110-9. Epub 2025 Mar 1.

  PMID: 40024946 DERIVED

MeSH Terms

Conditions

Endocarditis

Interventions

Cefaclor; Ciprofloxacin; Clindamycin; Dicloxacillin; Dosage Forms; Injections; Levofloxacin; Linezolid; Moxifloxacin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; tedizolid; Amoxicillin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Cephalexin; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Lincomycin; Lincosamides; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Glycosides; Carbohydrates; Cloxacillin; Oxacillin; Penicillins; Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques; Drug Administration Routes; Drug Therapy; Therapeutics; Ofloxacin; Acetamides; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Benzenesulfonamides; Sulfonamides; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Pyrimidines; Drug Combinations; Ampicillin; Penicillin G

Central Study Contacts

Anna Cruceta

CONTACT

+34 932275400; acruceta@clinic.cat

Laura Burunat

CONTACT

+34 932275400; burunat@clinic.cat

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Project Manager Clinical Trial Unit

Model Details: National multi-center study, open, controlled, and randomized

Study Record Dates

• First Submitted: May 4, 2022
• First Posted: June 1, 2022
• Study Start: August 17, 2022
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027
• Last Updated: February 25, 2026

Record last verified: 2026-02

Locations

ES (20)