Oral Antimicrobial Treatment vs. Outpatient Parenteral for Infective Endocarditis

NCT ID: NCT05398679

Last Updated: 2025-03-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

360 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-17

Study Completion Date

2027-12-30

Brief Summary

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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

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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

Conditions

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Endocarditis Infective

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

National multi-center study, open, controlled, and randomized
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Cefaclor

Intervention Type DRUG

cefaclor intravenous 2 gr/day

Ciprofloxacin Injection

Intervention Type DRUG

1200 mg/day maximum dose IV

Clindamycin Injection

Intervention Type DRUG

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

Dicloxacillin

Intervention Type DRUG

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

Fusidic Acid Only Product in Parenteral Dose Form

Intervention Type DRUG

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

Levofloxacin Injection

Intervention Type DRUG

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

Linezolid Injectable Product

Intervention Type DRUG

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

Moxifloxacin Injectable Product

Intervention Type DRUG

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

Rifampicin Only Product in Parenteral Dose Form

Intervention Type DRUG

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

Sulfamethoxazole / Trimethoprim Injectable Product

Intervention Type DRUG

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

Tedizolid Injection

Intervention Type DRUG

200 mg (maximum x day)

Amoxicillin

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Ciprofloxacin Tablets

Intervention Type DRUG

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

Clindamycin Oral Capsule

Intervention Type DRUG

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

Dicloxacillin Oral Capsule

Intervention Type DRUG

1g/8 hours (maximum 4 gr day)

Fusidic Acid Only Product in Oral Dose Form

Intervention Type DRUG

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

Levofloxacin Oral Tablet

Intervention Type DRUG

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

Linezolid Oral Tablet

Intervention Type DRUG

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

Moxifloxacin tablet

Intervention Type DRUG

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

Rifampicin Only Product in Oral Dose Form

Intervention Type DRUG

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

Sulfamethoxazole / Trimethoprim Oral Tablet [Bactrim]

Intervention Type DRUG

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

Tedizolid Oral Tablet

Intervention Type DRUG

200 mg tedizolid (maximum x day)

Amoxicillin Capsules

Intervention Type DRUG

1 gr/6 hours (4 g x day)

Cefaclor Capsules

Intervention Type DRUG

2 gr/day

Interventions

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Cefaclor

cefaclor intravenous 2 gr/day

Intervention Type DRUG

Ciprofloxacin Tablets

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

Intervention Type DRUG

Ciprofloxacin Injection

1200 mg/day maximum dose IV

Intervention Type DRUG

Clindamycin Oral Capsule

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

Intervention Type DRUG

Clindamycin Injection

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

Intervention Type DRUG

Dicloxacillin Oral Capsule

1g/8 hours (maximum 4 gr day)

Intervention Type DRUG

Dicloxacillin

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

Intervention Type DRUG

Fusidic Acid Only Product in Oral Dose Form

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

Intervention Type DRUG

Fusidic Acid Only Product in Parenteral Dose Form

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

Intervention Type DRUG

Levofloxacin Oral Tablet

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

Intervention Type DRUG

Levofloxacin Injection

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

Intervention Type DRUG

Linezolid Oral Tablet

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

Intervention Type DRUG

Linezolid Injectable Product

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

Intervention Type DRUG

Moxifloxacin tablet

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

Intervention Type DRUG

Moxifloxacin Injectable Product

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

Intervention Type DRUG

Rifampicin Only Product in Oral Dose Form

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

Intervention Type DRUG

Rifampicin Only Product in Parenteral Dose Form

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

Intervention Type DRUG

Sulfamethoxazole / Trimethoprim Oral Tablet [Bactrim]

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

Intervention Type DRUG

Sulfamethoxazole / Trimethoprim Injectable Product

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

Intervention Type DRUG

Tedizolid Oral Tablet

200 mg tedizolid (maximum x day)

Intervention Type DRUG

Tedizolid Injection

200 mg (maximum x day)

Intervention Type DRUG

Amoxicillin Capsules

1 gr/6 hours (4 g x day)

Intervention Type DRUG

Amoxicillin

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

Intervention Type DRUG

Cefaclor Capsules

2 gr/day

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fundacion Clinic per a la Recerca Biomédica

OTHER

Sponsor Role lead

Responsible Party

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Anna Cruceta

Project Manager Clinical Trial Unit

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Hospital Virgen de la Macarena

Seville, Andalusia, Spain

Site Status RECRUITING

Hospital Virgen del Rocío

Seville, Andalusia, Spain

Site Status RECRUITING

Hospital Son Espases

Palma de Mallorca, Balearic Islands, Spain

Site Status RECRUITING

Parc Taulí Hospital Universitari

Sabadell, Barcelona, Spain

Site Status RECRUITING

Hospital Mútua de Terrassa

Terrassa, Barcelona, Spain

Site Status RECRUITING

Hospital Universitario de Cruces

Barakaldo, Bizcaia, Spain

Site Status RECRUITING

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, Spain

Site Status RECRUITING

Hospital Universitario de Donostia

Donostia / San Sebastian, Guipuzcoa, Spain

Site Status RECRUITING

Hospital San Pedro

Logroño, La Rioja, Spain

Site Status RECRUITING

Hospital Virgen de Arrixaca

El Palmar, Murcia, Spain

Site Status RECRUITING

Hospital universitario de Canarias

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

Site Status RECRUITING

Hospital General de Alicante

Alicante, , Spain

Site Status RECRUITING

Hospital del Mar

Barcelona, , Spain

Site Status RECRUITING

Hospital Clinic i Provincial de Barcelona

Barcelona, , Spain

Site Status RECRUITING

Hospital Sant Pau

Barcelona, , Spain

Site Status RECRUITING

Hospital Bellvitge

Barcelona, , Spain

Site Status RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Site Status RECRUITING

Hospital Ramón y Cajal

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario La Paz

Madrid, , Spain

Site Status RECRUITING

Hospital Universitari i Politècnic La Fe

Valencia, , Spain

Site Status NOT_YET_RECRUITING

Countries

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Spain

Central Contacts

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Anna Cruceta

Role: CONTACT

+34 932275400 ext. 4380

Laura Burunat

Role: CONTACT

+34 932275400 ext. 4198

Facility Contacts

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Laura Burunat, Chemistry

Role: primary

932275400 ext. 4198

Laura Burunat

Role: primary

932275400 ext. 4198

Laura Burunat, Chemistry

Role: primary

932275400 ext. 4198

Laura Burunat, Chemistry

Role: primary

932275400 ext. 4198

Laura Burunat, Chemistry

Role: primary

932275400 ext. 4198

Laura Burunat, Chemistry

Role: primary

932275400 ext. 4198

Laura Burunat, Chemistry

Role: primary

932275400 ext. 4198

Laura Burunat Ruesgas, Chemistry

Role: primary

932275400 ext. 4198

Laura Burunat, Chemistry

Role: primary

932275400 ext. 4198

Laura Burunat, Chemistry

Role: primary

932275400 ext. 4198

Laura Burunat, Chemistry

Role: primary

932275400 ext. 4198

Laura Burunat, Chemistry

Role: primary

932275400 ext. 4198

Laura Burunat, Chemistry

Role: primary

932275400 ext. 4198

Anna Cruceta, MD

Role: primary

+34 932275400 ext. 4380

Laura Burunat

Role: backup

+34 932275400 ext. 4198

Laura Burunat, Chemistry

Role: primary

932275400 ext. 4198

Laura Burunat, Chemistry

Role: primary

932275400 ext. 4198

Laura Burunat, Chemistry

Role: primary

932275400 ext. 4198

Laura Burunat, Chemistry

Role: primary

932275400 ext. 4198

Laura Burunat, Chemistry

Role: primary

932275400 ext. 4198

Laura Burunat, Chemistry

Role: primary

932275400 ext. 4198

References

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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.

Reference Type DERIVED
PMID: 40024946 (View on PubMed)

Other Identifiers

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OraPAT-IE GAMES

Identifier Type: -

Identifier Source: org_study_id

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