Early Intravenous to Oral Antibiotic Switch in Uncomplicated Staphylococcus Aureus Bacteraemia

NCT06336824 | Recruiting Phase 3 DMC

• 1 other identifier: EVOS 1.3 dated 12 March 2024
• Study Type: interventional
• Target: 290
• Locations: 1 country
• Sites: 12

Brief Summary

The Early Intravenous to Oral Antibiotic Switch in Uncomplicated Staphylococcus aureus Bacteraemia (EVOS) study is a multicentre, randomized, open-label, parallel group, phase 3, non-inferiority trial of early intravenous to oral antibiotic switch in comparison with standard intravenous antibiotic regime among patients with uncomplicated Staphylococcus aureus bacteraemia (SAB). The study is based on the hypothesis that an early switch from IV to oral antimicrobial therapy is non-inferior and safe compared to conventional minimum 14-day course of IV therapy in patients with low-risk uncomplicated SAB.

Conditions

Staphylococcus Aureus Bacteremia

Keywords

bacteremia; oral antibiotics; Staphylococcus aureus

Outcome Measures

Primary Outcomes (1)

• Rate of SAB-relapse

  defined as any new positive blood culture with S. aureus, and/or newly diagnosed metastatic S. aureus infection resulting from hematogenous dissemination

  90 days

Secondary Outcomes (5)

• Number of days of hospitalization

  90 days

• Rate of all-cause mortality

  90 days

• Rate of complications related to IV therapy

  90 days

• Rate of Clostridium difficile diarrhoea

  90 days

• Rate of adverse events

  30 days

Study Arms (2)

Early Oral Switch Therapy (EOS)

EXPERIMENTAL

Patients will switch from IV therapy to oral antibiotics for 7 to 11 days to achieve a total 14 days of definitive antimicrobial therapy for SAB. First choice oral antibiotics for MSSA and MRSA: Tab. Trimethoprim-sulfamethoxazole (TMP 10mg/kg/day) Alternative oral antibiotics for MSSA: Tab. Clindamycin 600mg TDS, Tab. Cephalexin 1gm QID, Tab Linezolid 600mg BD Alternative oral antibiotics for MRSA: Tab. Linezolid 600mg BD

Drug: Tab. Trimethoprim-sulfamethoxazole, Tab. Clindamycin, Tab. Cephalexin, or Tab. Linezolid

Standard IV therapy (SIV)

ACTIVE COMPARATOR

Patients will continue with IV therapy for 7 to 11 days to achieve a total 14 days of definitive antimicrobial therapy for SAB. First choice IV antibiotics for MSSA: IV Cloxacillin 2g every 4 or 6 hours Alternative IV antibiotics for MSSA: IV Cefazolin 2g TDS First choice IV antibiotics for MRSA: IV Vancomycin 15-20mg/kg BD Alternative IV antibiotics for MRSA: IV Ceftaroline 600mg TDS

Drug: IV Cloxacillin, IV Cefazolin, IV Vancomycin, or IV Ceftaroline

Interventions

Tab. Trimethoprim-sulfamethoxazole, Tab. Clindamycin, Tab. Cephalexin, or Tab. Linezolid DRUG

The choice of study drug will depend on the susceptibility of the respective isolate, expected drug interactions, contraindications, and expected side effects. Investigators will assess whether the "first-choice" regimen can be given and then consider the alternative regimen. The antibiotics can be switched from first choice to the respective alternative medications during the intervention period if clinically necessary. The route of administration must be maintained according to the randomized group.

Also known as: Bactrim, Dalacin, Ospexin, Zyvox

Early Oral Switch Therapy (EOS)

IV Cloxacillin, IV Cefazolin, IV Vancomycin, or IV Ceftaroline DRUG

The choice of study drug will depend on the susceptibility of the respective isolate, expected drug interactions, contraindications, and expected side effects. Investigators will assess whether the "first-choice" regimen can be given and then consider the alternative regimen. The antibiotics can be switched from first choice to the respective alternative medications during the intervention period if clinically necessary. The route of administration must be maintained according to the randomized group.

Also known as: Cloxacillin Sodium, Cefazolin Sandoz, Vancotex, Zinforo

Standard IV therapy (SIV)

Eligibility Criteria

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

You may qualify if:

• Blood culture positive for Staphylococcus aureus (S. aureus).
• Received 3 to 7 days of definitive IV antimicrobial therapy, defined as:
• Cloxacillin or cefazolin for methicillin-sensitive staphylococcus aureus (MSSA); Vancomycin or ceftaroline for methicillin-resistant staphylococcus aureus (MRSA).
• Proven in-vitro susceptibility and adequate dosing given (as determined by the principal investigator).
• Achieved clearance of bacteraemia, defined as at least one documented latest negative follow-up blood culture obtained within 72 hours after the initiation of definitive IV antimicrobial therapy.
• Achieved defervescence, defined as sustained body temperature ≤37.5°C within 48 hours before randomization.
• Able to provide written informed consent to participate trial.

You may not qualify if:

• Evidence of metastatic infection of S. aureus: for example, infective endocarditis, intraabdominal abscess, lung empyema, and osteomyelitis. Radiological investigations such as chest X-ray, ultrasound, echocardiogram, and CT scan are not mandatory prior to enrolment, but should be done at the discretion of the treating physician if clinically indicated.
• Septic shock, defined as hypotension requiring vasopressors to maintain MAP ≥65 mmHg despite adequate volume resuscitation.
• Received more than 5 days of non-study antibiotics as empirical therapy prior to enrolment.
• Polymicrobial bloodstream infection, defined as isolation of pathogens other than S. aureus from a blood culture obtained prior to randomization. Common skin contaminants such as coagulase-negative staphylococci, Bacillus spp., and diphtheroid will not be considered to represent polymicrobial infection.
• Known history of S. aureus infection within the past 3 months.
• Inability to tolerate oral therapy or poor absorption of oral medications, or not suitable for ongoing IV therapy (for example, difficult intravenous access)
• No options of oral antibiotic available for patient due to:
• In vitro resistance of S. aureus to all oral study drugs.
• Known contraindications to receive the active oral study drugs. For example, hypersensitivity reaction to trimethoprim-sulfamethoxazole, thrombocytopenia secondary to linezolid etc.
• Non-availability of oral study drugs at the study sites.
• Patient is concomitantly receiving oral antibiotics which are active against S. aureus. For example, trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia prophylaxis.
• Presence of a non-removable foreign body such as prosthetic heart valve, vascular graft, pacemaker, automated implantable cardioverter-defibrillator, ventriculoperitoneal shunt, prosthetic joint, and fracture fixation implant
• Failure or inability to remove intravascular catheter that is present when first positive blood culture was drawn.
• Known comorbidity that increased the risk of complicated infections:
• End-stage renal disease

Sponsors & Collaborators

• Clinical Research Centre, Malaysia: lead

Study Sites (12)

Hospital Sultanah Aminah

Johor Bahru, Johor, 80100, Malaysia

RECRUITING

Hospital Sultanah Bahiyah

Alor Star, Kedah, 05460, Malaysia

RECRUITING

Hospital Sultan Abdul Halim

Sungai Petani, Kedah, 08000, Malaysia

RECRUITING

Hospital Tuanku Ja'afar

Seremban, Negeri Sembilan, 70300, Malaysia

RECRUITING

Hospital Raja Permaisuri Bainun

Ipoh, Perak, 30450, Malaysia

RECRUITING

Hospital Pulau Pinang

George Town, Pulau Pinang, 10450, Malaysia

RECRUITING

Hospital Seberang Jaya

Seberang Jaya, Pulau Pinang, 13700, Malaysia

RECRUITING

Hospital Ampang

Ampang, Selangor, 68000, Malaysia

RECRUITING

Hospital Sultan Idris Shah Serdang

Kajang, Selangor, 43000, Malaysia

RECRUITING

Hospital Tengku Ampuan Rahimah

Klang, Selangor, 41200, Malaysia

RECRUITING

Hospital Selayang

Selayang Baru Utara, Selangor, 68100, Malaysia

RECRUITING

Hospital Melaka

Malacca, 75400, Malaysia

RECRUITING

MeSH Terms

Conditions

Bacteremia; Staphylococcal Infections

Interventions

Trimethoprim, Sulfamethoxazole Drug Combination; Clindamycin; Linezolid; Cloxacillin; Cefazolin; Vancomycin; Ceftaroline

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gram-Positive Bacterial Infections

Intervention Hierarchy (Ancestors)

Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Lincomycin; Lincosamides; Pyrrolidines; Glycosides; Carbohydrates; Acetamides; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Oxacillin; Penicillins; beta-Lactams; Lactams; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Cephalosporins; Thiazines; Glycopeptides; Glycoconjugates; Peptides; Amino Acids, Peptides, and Proteins

Central Study Contacts

Steven Lim, MBBS, MRCP

CONTACT

+60133620081; stevenlimcl@gmail.com

Josephine P Durai, MBBS

CONTACT

+6052085146; joeyukijo.28@gmai.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Infectious Diseases Physician

Study Record Dates

• First Submitted: March 22, 2024
• First Posted: March 29, 2024
• Study Start: June 28, 2024
• Primary Completion: May 1, 2025
• Study Completion: June 1, 2025
• Last Updated: July 5, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

MY (12)