Staphylococcus Aureus BacteremiaPhase 3EVOSNCT06336824
Early Intravenous to Oral Antibiotic Switch in Uncomplicated Staphylococcus Aureus Bacteraemia
A Phase 3 study testing Tab. Trimethoprim-sulfamethoxazole, Tab. Clindamycin, Tab. Cephalexin, or Tab. Linezolid and IV Cloxacillin, IV Cefazolin, IV Vancomycin, or IV Ceftaroline in people with Staphylococcus Aureus Bacteremia, run by Clinical Research Centre, Malaysia at 12 sites in Malaysia.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Staphylococcus Aureus Bacteremia
- What is being tested?
- Tab. Trimethoprim-sulfamethoxazole, Tab. Clindamycin, Tab. Cephalexin, or Tab. Linezolid and IV Cloxacillin, IV Cefazolin, IV Vancomycin, or IV Ceftaroline
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 290 participants
- Where
- 12 sitesMalaysia
- Study dates
- 28 Jun 2024to Jun 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 25Show fewer
- 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
- Severe liver disease (Child-Pugh class C)
- Severe immunodeficiency:
- HIV-positive patients with CD4<200 cells/uL or AIDS
- primary immunodeficiency disorders
- high-dose steroid therapy (>1 mg/kg prednisone or equivalent doses given for > 4 weeks or planned during intervention)
- immunosuppressive therapy
- neutropenia (<500 neutrophils/μl) at randomization or neutropenia expected during intervention phase due to immunosuppressive treatment
- solid organ or hematopoietic stem cell transplantation within the past 6 months or planned during treatment period
- 13.Short life expectancy < 3 months
- 14.Pregnancy (for women of childbearing potential)
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
Malaysia12 sites, 12 recruiting
- Recruiting
Hospital Sultanah Bahiyah
Alor Star, Kedah, 05460
Sharifah Baizura Syed Alwi, baizura1973@hotmail.my
- Recruiting
Hospital Ampang
Ampang, Selangor, 68000
Suraya Hanim Abdullah Hashim, surayahanim.abdullahhashim@gmail.com
- Recruiting
Hospital Pulau Pinang
George Town, Pulau Pinang, 10450
Chuan Huan Chuah, chchuah7@yahoo.com
- Recruiting
Hospital Raja Permaisuri Bainun
Ipoh, Perak, 30450
Steven Lim, stevenlimcl@gmail.com
- Recruiting
Hospital Sultanah Aminah
Johor Bahru, Johor, 80100
Wei Xuan Tuang, weixuan0706@gmail.com
- Recruiting
Hospital Sultan Idris Shah Serdang
Kajang, Selangor, 43000
Kah Chuan Lim, ck7902@gmail.com
- Recruiting
Hospital Tengku Ampuan Rahimah
Klang, Selangor, 41200
Azureen Azmel, aazmel@gmail.com
- Recruiting
Hospital Melaka
Malacca, 75400
Wee Fu Gan, ganweefu@gmail.com
- Recruiting
Hospital Seberang Jaya
Seberang Jaya, Pulau Pinang, 13700
Peng Peng Ang, angpp2209@gmail.com
- Recruiting
Hospital Selayang
Selayang Baru Utara, Selangor, 68100
Anuradha P. Radhakrisnan, anurapr70@gmail.com
- Recruiting
Hospital Tuanku Ja'afar
Seremban, Negeri Sembilan, 70300
Tiang Koi Ng, tiangkoi79@yahoo.com
- Recruiting
Hospital Sultan Abdul Halim
Sungai Petani, Kedah, 08000
Noralfazita An, noralfazitaa@moh.gov.my
About this study
Official title: Early Intravenous to Oral Antibiotic Switch in Uncomplicated Staphylococcus Aureus Bacteraemia: The EVOS Randomized Controlled Trial
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.
Read the detailed description
The study is conducted at 12 government tertiary hospitals with infectious diseases physicians in Malaysia. The study population comprises of 290 patients with uncomplicated SAB who have received 3 to 7 days of definitive IV antimicrobial therapy. Eligible participants are randomized 1:1 into 2 groups, early oral antibiotic switch versus standard IV antibiotic therapy, following the inclusion and exclusion criteria.
The study consists of 3 stages for each patient with a duration of approximately 12 weeks: screening and enrolment, open-label treatment with 7 to 11 days of study antibiotics, and follow-up until day 90 post-randomization. Phone call or inpatient follow up will be conducted at Day 7-11, Day 30, and Day 90 post- randomization to review patient's condition.
- Conditions
- Staphylococcus Aureus Bacteremia
- Being tested
- Tab. Trimethoprim-sulfamethoxazole, Tab. Clindamycin, Tab. Cephalexin, or Tab. Linezolid, IV Cloxacillin, IV Cefazolin, IV Vancomycin, or IV Ceftaroline
- Keywords
- bacteremia, oral antibiotics, Staphylococcus aureus
- Medical subject headings
- Bacteremia, Staphylococcal Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tab. Trimethoprim-sulfamethoxazole, Tab. Clindamycin, Tab. Cephalexin, or Tab. LinezolidDrug
Also called Bactrim, Dalacin, Ospexin, Zyvox
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.
IV Cloxacillin, IV Cefazolin, IV Vancomycin, or IV CeftarolineDrug
Also called Cloxacillin Sodium, Cefazolin Sandoz, Vancotex, Zinforo
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: IV Cloxacillin, IV Cefazolin, IV Vancomycin, or IV Ceftaroline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 90 days
Secondary outcomes (5)
Number of days of hospitalization
Number of calendar days of hospitalisation after the first positive blood culture for S. aureus.
Measured: 90 days
Rate of all-cause mortality
Any death occurred within 90 days of randomization.
Measured: 90 days
Rate of complications related to IV therapy
Any complications related to insertion or usage of peripheral branula or central catheter, and administration of IV drugs
Measured: 90 days
Rate of Clostridium difficile diarrhoea
A diagnosis of diarrhoea with ≥1 stool sample tested positive for C. difficile toxin or toxin gene.
Measured: 90 days
Rate of adverse events
Any untoward medical occurrence in a subject administered a medicinal product and which does not necessarily have a causal relationship with treatment.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2024
- Study start28 Jun 2024
- Primary completionMay 2025 (estimated)
- Study completionJun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Staphylococcus Aureus BacteremiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 290 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Clinical Research Centre, Malaysia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Steven Lim Chee Loon, Ministry of Health, Malaysia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06336824
- Sponsor's protocol ID
- EVOS 1.3 dated 12 March 2024
- Acronym
- EVOS
- Status last verified
- Jul 2024
- First submitted
- 22 Mar 2024
- Last updated
- 5 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Intravenous to Oral Antibiotic Switch in Uncomplicated Staphylococcus Aureus Bacteraemia: The EVOS Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06336824
- Acronym / sponsor ID
- EVOS / EVOS 1.3 dated 12 March 2024
- Conditions
- Staphylococcus Aureus Bacteremia
- Keywords
- bacteremia, oral antibiotics, Staphylococcus aureus
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 290 participants (estimated)
- Lead sponsor
- Clinical Research Centre, MalaysiaUniversity, hospital or other
- Study start
- 28 Jun 2024 (actual)
- Primary completion
- May 2025 (estimated)
- Study completion
- Jun 2025 (estimated)
- First posted
- 29 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The study is conducted at 12 government tertiary hospitals with infectious diseases physicians in Malaysia. The study population comprises of 290 patients with uncomplicated SAB who have received 3 to 7 days of definitive IV antimicrobial therapy. Eligible participants are randomized 1:1 into 2 groups, early oral antibiotic switch versus standard IV antibiotic therapy, following the inclusion and exclusion criteria.
The study consists of 3 stages for each patient with a duration of approximately 12 weeks: screening and enrolment, open-label treatment with 7 to 11 days of study antibiotics, and follow-up until day 90 post-randomization. Phone call or inpatient follow up will be conducted at Day 7-11, Day 30, and Day 90 post- randomization to review patient's condition.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early Oral Switch Therapy (EOS) | Experimental | Drug: Tab. Trimethoprim-sulfamethoxazole, Tab. Clindamycin, Tab. Cephalexin, or Tab. LinezolidPatients 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 |
| Standard IV therapy (SIV) | Active comparator | Drug: IV Cloxacillin, IV Cefazolin, IV Vancomycin, or IV CeftarolinePatients 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Blood culture positive for Staphylococcus aureus (S. aureus).
- Received 3 to 7 days of definitive IV antimicrobial therapy, defined as:
- 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.
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tab. Trimethoprim-sulfamethoxazole, Tab. Clindamycin, Tab. Cephalexin, or Tab. LinezolidAlso: Bactrim, Dalacin, Ospexin, ZyvoxThe 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. | Drug | Early Oral Switch Therapy (EOS) |
| IV Cloxacillin, IV Cefazolin, IV Vancomycin, or IV CeftarolineAlso: Cloxacillin Sodium, Cefazolin Sandoz, Vancotex, ZinforoThe 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. | Drug | Standard IV therapy (SIV) |
Primary outcome
Rate of SAB-relapse
Time frame: 90 days
defined as any new positive blood culture with S. aureus, and/or newly diagnosed metastatic S. aureus infection resulting from hematogenous dissemination
5 secondary outcomes
Number of days of hospitalization
Time frame: 90 days
Rate of all-cause mortality
Time frame: 90 days
Rate of complications related to IV therapy
Time frame: 90 days
Rate of Clostridium difficile diarrhoea
Time frame: 90 days
Rate of adverse events
Time frame: 30 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2024.
- Individual participant dataSharing planned: No
Related trials for Staphylococcus Aureus Bacteremia
RecruitingObservational study
Study of the Nasal Intracellular Reservoir of Staphylococcus Aureus in Patients With S. Aureus Bacteremia
Bacteria Infection Mechanism
RecruitingPhase 2
Combination Cefazolin With Ertapenem for Methicillin-susceptible Staphylococcus Aureus Bacteremia
Staphylococcus Aureus Bacteremia, Staphylococcus Aureus Septicemia
RecruitingPhase 4
Combination Antibiotic Therapy for Staphylococcus Aureus Bacteremia
Staphylococcus Aureus Bacteremia
RecruitingPhase 4
Dabigatran vs. Oral Anti-Xa Inhibitors in S. Aureus Bacteremia
Staphylococcus Aureus Endocarditis, Staphylococcus Aureus Septicemia
RecruitingPhase 4
Clopidogrel vs. Aspirin for Cardiovascular Risk Reduction in Patients With S. Aureus Bacteremia
Staphylococcus Aureus Endocarditis, Staphylococcus Aureus Septicemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tab. Trimethoprim-sulfamethoxazole, Tab. Clindamycin, Tab. Cephalexin, or Tab. Linezolid and IV Cloxacillin, IV Cefazolin, IV Vancomycin, or IV Ceftaroline in people with Staphylococcus Aureus Bacteremia, run by Clinical Research Centre, Malaysia at 12 sites in Malaysia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Malaysia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Steven Lim, MBBS, MRCP (+60133620081, stevenlimcl@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of SAB-relapse (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2024.