Oritavancin for Treatment of Serious Cardiac Infections (OSCAR)

A Multicentre Phase II Prospective Pilot Study of Pharmacokinetic- and TDM-guided Oritavancin Dosing Strategies for the Management of Gram-positive Cardiac Infections (the OSCAR Study)

Cardiac infections, including infective endocarditis and cardiovascular implantable electronic device infections, are associated with substantial morbidity and mortality and are commonly caused by gram-positive bacteria. Standard management typically requires prolonged courses of intravenous antibiotics and extended hospitalisation, which are costly, burdensome, and associated with complications related to long-term vascular access. People who inject drugs are disproportionately affected and often experience stigma, barriers to care, and poorer outcomes. Long-acting lipoglycopeptides such as oritavancin maintain therapeutic serum concentrations for prolonged periods and may offer an alternative to conventional intravenous antibiotic regimens. Oritavancin is not TGA-registered in Australia and is accessed as an unregistered medicine (for example, via SAS or clinical trials). It is approved in other jurisdictions, including the United States and European Union, for acute bacterial skin and skin structure infections. Prospective data in cardiac infections remain limited, and optimal dosing strategies, including the role of therapeutic drug monitoring, are uncertain. This multicentre, open-label pilot study will assess the feasibility, pharmacokinetics, safety, acceptability, and preliminary efficacy of oritavancin for gram-positive cardiac infections using both standard fixed dosing and TDM-guided dosing strategies. Findings will inform PK/PD modelling, the potential role of TDM, and the design of future larger-scale trials and models of care, including alternatives to prolonged inpatient intravenous therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Infective Endocarditis; Gram-positive Bacterial Infections; Cardiac Device Infection
• Intervention / Treatment: Drug: Oritavancin; Drug: Oritavancin

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hila Haskelberg; Phone Number: 61293850900; Email: hhaskelberg@kirby.unsw.edu.au

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Sydney, New South Wales, Australia, 2010
      • St Vincent's Hospital
      • Principal Investigator: David Goodman
    • Sydney, New South Wales, Australia, 2031
      • Prince of Wales Hospital
      • Principal Investigator: Marianne Martinello

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years
2. Hospitalised for management of a cardiac infection (infective endocarditis or cardiovascular implantable electronic device infections)
3. Gram-positive organism identified in blood or tissue culture, that in the opinion of the investigator is the cause of cardiac infection and would be treatable with a finite antibiotic duration (e.g., 4-6 weeks)
4. Afebrile for at least 24 hours at screening
5. Clearance of blood cultures for at least 24 hours at screening
6. Receiving effective antibiotic therapy for at least 24 hours and no more than 14 days at screening
7. Willingness of both treating provider and participant to proceed with oritavancin therapy
8. Able to provide written informed consent
9. Willingness and ability to participate in study procedures, including follow-up visits and drug monitoring

Exclusion Criteria:

1. History of severe allergic reaction or hypersensitivity to oritavancin or any of its components
2. Severe renal impairment (eGFR < 30 mL/min/1.73 m²) or currently receiving dialysis
3. Severe hepatic impairment (Child-Pugh class C)
4. Current infection involving the central nervous system, including septic emboli, ischemic or haemorrhagic stroke, epidural abscess, or meningitis (excluding prior/unrelated central nervous system events).
5. Presence of prosthetic heart valve
6. Culture negative endocarditis
7. Presence of any other active infection requiring concurrent antibiotic treatment that could interfere with study outcomes
8. Infection with Gram positive organism not susceptible to oritavancin or vancomycin (vancomycin MIC > 2 μg/mL).
9. Use of contraindicated medications (see Section 8)
10. Participation in another interventional clinical trial that may confound study outcomes
11. Pregnant or breastfeeding people, or those planning to become pregnant during the study period (people of childbearing potential must have a negative pregnancy test during hospitalization and use effective contraception for trial duration and for 3 months after last infusion of study medication).
12. Immunosuppression (defined as active chemotherapy expected to cause absolute neutrophil count <100 cells/mm3 lasting >7 days during the study period, bone marrow transplantation in the preceding 90 days, solid organ transplantation within prior 3 months or receipt of augmented immunosuppression for rejection within 3 months, chronic granulomatous disease, HIV with a CD4 count <50 cells/mm3 based on last known measure).
13. Any condition (e.g. severe cognitive impairment, psychiatric illness, active withdrawal) that, in the opinion of the investigator, would limit the participant's ability to comply with study procedures or give informed consent
14. Medically unstable in opinion of treating clinician that would preclude participation
15. Cases in which the investigator deem curative or finite antibiotic treatment unlikely (e.g., long term indefinite suppressive antibiotics are likely such as retained hardware).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A1: Oritavancin, guideline-based dosing; Participants will receive oritavancin intravenously using a fixed weekly dosing schedule consistent with contemporary guideline-based practice. Intensive pharmacokinetic sampling will be performed to develop a population pharmacokinetic model	Drug: Oritavancin; Oritavancin administered by intravenous infusion using a fixed weekly dosing schedule consistent with the protocol-defined guideline-based regimen (1.2 g IV once weekly); Drug: Oritavancin; Participants will receive an initial oritavancin dose (e.g. 1.2 g IV), with subsequent dosing intervals and/or additional doses informed by pre-specified TDM algorithms and individual PK estimates derived from the population model developed in Group B1.
Experimental: Cohort A2: Oritavancin (TDM-guided dosing); Participants will receive oritavancin intravenously with subsequent dosing intervals and/or additional doses guided by therapeutic drug monitoring and individual pharmacokinetic estimates derived from the population pharmacokinetic model developed in Cohort A1	Drug: Oritavancin; Oritavancin administered by intravenous infusion using a fixed weekly dosing schedule consistent with the protocol-defined guideline-based regimen (1.2 g IV once weekly); Drug: Oritavancin; Participants will receive an initial oritavancin dose (e.g. 1.2 g IV), with subsequent dosing intervals and/or additional doses informed by pre-specified TDM algorithms and individual PK estimates derived from the population model developed in Group B1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Desirability of Outcome Ranking (DOOR) at Day 70	Composite ordinal outcome adapted for Gram-positive cardiac infections. Participants will be ranked from most to least desirable outcome as follows: = alive with no clinical failure, infectious complication, or serious adverse event/adverse event leading to study drug discontinuation;; = alive with 1 of these events;; = alive with 2 of these events;; = alive with all 3 of these events;; = death. Within each rank, ties will be resolved using net change in EQ-5D score from baseline to Day 70, with greater improvement indicating a more desirable outcome.	Day 70 post-enrolment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total oritavancin plasma concentration at scheduled sampling time points	Observed total oritavancin plasma concentrations measured at protocol-specified sampling time points to support development of the population pharmacokinetic model.	From post-dose Day 1 through Day 70 post-enrolment
Oritavancin dosing interval achieved in the therapeutic drug monitoring-guided cohort	Time interval in days between consecutive oritavancin doses in participants managed using therapeutic drug monitoring-guided dosing.	From Day 1 to Day 70 post-enrolment
Number of participants with treatment-emergent adverse events in the oritavancin cohorts	Number of participants receiving oritavancin with at least 1 treatment-emergent adverse event.	From enrolment to Day 180 post-enrolment
Number of participants with serious adverse events in the oritavancin cohorts	Number of participants receiving oritavancin with at least 1 serious adverse event.	From enrolment to Day 180 post-enrolment
Number of participants with infusion-related reactions in the oritavancin cohorts	Number of participants receiving oritavancin with at least 1 infusion-related reaction.	From enrolment to Day 180 post-enrolment
Proportion of participants completing protocol-specified dosing and monitoring through Day 70	Proportion of participants who complete the protocol-specified dosing schedule and planned therapeutic drug monitoring/sample collection through Day 70.	From enrolment to Day 70 post-enrolment
Recruitment rate	Proportion of eligible participants who are enrolled into the study.	From study opening to completion of enrolment
Retention rate at Day 70	Proportion of enrolled participants who complete Day 70 follow-up.	From enrolment to Day 70 post-enrolment
Number of participants who complete planned study treatment	Number of participants who complete their planned study treatment course as determined by the treating clinician and protocol-defined study treatment period.	By Day 70 post-enrolment
Number of participants with clinical or microbiological failure	Number of participants with clinical or microbiological failure, including worsening or recurrent signs of cardiac infection, need for change/addition of antibiotic therapy due to inadequate response, or relapse with the same organism following study treatment.	By Day 70 post-enrolment
Number of participants with hospital readmission by Day 70	Number of participants with at least 1 hospital readmission.	By Day 70 post-enrolment
Number of participants who die by Day 70	All-cause mortality.	By Day 70 post-enrolment
Number of participants with hospital readmission by Day 180	Number of participants with at least 1 hospital readmission.	By Day 180 post-enrolment
Number of participants who die by Day 180	All-cause mortality.	By Day 180 post-enrolment
Change from Baseline to Day 70 in EuroQol 5-Dimension 5-Level Index Score	Health-related quality of life will be assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L). The EQ-5D-5L index score is derived from participant responses across five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Using the Australian EQ-5D-5L value set, possible index scores range from -0.30 to 1.00, where 1.00 represents full health, 0 represents a health state equivalent to death, and scores below 0 represent health states valued worse than death. Higher scores indicate better health-related quality of life. Change will be calculated as the Day 70 score minus the baseline score; a positive change indicates improvement.	Baseline to Day 70 post-enrolment

Collaborators and Investigators

• Sponsor: Kirby Institute
• Investigators: Principal Investigator: Gail Matthews, MBChB MRCP(UK) FRACP PhD FAAHM, Kirby Institute

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: March 26, 2026
• First Submitted That Met QC Criteria: April 19, 2026
• First Posted (Actual): April 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Therapeutic drug monitoring; Infective endocarditis; Oritavancin; Long-acting antibiotic; Lipoglycopeptide; Cardiac device infection; Gram-positive infection
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Endocarditis; Gram-Positive Bacterial Infections; oritavancin
• Other Study ID Numbers: OSCAR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No