Oritavancin for Treatment of Serious Cardiac Infections

NCT07550595 | Not Yet Recruiting Phase 2

• 1 other identifier: OSCAR
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Infective Endocarditis; Cardiac Device Infection; Gram-positive Bacterial Infections

Keywords

Oritavancin; Long-acting antibiotic; Lipoglycopeptide; Infective endocarditis; Cardiac device infection; Gram-positive infection; Therapeutic drug monitoring; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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: 1. = alive with no clinical failure, infectious complication, or serious adverse event/adverse event leading to study drug discontinuation; 2. = alive with 1 of these events; 3. = alive with 2 of these events; 4. = alive with all 3 of these events; 5. = 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 Outcomes (15)

• Total oritavancin plasma concentration at scheduled sampling time points

  From post-dose Day 1 through Day 70 post-enrolment

• Oritavancin dosing interval achieved in the therapeutic drug monitoring-guided cohort

  From Day 1 to Day 70 post-enrolment

• Number of participants with treatment-emergent adverse events in the oritavancin cohorts

  From enrolment to Day 180 post-enrolment

• Number of participants with serious adverse events in the oritavancin cohorts

  From enrolment to Day 180 post-enrolment

• Number of participants with infusion-related reactions in the oritavancin cohorts

  From enrolment to Day 180 post-enrolment

Study Arms (2)

Cohort A1: Oritavancin, guideline-based dosing

EXPERIMENTAL

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

Cohort A2: Oritavancin (TDM-guided dosing)

EXPERIMENTAL

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

Interventions

Oritavancin DRUG

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)

Cohort A1: Oritavancin, guideline-based dosing

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Hospitalised for management of a cardiac infection (infective endocarditis or cardiovascular implantable electronic device infections)
• 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)
• Afebrile for at least 24 hours at screening
• Clearance of blood cultures for at least 24 hours at screening
• Receiving effective antibiotic therapy for at least 24 hours and no more than 14 days at screening
• Willingness of both treating provider and participant to proceed with oritavancin therapy
• Able to provide written informed consent
• Willingness and ability to participate in study procedures, including follow-up visits and drug monitoring

You may not qualify if:

• History of severe allergic reaction or hypersensitivity to oritavancin or any of its components
• Severe renal impairment (eGFR \< 30 mL/min/1.73 m²) or currently receiving dialysis
• Severe hepatic impairment (Child-Pugh class C)
• 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).
• Presence of prosthetic heart valve
• Culture negative endocarditis
• Presence of any other active infection requiring concurrent antibiotic treatment that could interfere with study outcomes
• Infection with Gram positive organism not susceptible to oritavancin or vancomycin (vancomycin MIC \> 2 μg/mL).
• Use of contraindicated medications (see Section 8)
• Participation in another interventional clinical trial that may confound study outcomes
• 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).
• 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).
• 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
• Medically unstable in opinion of treating clinician that would preclude participation
• 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).

Sponsors & Collaborators

• Kirby Institute: lead

Study Sites (3)

St Vincent's Hospital

Sydney, New South Wales, 2010, Australia

Location

Prince of Wales Hospital

Sydney, New South Wales, 2031, Australia

Location

Royal Prince Alfred Hospital

Sydney, New South Wales, 2050, Australia

Location

MeSH Terms

Conditions

Endocarditis; Gram-Positive Bacterial Infections

Interventions

oritavancin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Gail Matthews, MBChB MRCP(UK) FRACP PhD FAAHM

  Kirby Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hila Haskelberg

CONTACT

61293850900; hhaskelberg@kirby.unsw.edu.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2026
• First Posted: April 24, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3)