An interventional study of Resistance-Optimised Precision Dosing and Standard Care Dosing in Hospital-acquired Pneumonia (HAP), Ventilator-Associated Pneumonia (VAP) and Nosocomial Respiratory Infection, sponsored by The University of Queensland. Not yet recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-15.
Sponsored by The University of Queensland · Not applicable, Interventional, and Treatment
Critically ill people who need a breathing machine often develop hospital-acquired lung infections. These infections are commonly treated with the antibiotics piperacillin/tazobactam or meropenem. However, standard antibiotic doses may not always provide the right drug levels to fully treat the infection or help prevent antibiotic resistance.
The purpose of this study is to determine whether a resistance-optimized antibiotic dosing approach improves recovery compared with standard antibiotic dosing in critically ill adults with hospital-acquired respiratory infections.
Participants will be randomly assigned to 1 of 2 groups:
Resistance-optimized precision dosing - guided by therapeutic drug monitoring and dosing software.
Standard care - antibiotic dosing used at the participating hospital.
All participants will receive treatment with either piperacillin/tazobactam or meropenem as determined by their treating clinical team. The study will compare whether the precision dosing approach leads to better clinical recovery, reduces the development of antibiotic-resistant bacteria, and is safe for participants.
Approximately 610 mechanically ventilated adults will be enrolled from intensive care units in multiple countries. Participants will be followed for up to 28 days after starting study antibiotic treatment.
Critically ill adults who require mechanical ventilation commonly develop hospital-acquired respiratory infections. These infections are frequently treated with the beta-lactam antibiotics piperacillin/tazobactam or meropenem. Standard antibiotic dosing may not always achieve drug levels that provide the best balance between treating infection and reducing the development of antibiotic resistance.
The Resistance-Optimised Antimicrobial Dosing in Critically Ill Patients Randomized Controlled Trial (ROAD-RCT) is a multicentre, international, investigator-initiated, open-label, randomized, parallel-group superiority trial. The study aims to determine whether resistance-optimised precision dosing improves clinical cure compared with standard care dosing in mechanically ventilated critically ill adults with hospital-acquired respiratory infections.
A total of approximately 610 participants will be enrolled and randomized in a 1:1 ratio to one of two treatment strategies:
Resistance-optimised precision dosing guided by model-informed precision dosing (MIPD).
Standard care antibiotic dosing according to local clinical practice.
Participants will receive treatment with either piperacillin/tazobactam or meropenem as prescribed by their treating clinical team. In the intervention group, dosing recommendations will be supported by therapeutic drug monitoring (TDM), patient clinical information, and dosing software to help achieve antibiotic exposure targets associated with suppression of antimicrobial resistance while remaining within accepted safety limits. Participants assigned to standard care will receive antibiotic dosing determined by their treating clinicians.
The primary outcome is clinical cure at Day 14 after initiation of study antibiotic therapy.
Secondary outcomes include time to clinical cure, mortality, treatment-related adverse events, duration of organ support therapies, emergence of antibiotic resistance, acquisition of new resistant microorganisms, hospital and intensive care unit length of stay, quality of life, and health-economic outcomes.
Participants will be followed for up to 28 days after initiation of study antibiotic treatment.
The study hypothesis is that resistance-optimised precision dosing will improve clinical cure while reducing the emergence of antimicrobial resistance compared with standard care dosing.
The results of this study will provide evidence about the effectiveness, safety, feasibility, and potential scalability of precision antibiotic dosing strategies in critically ill patients with hospital-acquired respiratory infections.
The patient is diagnosed with a probable or definitive respiratory infection and exhibits at least one of the following clinical features:
I. New onset or worsening pulmonary symptoms or signs: increase in volume and/or purulence of respiratory secretions, worsening of hypoxaemia requiring an increase in the FiO2 and/or need for acute changes in the ventilator support system to support oxygenation.
II. Radiological findings deemed consistent with a respiratory infection. III. Clinical signs and symptoms of infection: fever > 38 °C, leucocytosis, increase in acute phase reactants such as C-reactive protein or procalcitonin.
Exclusion Criteria:
Participants will receive piperacillin/tazobactam or meropenem using resistance-optimised precision dosing guided by model-informed precision dosing (MIPD). Dosing recommendations will be based on patient clinical characteristics and therapeutic drug monitoring results to achieve predefined antibiotic exposure targets associated with suppression of antimicrobial resistance. Dosing will be reviewed and adjusted throughout treatment according to MIPD recommendations until cessation of study antibiotic therapy, intensive care unit discharge, or Day 14, whichever occurs first.
Behavioral: Resistance-Optimised Precision Dosing
Participants will receive piperacillin/tazobactam or meropenem dosed according to routine clinical practice at the participating site. The initial choice of antibiotic, dose, infusion duration, dosing interval, and any subsequent dose adjustments will be determined by the treating clinical team in accordance with local standard care. Therapeutic drug monitoring may be performed if it is part of routine clinical practice at the study site. Treatment will continue until antibiotic cessation, intensive care unit discharge, or Day 14 after initiation of study antibiotic therapy, whichever occurs first.
Behavioral: Standard Care Dosing
Participants assigned to the intervention group will receive piperacillin/tazobactam or meropenem using resistance-optimised precision dosing guided by model-informed precision dosing (MIPD). Dosing recommendations will be based on patient clinical characteristics and therapeutic drug monitoring results and are intended to achieve antibiotic exposure targets associated with suppression of antimicrobial resistance while remaining within established safety limits. Dosing will be reviewed and adjusted during treatment using MIPD recommendations.
Participants assigned to the standard care group will receive piperacillin/tazobactam or meropenem according to routine clinical practice at the participating site. Antibiotic dose, infusion duration, dosing interval, and dose adjustments will be determined by the treating clinical team. Therapeutic drug monitoring may be performed if it is part of usual care at the study site.
Clinical cure
Clinical cure at Day 14 following initiation of study beta-lactam antimicrobial therapy. Clinical cure is defined as completion of the antimicrobial treatment course without recommencement of antimicrobial therapy for the same infectious episode within 48 hours of cessation, cessation of therapy not being due to palliative care, and survival for at least 48 hours after completion of the antimicrobial course.
Time frame: Day 14
Time to Clinical Cure
Time in hours from initiation of study antibiotic therapy to clinical cure.
Time frame: Up to Day 14
All-cause mortality
Any death documented within time frame
Time frame: 28 days
Emergence of antibiotic resistance
Antibiotic resistance emergence is defined as any of the following: emergence of resistance to beta-lactam antimicrobials in the index microorganism from the surveillance and/or clinical samples; acquisition of (a) new beta-lactam antimicrobials-resistant microorganism(s) in the surveillance and/or clinical samples, or the detection of new antimicrobial resistance gene classes (whole genome sequencing and metagenomic evaluation) in the surveillance and/or clinical samples.
Time frame: Day 14
Incremental Cost-Utility Ratio
Incremental Cost-Utility Ratio incorporating the Quality adjusted life years based on the EQ-5D-5L questionnaire, with costs converted using purchasing power parity.
Time frame: Day 28
Treatment emergent adverse events
Any adverse event attributed to the study drug per protocol definitions.
Time frame: Day 14
C. difficile diarrhoea
Diagnosis of C. difficile diarrhoea
Time frame: Day 14
Duration of artificial organ support
Duration of mechanical ventilation, renal replacement therapy, extracorporeal membrane oxygenation, and duration of vasopressor therapy.
Time frame: Day 14
Intensive Care Unit Length of Stay
Duration of ICU admission
Time frame: Day 28
No study locations are listed for this record.
Documents are hosted by the registry — open the source record to download them.
Plan to share: Undecided
This study is not yet recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Healthcare-Associated Pneumonia→
The University of Queensland