Resistance-Optimised Antimicrobial Dosing in Critically Ill Patients, a Randomised Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 610
- 主要终点
- Clinical cure
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient is ≥ 18 years of age.
- •The patient has been admitted to the hospital for ≥ 48 h or was discharged from a hospital within the preceding seven days and is currently admitted to the ICU.
- •The patient is intubated and mechanically ventilated.
- •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.
- •The patient has been commenced on empiric or targeted treatment with piperacillin/tazobactam or meropenem for the management of a respiratory infection, with an expected duration of treatment of > 72 h.
- •Piperacillin/tazobactam or meropenem have been commenced in an ICU that participates in ROAD-RCT.
- •The patient has an appropriate arterial or venous access for blood sampling.
排除标准
- •The patient is known or suspected to be pregnant.
- •The patient has a known allergy to piperacillin/tazobactam or meropenem.
- •The patient has a community-acquired respiratory infection or chemical pneumonitis in the context of bronchoaspiration.
- •The patient has received piperacillin/tazobactam or meropenem for more than 48 h.
- •The antimicrobial dose initiated empirically is > 4 g daily for meropenem and > 18 g daily (16 g piperacillin / 2 g tazobactam) for piperacillin/tazobactam (excluding the loading dose) in patients who are not receiving renal replacement therapy.
- •The antimicrobial dose initiated empirically is > 18 g daily (16 g piperacillin / 2 g tazobactam) for piperacillin/tazobactam and > 2 g daily for meropenem in patients receiving renal replacement therapy (Table 1).
- •The patient's death is deemed imminent and inevitable.
- •The patient has previously been enrolled in ROAD-RCT.
- •The patient is or has been enrolled in another antimicrobial clinical trial that may interfere with the intervention as determined by the study investigators.
- •The patient has a baseline (at ICU admission or enrolment) positive rectal and/or nasopharyngeal screening swab, or is known to have been colonised within the past 6 months, with any of the following beta-lactam-resistant Gram-negative microorganism(s): carbapenem-resistant Enterobacterales, P. aeruginosa with DTR or carbapenem-resistant A. baumannii complex.
- •There is a prior known or likely reason that the patient would not consent if they were able to be asked.
研究组 & 干预措施
Arm 1: Resistance-Optimised Precision Dosing
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.
干预措施: Resistance-Optimised Precision Dosing (Behavioral)
Arm 2: Standard Care 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.
干预措施: Standard Care Dosing (Behavioral)
结局指标
主要结局
Clinical cure
时间窗: Day 14
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.
次要结局
- Time to Clinical Cure(Up to Day 14)
- All-cause mortality(28 days)
- Emergence of antibiotic resistance(Day 14)
- Incremental Cost-Utility Ratio(Day 28)
- Treatment emergent adverse events(Day 14)
- C. difficile diarrhoea(Day 14)
- Duration of artificial organ support(Day 14)
- Intensive Care Unit Length of Stay(Day 28)