bromhexine hydrochloride, sulfamethoxazole, trimethoprim for Gram-negative bacteraemia

Inclusion criteria

• {"criterion_text":"- ≥1 set of blood cultures positive for GNB associated with evidence of infection\n- Able to be randomised within 72 hours of index blood culture collection\n- Age ≥18 years (≥21 in Singapore)\n- Latest Pitt bacteraemia score <4\n- Patient or legal representative is able to provide informed consent"}

Exclusion criteria

• {"criterion_text":"- Established uncontrolled focus of infection (e.g. undrained abdominal abscess)\n- Severely immunocompromised\n- Women who are known to be pregnant or breast-feeding\n- Treatment is not with intent to cure the infection (i.e. palliative care)\n- Unable to collect patient’s follow-up data for at least 30 days post-randomisation\n- Treating doctor deems enrolment into trial is not in the best interest of the patient\n- Previous enrolment in this trial\n- Complicated infections (e.g. necrotising fasciitis)\n- Septic shock\n- Polymicrobial bacteraemia\n- Bacteraemia due to vascular catheter or intravascular materials that cannot be removed\n- Specific Gram-negative pathogens that cannot be effectively treated with fluoroquinolones or trimethoprim-sulfamethoxazole (e.g. Burkholderia, Brucella)\n- Index GNB with resistance to fluoroquinolones AND trimethoprim-sulfamethoxazole\n- Hypersensitivity to fluoroquinolones AND sulpha drugs\n- Unable to consume or absorb oral medications for any reason or unsuitable for ongoing IV therapy (e.g. no intravenous access)"}

Primary endpoints

• {"endpoint_text":"- Compare the all-cause mortality at day 30 post-randomisation in patients from the standard arm versus intervention arm.","definition_or_measurement_approach":"All-cause mortality at day 30 post-randomisation compared between the standard (continuing IV therapy) and intervention (early oral step-down) arms; measured as death from any cause within 30 days of randomisation."}

Secondary endpoints

• {"endpoint_text":"- Compare between standard and intervention arms: All-cause mortality at days 14 and 90 from the time of randomisation\n- Duration of survival from the time of randomisation until day 90\n- Number of days on IV antibiotic therapy in the total index hospitalisation (including outpatient parenteral antibiotic therapy [OPAT]) for surviving participants from the time of randomisation until i. hospital discharge and ii. day 90\n- Number of days alive and free of antibiotics (i. for all antibiotics and ii. for IV antibiotics) between the time of randomisation and day 90\n- Adverse events from the time of randomisation until day 90 including: C. difficile-associated diarrhoea Peripherally inserted central catheter and other central venous catheter complications requiring line removal during index hospitalisation from the time of randomisation Liver function test abnormalities or kidney injury\n- Change in treatment strategy (e.g. switch to IV antibiotics from allocated oral antibiotics or vice versa) between the time of randomisation and day 30 due to: An adverse event deemed by the treating doctor to be of sufficient severity to change treatment strategy Presumed lack of efficacy of treatment strategy according to the judgement of treating doctor\n- Time to being discharged alive from the total index hospitalisation (including OPAT and hospital in the home) between the time of randomisation and day 90 (note: any death occurrence within 90 days will be considered ‘90 days’)\n- Number of days alive and not in hospital (including OPAT) between the time of randomisation and day 90\n- Readmission or extended hospitalisation by day 90. Readmission is defined as a new hospitalisation for any cause or a return to ambulatory hospital services occurring after discharge from the index hospitalisation. Extended hospitalisation is defined as >14 days of hospital LOS starting from the day of randomisation.\n- Health economic evaluation, including estimation of total healthcare cost (from healthcare system and patient perspective)* and assessment of patient’s quality of life via EQ-5D by day 90 *Cost savings/effectiveness analyses will be performed in selected hospital sites","definition_or_measurement_approach":"Each secondary endpoint is measured as specified: all-cause mortality at days 14 and 90; survival time to day 90; days on IV antibiotics during index hospitalisation (including OPAT) to discharge and to day 90; days alive and antibiotic-free to day 90; adverse events recorded from randomisation to day 90 including specified events; changes in treatment strategy to day 30 due to defined reasons; time to discharge alive to day 90 (deaths counted as 90 days); days alive and not hospitalised to day 90; readmission or extended hospitalisation (defined as >14 days LOS) to day 90; and health economic evaluation including healthcare costs and EQ-5D quality-of-life assessment to day 90, with cost-effectiveness analyses at selected sites."}

Spain

Earliest CTIS Part Ii Submission Date

14-04-2025

Latest Decision Or Authorization Date

29-07-2025

Processing Time Days

106

Number Of Sites

1

Number Of Participants

30

Italy

Earliest CTIS Part Ii Submission Date

31-01-2025

Latest Decision Or Authorization Date

10-11-2025

Processing Time Days

283

Number Of Sites

4

Number Of Participants

120

Greece

Earliest CTIS Part Ii Submission Date

03-10-2025

Latest Decision Or Authorization Date

17-03-2026

Processing Time Days

165

Number Of Sites

1

Number Of Participants

10

Primary sponsor

Full Name

Tan Tock Seng Hospital Pte. Ltd.

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Singapore

Third parties

• {"country":"Greece","full_name":"Coronis Research S.A.","duties_or_roles":["1","5"],"organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Consorzio Per Valutazioni Biologiche E Farmacologiche","duties_or_roles":["1","12","5","8"],"organisation_type":"Pharmaceutical company"}