Comparison of continuing intravenous antibiotic therapy with switching to oral antibiotics in clinically stable patients with blood infections caused by Gram-negative bacteria (INVEST study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Tan Tock Seng Hospital Pte. Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

10 Dec 2025 → ongoing

Decision date (initial)

2025-11-10

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Singapore’s National Research Foundation Central Gap Fund

External identifiers

EU CT number

2024-517308-13-00

ClinicalTrials.gov

NCT05199324

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy, Pharmacoeconomic

To investigate if the early step-down to oral fluoroquinolones or trimethoprim-sulfamethoxazole will be clinically non-inferior to continuing IV antibiotic therapy in the primary outcome of 30-day all-cause mortality

Secondary objectives 1

1. To investigate if the early oral step-down therapy will result in significantly lower health resource/service utilisation and associated costs compared with continuing IV therapy.

Conditions and MedDRA coding

Gram-negative bacteraemia

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. ≥1 set of blood cultures positive for GNB associated with evidence of infection
2. Able to be randomised within 72 hours of index blood culture collection
3. Age ≥18 years (≥21 in Singapore)
4. Latest Pitt bacteraemia score <4
5. Patient or legal representative is able to provide informed consent

Exclusion criteria 15

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Compare the all-cause mortality at day 30 post-randomisation in patients from the standard arm versus intervention arm.

Secondary endpoints 10

1. Compare between standard and intervention arms: All-cause mortality at days 14 and 90 from the time of randomisation
2. Duration of survival from the time of randomisation until day 90
3. 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
4. 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
5. 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
6. 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
7. 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’)
8. Number of days alive and not in hospital (including OPAT) between the time of randomisation and day 90
9. 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.
10. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Tan Tock Seng Hospital Pte. Ltd.

Sponsor organisation

Tan Tock Seng Hospital Pte. Ltd.

Address

11 Jalan Tan Tock Seng

City

Singapore

Postcode

308433

Country

Singapore

Scientific contact point

Organisation

Tan Tock Seng Hospital Pte. Ltd.

Contact name

Prof David Lye

Public contact point

Organisation

Tan Tock Seng Hospital Pte. Ltd.

Contact name

Prof David Lye

Third parties 2

Locations

3 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 30 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications