Please use this identifier to cite or link to this item: https://doi.org/10.1186/s13063-022-06495-3
Title: Early oral stepdown antibiotic therapy versus continuing intravenous therapy for uncomplicated Gram-negative bacteraemia (the INVEST trial): study protocol for a multicentre, randomised controlled, open-label, phase III, non-inferiority trial
Authors: Lee, I Russel 
Tong, Steven YC
Davis, Joshua S
Paterson, David L
Syed-Omar, Sharifah F
Peck, Kwong Ran
Chung, Doo Ryeon
Cooke, Graham S
Libau, Eshele Anak 
Rahman, Siti-Nabilah BA 
Gandhi, Mihir P 
Shi, Luming 
Zheng, Shuwei 
Chaung, Jenna
Tan, Seow Yen
Kalimuddin, Shirin 
Archuleta, Sophia 
Lye, David C 
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
Gram-negative bacteraemia
Antibiotics
Early oral stepdown therapy
Oral fluoroquinolones
Oral trimethoprim-sulfamethoxazole
Health economic evaluation
Quality of life
CIPROFLOXACIN
INFECTION
Issue Date: 19-Jul-2022
Publisher: BMC
Citation: Lee, I Russel, Tong, Steven YC, Davis, Joshua S, Paterson, David L, Syed-Omar, Sharifah F, Peck, Kwong Ran, Chung, Doo Ryeon, Cooke, Graham S, Libau, Eshele Anak, Rahman, Siti-Nabilah BA, Gandhi, Mihir P, Shi, Luming, Zheng, Shuwei, Chaung, Jenna, Tan, Seow Yen, Kalimuddin, Shirin, Archuleta, Sophia, Lye, David C (2022-07-19). Early oral stepdown antibiotic therapy versus continuing intravenous therapy for uncomplicated Gram-negative bacteraemia (the INVEST trial): study protocol for a multicentre, randomised controlled, open-label, phase III, non-inferiority trial. TRIALS 23 (1). ScholarBank@NUS Repository. https://doi.org/10.1186/s13063-022-06495-3
Abstract: Background: The incidence of Gram-negative bacteraemia is rising globally and remains a major cause of morbidity and mortality. The majority of patients with Gram-negative bacteraemia initially receive intravenous (IV) antibiotic therapy. However, it remains unclear whether patients can step down to oral antibiotics after appropriate clinical response has been observed without compromising outcomes. Compared with IV therapy, oral therapy eliminates the risk of catheter-associated adverse events, enhances patient quality of life and reduces healthcare costs. As current management of Gram-negative bacteraemia entails a duration of IV therapy with limited evidence to guide oral conversion, we aim to evaluate the clinical efficacy and economic impact of early stepdown to oral antibiotics. Methods: This is an international, multicentre, randomised controlled, open-label, phase III, non-inferiority trial. To be eligible, adult participants must be clinically stable / non-critically ill inpatients with uncomplicated Gram-negative bacteraemia. Randomisation to the intervention or standard arms will be performed with 1:1 allocation ratio. Participants randomised to the intervention arm (within 72 h from index blood culture collection) will be immediately switched to an oral fluoroquinolone or trimethoprim-sulfamethoxazole. Participants randomised to the standard arm will continue to receive IV therapy for at least 24 h post-randomisation before clinical re-assessment and decision-making by the treating doctor. The recommended treatment duration is 7 days of active antibiotics (including empiric therapy), although treatment regimen may be longer than 7 days if clinically indicated. Primary outcome is 30-day all-cause mortality, and the key secondary outcome is health economic evaluation, including estimation of total healthcare cost as well as assessment of patient quality of life and number of quality-adjusted life years saved. Assuming a 30-day mortality of 8% in the standard and intervention arms, with 6% non-inferiority margin, the target sample size is 720 participants which provides 80% power with a one-sided 0.025 α-level after adjustment for 5% drop-out. Discussion: A finding of non-inferiority in efficacy of oral fluoroquinolones or trimethoprim-sulfamethoxazole versus IV standard of care antibiotics may hypothetically translate to wider adoption of a more cost-effective treatment strategy with better quality of life outcomes. Trial registration: ClinicalTrials.govNCT05199324. Registered 20 January 2022.
Source Title: TRIALS
URI: https://scholarbank.nus.edu.sg/handle/10635/230397
ISSN: 1745-6215
1745-6215
DOI: 10.1186/s13063-022-06495-3
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
Early oral stepdown antibiotic therapy versus continuing intravenous therapy for uncomplicated Gram-negative bacteraemia (th.pdfPublished version1.13 MBAdobe PDF

OPEN

NoneView/Download

Page view(s)

33
checked on Sep 15, 2022

Download(s)

2
checked on Sep 15, 2022

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.