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A Multi-centre Randomised Open-label Active Comparator-controlled Non-inferiority Trial Comparing Oral to Intravenous Antibiotics in the Early Management of Klebsiella Pneumoniae Liver Abscess
Sponsor study identifier
interventional
152
1 country
3
Study Start
November 5, 2013
Actual (reported)Primary Completion
January 16, 2018
Actual (reported)Study Completion
January 16, 2018
Actual (reported)Background: Klebsiella pneumoniae liver abscess is the most common etiology of liver abscess in Singapore and much of Asia, and its incidence is increasing. Current management includes prolonged intravenous antibiotic therapy, but there is limited evidence to guide oral conversion. The implicated K1/K2 capsule strain of Klebsiella pneumoniae is almost universally susceptible to ciprofloxacin, an antibiotic with high oral bioavailability. Our primary aim is to compare the efficacy of early (\<1 week) step-down to oral antibiotics, to continuing 4 weeks of intravenous antibiotics, in patients with Klebsiella liver abscess. Methods/Design: The study is designed as a multi-centre randomised open-label active comparator-controlled non-inferiority trial, with a non-inferiority margin of 12%. Eligible participants will be inpatients over the age of 21 with a CT or ultrasound scan suggestive of a liver abscess, and Klebsiella pneumoniae isolated from abscess fluid or blood. Randomisation into intervention or active control arms will be performed with a 1:1 allocation ratio. Participants randomised to the active control arm will receive IV ceftriaxone 2 grams daily to complete a total of 4 weeks of IV antibiotics. Participants randomised to the intervention arm will be immediately converted to oral ciprofloxacin 750mg twice daily. At week 4, all participants will have abdominal imaging and be assessed for clinical response (CRP \<20 mg/l, absence of fever, plus scan showing that the maximal diameter of the abscess has reduced). If criteria are met, antibiotics are stopped; if not, oral antibiotics are continued, with reassessment for clinical response fortnightly. If criteria for clinical response are met by week 12, the primary endpoint of clinical cure is met. A cost analysis will be performed to assess the cost saving of early conversion to oral antibiotics, and a quality-of-life analysis will be performed to assess if treatment with oral antibiotics is less burdensome than prolonged IV antibiotics. Discussion: Our results would help inform local and international practice guidelines regarding the optimal antibiotic management of Klebsiella liver abscess. A finding of non-inferiority may translate to the wider adoption of a more cost-effective strategy that reduces hospital length of stay and improves patient-centered outcomes and satisfaction.
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
January 16, 2018
Actual (reported)Click on a node to explore related trials.
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Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
October 22, 2012
Actual (reported)November 7, 2012
Actual (reported)November 5, 2013
Actual (reported)January 16, 2018
Actual (reported)January 16, 2018
Actual (reported)Clinical cure
The primary endpoint is "clinical cure", determined at Week 12 post-randomisation, and defined as CRP\< 20 mg/l, plus absence of documented fever ≥38°C in the preceding week, plus most recent abdominal imaging showing that the maximal diameter of the abscess has reduced.
Week 12
Clinical response
Week 4
all-cause mortality at any point between randomisation and week 12
Week 12
• unplanned readmission for any cause at any point between hospital discharge and week 12
Week 12
• unplanned need for drainage after enrolment at any point between randomisation and week 12 (the screening visit will document any plans for elective drainage)
Week 12
The intervention arm switched to oral antibiotics to complete 4 weeks of therapy. Oral antibiotics will be ciprofloxacin (or trimethoprim/sulfamethoxazole if the isolate is resistant).
The active comparator arm continues intravenous antibiotics to complete 4 weeks of therapy. Intravenous antibiotics will be ceftriaxone (or ertapenem if the isolate is resistant).
These entries preserve how the registry describes the intervention. Their treatment roles are shown separately from molecular identities.
Grouped treatment entry
Trimethoprim/sulfamethoxazole
The registry names several treatments. This does not confirm that participants received them together or that they form a single product.
View registry recordSingapore General Hospital
Singapore, 169856, Singapore
National University Hospital
Singapore, Singapore
Tan Tock Seng Hospital
Singapore, Singapore
Molton J, Phillips R, Gandhi M, Yoong J, Lye D, Tan TT, Fisher D, Archuleta S. Oral versus intravenous antibiotics for patients with Klebsiella pneumoniae liver abscess: study protocol for a randomized controlled trial. Trials. 2013 Oct 31;14:364. doi: 10.1186/1745-6215-14-364.
Yoong J, Yuen KH, Molton JS, Ding Y, Cher BP, Chan M, Kalimuddin S, Oon J, Young B, Low J, Salada BMA, Lee TH, Wijaya LM, Fisher D, Izharuddin E, Wei Y, Phillips R, Moorakonda R, Lye DC, Archuleta S. Cost-minimization analysis of oral versus intravenous antibiotic treatment for Klebsiella pneumoniae liver abscess. Sci Rep. 2023 Jun 16;13(1):9774. doi: 10.1038/s41598-023-36530-5.
Sophia Archuleta, MD
National University Hospital, Singapore
152 participants (actual enrollment reported by the registry).
First Submitted
October 22, 2012
First Posted
November 7, 2012
Study Start
November 5, 2013
Actual (reported)Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.
Contact the study team to confirm eligibility.
Molton JS, Chan M, Kalimuddin S, Oon J, Young BE, Low JG, Salada BMA, Lee TH, Wijaya L, Fisher DA, Izharuddin E, Koh TH, Teo JWP, Krishnan PU, Tan BP, Woon WWL, Ding Y, Wei Y, Phillips R, Moorakonda R, Yuen KH, Cher BP, Yoong J, Lye DC, Archuleta S. Oral vs Intravenous Antibiotics for Patients With Klebsiella pneumoniae Liver Abscess: A Randomized, Controlled Noninferiority Study. Clin Infect Dis. 2020 Aug 14;71(4):952-959. doi: 10.1093/cid/ciz881.
Primary Completion
January 16, 2018
Actual (reported)Study Completion
January 16, 2018
Actual (reported)Last Updated
August 27, 2018
Record last verified: 2018-08
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Source: ClinicalTrials.gov.
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