Clinical Trial: Antibiotics for Klebsiella Liver Abscess Study

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Multi-centre Randomised Open-label Active Comparator-controlled Non-inferiority Trial Comparing Oral to Intravenous Antibiotics in the Early Management of Klebsiella Pne

Brief Summary:

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-o

Detailed Summary:
Sponsor: National University Hospital, Singapore

Current Primary Outcome: Clinical cure [ Time Frame: Week 12 ]

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.


Original Primary Outcome: Clinical cure [ Time Frame: Week 10 ]

The primary outcome is clinical cure, determined at Week 10, and defined as CRP< 20 mg/l, plus absence of documented fever over 38°C in the preceding week.


Current Secondary Outcome: Clinical response [ Time Frame: Week 4 ]

The main secondary endpoint is "clinical response", determined at Week 4 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.


Original Secondary Outcome: Clinical response [ Time Frame: Week 4 ]

Clinical response, determined at week 4, and defined as CRP <20 mg/l, plus absence of documented fever over 38°C in the preceding week, plus 4 week abdominal imaging showing that the abscess is >50% smaller and no greater than 5cm.


Information By: National University Hospital, Singapore

Dates:
Date Received: October 22, 2012
Date Started: November 5, 2013
Date Completion: April 30, 2018
Last Updated: April 13, 2017
Last Verified: April 2017