Liver Abscess, PyogenicPhase 4NCT01723150
Antibiotics for Klebsiella Liver Abscess Study
A Phase 4 study testing Ciprofloxacin, Ceftriaxone and Trimethoprim/sulfamethoxazole in people with Liver Abscess, Pyogenic, run by National University Hospital, Singapore at 3 sites in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Liver Abscess, Pyogenic
- What is being tested?
- Ciprofloxacin, Ceftriaxone and Trimethoprim/sulfamethoxazole
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 152 participants
- Where
- 3 sitesSingapore
- Study dates
- 5 Nov 2013to 16 Jan 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Inpatient at time of enrollment
- Age >= 21 years
- Computed tomography (CT) or ultrasound (US) within the preceding 7 days suggestive of a liver abscess, as defined by presence of one or more focal areas of hypo- or hyper-attenuation within the liver
- Klebsiella pneumoniae isolated from abscess fluid or blood collected within the preceding 7 days
- Able and willing to give informed consent
Who cannot join
- All subjects meeting any of the following exclusion criteria at baseline will be excluded from participation:
- 1) Polymicrobial abscess - additional organisms isolated from blood or abscess fluid within the preceding 7 days 2a) Klebsiella pneumoniae resistant to Ceftriaxone AND Ertapenem 2b) Klebsiella pneumoniae resistant to Ciprofloxacin AND Cotrimoxazole 3) On effective IV antibiotics > 7 days 4a) Hypersensitivity to cephalosporins AND carbapenems; as defined by history of rash, urticaria, angiodema, bronchospasm or circulatory collapse following prior administration.
- 4b) Hypersensitivity to fluoroquinolones AND sulpha drugs; as defined by history of rash, urticaria, angioedema, bronchospasm or circulatory collapse following prior administration.
- 4c) History of penicillin anaphylaxis (angioedema, bronchospasm or circulatory collapse). Subjects with a history of only rash or urticaria or unknown reaction to penicillin can be included.
- 5) Inability to take oral medications for any reason 6) Severe sepsis or septic shock defined as unresolved hypotension (MAP<70) or tachycardia (HR>110), or requirement of inotropic support or ventilation at time of eligibility. Should the subject's hypotension or tachycardia subsequently resolve, and they cease to require inotropes and ventilation within 7 days, they may be reconsidered for eligibility.
- 7) Established endophthalmitis at time of screening (patients with visual symptoms should have ophthalmology review prior to enrollment) 8) Established central nervous system abscess at time of screening (patients with focal neurology should have CT head prior to enrollment) 9) Women who are pregnant or breastfeeding 10) Inability to obtain consent from subject 11) Patients on tizanidine or theophylline 12) Patients on concomitant drugs that can result in prolongation of the QT interval (e.g., class IA or class III antiarrhythmics) or with risk factors for torsade de pointes (e.g., known QT prolongation, uncorrected hypokalemia) 13) Patients whose K. pneumoniae tests resistant to ciprofloxacin, and those with contraindications to ciprofloxacin will be tested for G6PD deficiency, and excluded if deficient 14) Severe immunocompromise (e.g., active leukemia or lymphoma, generalized malignancy, aplastic anemia, solid organ transplant, bone marrow transplant within 2 years of transplantation, or transplants of longer duration still on immunosuppressive drugs or with graft-versus-host disease, congenital immunodeficiency, current radiation therapy, HIV/AIDS with CD4 lymphocyte count <200 and patients or on immunosuppressant medications) 15) Creatinine clearance <15 ml/min
- defined as antibiotics to which the Klebsiella pneumoniae isolate in blood or abscess fluid is susceptible
Trial locations and contacts
3 sites in 1 country.
Singapore3 sites
Singapore General Hospital
Singapore, 169856
National University Hospital
Singapore
Tan Tock Seng Hospital
Singapore
About this study
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 Pneumoniae Liver Abscess
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.
- Conditions
- Liver Abscess, Pyogenic
- Being tested
- Ciprofloxacin, Ceftriaxone, Trimethoprim/sulfamethoxazole, Ertapenem
- Keywords
- Klebsiella pneumoniae
- Medical subject headings
- Liver Abscess, Pyogenic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CiprofloxacinDrug
CeftriaxoneDrug
Trimethoprim/sulfamethoxazoleDrug
Also called Bactrim
ErtapenemDrug
| Study group | Role | What they receive |
|---|---|---|
| Oral antibiotics | Experimental | 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). Receives: Drug: Ciprofloxacin; Drug: Trimethoprim/sulfamethoxazole |
| Intravenous antibiotics | Active comparator | 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). Receives: Drug: Ceftriaxone; Drug: Ertapenem |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 12
Secondary outcomes (1)
Clinical response
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.
Measured: Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2012 (estimated)
- Study start5 Nov 2013
- Primary completion16 Jan 2018
- Study completion16 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Liver Abscess, PyogenicStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 152 participants (actual)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- Tan Tock Seng Hospital, Singapore General Hospital
- Responsible party
- Sponsor
- Investigators
- Sophia Archuleta, MD, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01723150
- Sponsor's protocol ID
- A-KLASS
- Status last verified
- Aug 2018
- First submitted
- 22 Oct 2012
- Last updated
- 27 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 24176222Yoong 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.
PubMed 37328522Molton 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.
PubMed 31641767
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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 Pneumoniae Liver Abscess
- ClinicalTrials.gov ID
- NCT01723150
- Acronym / sponsor ID
- A-KLASS
- Conditions
- Liver Abscess, Pyogenic
- Keywords
- Klebsiella pneumoniae
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 152 participants (actual)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Collaborators
- Tan Tock Seng Hospital, Singapore General Hospital
- Study start
- 5 Nov 2013 (actual)
- Primary completion
- 16 Jan 2018 (actual)
- Study completion
- 16 Jan 2018 (actual)
- First posted
- 7 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral antibiotics | Experimental | Drug: Ciprofloxacin, Drug: Trimethoprim/sulfamethoxazoleThe 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). |
| Intravenous antibiotics | Active comparator | Drug: Ceftriaxone, Drug: ErtapenemThe active comparator arm continues intravenous antibiotics to complete 4 weeks of therapy. Intravenous antibiotics will be ceftriaxone (or ertapenem if the isolate is resistant). |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Inpatient at time of enrollment
- Age >= 21 years
- Computed tomography (CT) or ultrasound (US) within the preceding 7 days suggestive of a liver abscess, as defined by presence of one or more focal areas of hypo- or hyper-attenuation within the liver
- Klebsiella pneumoniae isolated from abscess fluid or blood collected within the preceding 7 days
- Able and willing to give informed consent
Key exclusion criteria (7 listed)
- All subjects meeting any of the following exclusion criteria at baseline will be excluded from participation:
- 1) Polymicrobial abscess - additional organisms isolated from blood or abscess fluid within the preceding 7 days 2a) Klebsiella pneumoniae resistant to Ceftriaxone AND Ertapenem 2b) Klebsiella pneumoniae resistant to Ciprofloxacin AND Cotrimoxazole 3) On effective IV antibiotics > 7 days 4a) Hypersensitivity to cephalosporins AND carbapenems; as defined by history of rash, urticaria, angiodema, bronchospasm or circulatory collapse following prior administration.
- 4b) Hypersensitivity to fluoroquinolones AND sulpha drugs; as defined by history of rash, urticaria, angioedema, bronchospasm or circulatory collapse following prior administration.
- 4c) History of penicillin anaphylaxis (angioedema, bronchospasm or circulatory collapse). Subjects with a history of only rash or urticaria or unknown reaction to penicillin can be included.
- 5) Inability to take oral medications for any reason 6) Severe sepsis or septic shock defined as unresolved hypotension (MAP<70) or tachycardia (HR>110), or requirement of inotropic support or ventilation at time of eligibility. Should the subject's hypotension or tachycardia subsequently resolve, and they cease to require inotropes and ventilation within 7 days, they may be reconsidered for eligibility.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ciprofloxacin | Drug | Oral antibiotics |
| Ceftriaxone | Drug | Intravenous antibiotics |
| Trimethoprim/sulfamethoxazoleAlso: Bactrim | Drug | Oral antibiotics |
| Ertapenem | Drug | Intravenous antibiotics |
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.
1 secondary outcome
Clinical response
Time frame: Week 4
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2018.
- Background: PubMed 24176222Molton 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.
- Derived from this study: PubMed 37328522Yoong 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.
- Derived from this study: PubMed 31641767Molton 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sophia Archuleta, MD principal investigator
National University Hospital, Singapore
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ciprofloxacin, Ceftriaxone and Trimethoprim/sulfamethoxazole in people with Liver Abscess, Pyogenic, run by National University Hospital, Singapore at 3 sites in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical cure (time frame: Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01723150, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2018.