Liver AbscessPhase 3CMETRONCT03969758
Ciprofloxacin Plus Metronidazole Vs Cefixime Plus Metronidazole Therapy for the Treatment of Liver Abscess
A Phase 3 study testing Ciprofloxacin and Cefixime in people with Liver Abscess, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
Trial summary
Liver abscess is purulent collections in the liver parenchyma that result from microbial infection spread to the liver through the biliary tree, hepatic or portal vein and by extension of adjacent infection or as a result of trauma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Abscess
- What is being tested?
- Ciprofloxacin and Cefixime
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 1 siteIndia
- Study dates
- Jul 2019to May 2020
- Phase
- Phase 3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Irrespective of gender
- Age ≥ 18 years
- Symptomatic patients of liver abscess confirmed with radiology imaging, either by ultrasonography (USG) or computed tomographgy (CT) scan
Who cannot join
- Past history of liver abscess
- Chronic kidney disease (CKD)
- History of hypersensitivity to either Ciprofloxacin or Metronidazole or Cefixime
- Shock (blood pressure <90/60 mmHg) at presentation
- ARDS (PaO2/FiO2≤300)
- Encephalopathy (altered sensorium with GCS <15)
Show all 11Show fewer
- Acute kidney injury (AKI, Increase in serum creatinine to ≥1.5 times from the baseline)
- Pregnancy at presentation
- Already received antibiotics for more than 48 hours prior to the admission
- Not able to take orally
- Receiving blood thinners like anti-platelets, anti-coagulation agents within 4 weeks of presentation
Trial locations and contacts
1 site in 1 country.
India1 site
Post Graduate Institute of Medical Education and Research
Chandigarh, 160012
About this study
Official title: Efficacy of Empirical Ciprofloxacin Plus Metronidazole and Cefixime Plus Metronidazole Therapy for the Treatment of Liver Abscess: A Randomised Controlled Clinical Trial
Liver abscess is purulent collections in the liver parenchyma that result from microbial infection spread to the liver through the biliary tree, hepatic or portal vein and by extension of adjacent infection or as a result of trauma. Liver abscesses are most commonly pyogenic followed by amoebic and rarely tuberculous or fungal in immunocompromised patients. In the developing country amoebic liver abscess is more frequent than the developed country but secondary bacterial infection of amoebic liver abscess and polymicrobial pyogenic liver abscess are also common.
Pyogenic liver abscess is commonly a polymicrobial infection caused by mixed enteric facultative and anaerobic pathogens. The most commonly isolated organisms are Escherichia coli, Klebsiella pneumoniae, Streptococcus constellatus, Streptococcus anginosus, Streptococcus intermedius, Enterococcus and anaerobes, including Bacteroidesfragilis and Fusobacteriumnecrophorum. Amoebic liver abscess most frequently occur following infection with the parasite Entamoeba histolytica.
Read more
Liver abscess is a common medical emergency. Prompt empirical antimicrobial with or without percutaneous aspiration or drainage of the abscess is therapeutic.
An empiric antimicrobial regimen for liver abscess should cover enteric gram-negative bacilli, streptococci, anaerobes and antamoebahistolytica. Presently a Fluoroquinolone (Ciprofloxacin, Levofloxacin) or a Third or Fourth generation Cefalosporine (Cefixime, Ceftriaxone, cefepime) or a Beta-lactam-beta-lactamase inhibitor combination (piperacillin-tazobactam or ticarcillin-clavulanate) or a Carbapenem (Imipenem-cilastatin, Meropenem, Doripenem, Ertapenem) are being used in combination with or without Metronidazole as the empirical antimicrobial regime for the treatment live abscess. There is no randomized controlled clinical trial to evaluated and compare efficacy of the antimicrobial regimens for the treatment of liver abscess as well as there is no specific treatment guideline for the use of empirical antibiotics. There is also no definite proven rational for using Cefalosporine, Beta-lactam-beta-lactamase inhibitor combination or Carbapenem upfront, not using Fluoroquinolone in empirical antibiotic regimen for the treatment of liver abscess. Injudicious use of broader spectrum antibiotics may also lead to rise in antibiotic resistance in future.
Both ciprofloxacin and Cefixime are effective oral antibiotics as they are well-absorbed orally with good oral bioavailability and achieve plasma concentration well above the minimal inhibitory concentrations require for the killing of the microorganism. Using intravenous (IV) antibiotics upfront, for the treatment of liver abscess in patients who can take orally may unnecessary increase the duration of hospital stay, healthcare burden and the cost of therapy, as well as the risk of hospital acquired infection.
So the investigators have planned this randomized controlled double blind study to evaluate the efficacy of empirical Ciprofloxacin plus Metronidazole and Cefixime plus Metronidazole therapy for the treatment of liver abscess and to compare the outcomes of two different empirical antibiotics regimen.
- Conditions
- Liver Abscess
- Being tested
- Ciprofloxacin, Cefixime
- Medical subject headings
- Liver Abscess
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CiprofloxacinDrug
Also called Metronidazole, Percutaneous drainage or aspiration of the liver abscess
will receive tablet Ciprofloxacin (500 mg BDS) and tablet Metronidazole (800 mg TDS) for 2 weeks orally. Percutaneous aspiration or drainage of the liver abscess will be done when there is enough liquid content/pus amenable for aspiration or drainage. Percutaneous drainage or aspiration will be done in liver abscess with size of ≥ 5 cm and <5 cm respectively.
CefiximeDrug
Also called Metronidazole, Percutaneous drainage or aspiration of the liver abscess
will receive tablet Cefixime (200 mg BDS) and tablet Metronidazole (800 mg TDS) for 2 weeks orally. Percutaneous aspiration or drainage of the liver abscess will be done when there is enough liquid content/pus amenable for aspiration or drainage. Percutaneous drainage or aspiration will be done in liver abscess with size of ≥ 5 cm and <5 cm respectively.
| Study group | Role | What they receive |
|---|---|---|
| Ciprofloxacin plus Metronidazole therapy | Active comparator | Will receive tablet Ciprofloxacin (500 mg BDS) and tablet Metronidazole (800 mg TDS) orally for 2 weeks. Percutaneous aspiration or drainage of the liver abscess will be done for all the participants when there is enough liquid content/pus which is amenable for aspiration or drainage. Percutaneous drainage or aspiration will be done in liver abscess with size of ≥ 5 cm and <5 cm respectively. After 2 weeks of empirical antibiotic therapy, asymptomatic patients with persistent drainage with USG showing significant drainable collection in the liver will receive another 2 weeks of extended antimicrobial therapy of same combination. Receives: Drug: Ciprofloxacin |
| Cefixime plus Metronidazole Therapy | Active comparator | Will receive tablet Cefixime (200 mg BDS) and tablet Metronidazole (800 mg TDS) orally for 2 weeks.Percutaneous aspiration or drainage of the liver abscess will be done for all the participants when there is enough liquid content/pus which is amenable for aspiration or drainage. Percutaneous drainage or aspiration will be done in liver abscess with size of ≥ 5 cm and <5 cm respectively. After 2 weeks of empirical antibiotic therapy, asymptomatic patients with persistent drainage with USG showing significant drainable collection in the liver will receive another 2 weeks of extended antimicrobial therapy of same combination. Receives: Drug: Cefixime |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical cure
Asymptomatic and afebrile for more than 48 hours, along with USG showing no drainable collection in the liver with removal of the pigtail catheter if any
Measured: 2 weeks
Secondary outcomes (9)
Treatment failure
Defined as any one of the following condition
- Persistently symptomatic with fever for more than 72 hours even after starting empirical antibiotics and percutaneous aspiration or drainage
- Development of new collection in the liver during the course of antibiotic therapy
- Development of shock and new onset organ failure ( Encephalopathy, ARDS, AKI) during the course of therapy, leading to shifting to IV antibiotics
- If culture of the aspirated or drained pus show growth of microorganism not sensitive to either Ciprofloxacin or Cefixime
Measured: 8 weeks
All-cause mortality
Total number of death
Measured: 8 weeks
Recurrence of liver abscess
Development new liver abscess after clinical cure during the 8 weeks follow up period
Measured: 8 weeks
Need for surgical intervention
number of patients needing surgical intervention for the treatment of liver abscess
Measured: 8 weeks
Need for mechanical ventilation
Number of patients needing mechanical ventilation for the respiratory failure.
Measured: 8 weeks
Need for prolong antibiotics 11.
Number of asymptomatic patients receiving 2 weeks of extended antibiotic therapy due to persistent drainage or aspiration even after 2 weeks of empirical antibiotics
Measured: 8 weeks
Duration of hospital stay
Number of days of hospital stay for the treatment of liver abscess
Measured: 8 weeks
Adverse drug events (ADE)
Number of adverse drug events
Measured: 8 weeks
Localised bio-availability of the drugs (Ciprofloxacin, Metronidazole and Cefixime)
Concentration of the drug in drained pus/Concentration of drug in the serum X100 on the day-three of the drainage (when applicable)
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2019
- Study startJul 2019 (estimated)
- Primary completionMay 2020 (estimated)
- Study completionMay 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver AbscessStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Deba Prasad Dhibar, Post Graduate Institute of Medical Education and Research, Chandigarh
- Investigators
- Deba P Dhibar, MD, Principal investigator, PGIMER, Chandigarh, India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03969758
- Sponsor's protocol ID
- INT/IEC/2019/001028
- Acronym
- CMETRO
- Status last verified
- Jul 2019
- First submitted
- 22 May 2019
- Last updated
- 22 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to share IPD with other researchers except for those are directly involved with this study.
Publications
Priya G L, Dhibar DP, Saroch A, Sharma N, Sharma V, Verma N, Chaluvashetty SB, Prakash A, Kaur H. Efficacy of empirical Ciprofloxacin or Cefixime plus Metronidazole therapy for the treatment of liver abscess: a randomized control clinical trial. Sci Rep. 2024 May 20;14(1):11430. doi: 10.1038/s41598-024-59607-1.
PubMed 38769330
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Empirical Ciprofloxacin Plus Metronidazole and Cefixime Plus Metronidazole Therapy for the Treatment of Liver Abscess: A Randomised Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT03969758
- Acronym / sponsor ID
- CMETRO / INT/IEC/2019/001028
- Conditions
- Liver Abscess
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- Jul 2019 (estimated)
- Primary completion
- May 2020 (estimated)
- Study completion
- May 2020 (estimated)
- First posted
- 31 May 2019 (actual)
- 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.
Liver abscess is purulent collections in the liver parenchyma that result from microbial infection spread to the liver through the biliary tree, hepatic or portal vein and by extension of adjacent infection or as a result of trauma. Liver abscesses are most commonly pyogenic followed by amoebic and rarely tuberculous or fungal in immunocompromised patients. In the developing country amoebic liver abscess is more frequent than the developed country but secondary bacterial infection of amoebic liver abscess and polymicrobial pyogenic liver abscess are also common.
Pyogenic liver abscess is commonly a polymicrobial infection caused by mixed enteric facultative and anaerobic pathogens. The most commonly isolated organisms are Escherichia coli, Klebsiella pneumoniae, Streptococcus constellatus, Streptococcus anginosus, Streptococcus intermedius, Enterococcus and anaerobes, including Bacteroidesfragilis and Fusobacteriumnecrophorum. Amoebic liver abscess most frequently occur following infection with the parasite Entamoeba histolytica.
Liver abscess is a common medical emergency. Prompt empirical antimicrobial with or without percutaneous aspiration or drainage of the abscess is therapeutic.
An empiric antimicrobial regimen for liver abscess should cover enteric gram-negative bacilli, streptococci, anaerobes and antamoebahistolytica. Presently a Fluoroquinolone (Ciprofloxacin, Levofloxacin) or a Third or Fourth generation Cefalosporine (Cefixime, Ceftriaxone, cefepime) or a Beta-lactam-beta-lactamase inhibitor combination (piperacillin-tazobactam or ticarcillin-clavulanate) or a Carbapenem (Imipenem-cilastatin, Meropenem, Doripenem, Ertapenem) are being used in combination with or without Metronidazole as the empirical antimicrobial regime for the treatment live abscess. There is no randomized controlled clinical trial to evaluated and compare efficacy of the antimicrobial regimens for the treatment of liver abscess as well as there is no specific treatment guideline for the use of empirical antibiotics. There is also no definite proven rational for using Cefalosporine, Beta-lactam-beta-lactamase inhibitor combination or Carbapenem upfront, not using Fluoroquinolone in empirical antibiotic regimen for the treatment of liver abscess. Injudicious use of broader spectrum antibiotics may also lead to rise in antibiotic resistance in future.
Both ciprofloxacin and Cefixime are effective oral antibiotics as they are well-absorbed orally with good oral bioavailability and achieve plasma concentration well above the minimal inhibitory concentrations require for the killing of the microorganism. Using intravenous (IV) antibiotics upfront, for the treatment of liver abscess in patients who can take orally may unnecessary increase the duration of hospital stay, healthcare burden and the cost of therapy, as well as the risk of hospital acquired infection.
So the investigators have planned this randomized controlled double blind study to evaluate the efficacy of empirical Ciprofloxacin plus Metronidazole and Cefixime plus Metronidazole therapy for the treatment of liver abscess and to compare the outcomes of two different empirical antibiotics regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ciprofloxacin plus Metronidazole therapy | Active comparator | Drug: CiprofloxacinWill receive tablet Ciprofloxacin (500 mg BDS) and tablet Metronidazole (800 mg TDS) orally for 2 weeks. Percutaneous aspiration or drainage of the liver abscess will be done for all the participants when there is enough liquid content/pus which is amenable for aspiration or drainage. Percutaneous drainage or aspiration will be done in liver abscess with size of ≥ 5 cm and <5 cm respectively. After 2 weeks of empirical antibiotic therapy, asymptomatic patients with persistent drainage with USG showing significant drainable collection in the liver will receive another 2 weeks of extended antimicrobial therapy of same combination. |
| Cefixime plus Metronidazole Therapy | Active comparator | Drug: CefiximeWill receive tablet Cefixime (200 mg BDS) and tablet Metronidazole (800 mg TDS) orally for 2 weeks.Percutaneous aspiration or drainage of the liver abscess will be done for all the participants when there is enough liquid content/pus which is amenable for aspiration or drainage. Percutaneous drainage or aspiration will be done in liver abscess with size of ≥ 5 cm and <5 cm respectively. After 2 weeks of empirical antibiotic therapy, asymptomatic patients with persistent drainage with USG showing significant drainable collection in the liver will receive another 2 weeks of extended antimicrobial therapy of same combination. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Irrespective of gender
- Age ≥ 18 years
- Symptomatic patients of liver abscess confirmed with radiology imaging, either by ultrasonography (USG) or computed tomographgy (CT) scan
Key exclusion criteria (11 listed)
- Past history of liver abscess
- Chronic kidney disease (CKD)
- History of hypersensitivity to either Ciprofloxacin or Metronidazole or Cefixime
- Shock (blood pressure <90/60 mmHg) at presentation
- ARDS (PaO2/FiO2≤300)
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 |
|---|---|---|
| CiprofloxacinAlso: Metronidazole, Percutaneous drainage or aspiration of the liver abscesswill receive tablet Ciprofloxacin (500 mg BDS) and tablet Metronidazole (800 mg TDS) for 2 weeks orally. Percutaneous aspiration or drainage of the liver abscess will be done when there is enough liquid content/pus amenable for aspiration or drainage. Percutaneous drainage or aspiration will be done in liver abscess with size of ≥ 5 cm and <5 cm respectively. | Drug | Ciprofloxacin plus Metronidazole therapy |
| CefiximeAlso: Metronidazole, Percutaneous drainage or aspiration of the liver abscesswill receive tablet Cefixime (200 mg BDS) and tablet Metronidazole (800 mg TDS) for 2 weeks orally. Percutaneous aspiration or drainage of the liver abscess will be done when there is enough liquid content/pus amenable for aspiration or drainage. Percutaneous drainage or aspiration will be done in liver abscess with size of ≥ 5 cm and <5 cm respectively. | Drug | Cefixime plus Metronidazole Therapy |
Primary outcome
Clinical cure
Time frame: 2 weeks
Asymptomatic and afebrile for more than 48 hours, along with USG showing no drainable collection in the liver with removal of the pigtail catheter if any
9 secondary outcomes
Treatment failure
Time frame: 8 weeks
All-cause mortality
Time frame: 8 weeks
Recurrence of liver abscess
Time frame: 8 weeks
Need for surgical intervention
Time frame: 8 weeks
Need for mechanical ventilation
Time frame: 8 weeks
Need for prolong antibiotics 11.
Time frame: 8 weeks
Duration of hospital stay
Time frame: 8 weeks
Adverse drug events (ADE)
Time frame: 8 weeks
Localised bio-availability of the drugs (Ciprofloxacin, Metronidazole and Cefixime)
Time frame: 8 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2019.
- Derived from this study: PubMed 38769330Priya G L, Dhibar DP, Saroch A, Sharma N, Sharma V, Verma N, Chaluvashetty SB, Prakash A, Kaur H. Efficacy of empirical Ciprofloxacin or Cefixime plus Metronidazole therapy for the treatment of liver abscess: a randomized control clinical trial. Sci Rep. 2024 May 20;14(1):11430. doi: 10.1038/s41598-024-59607-1.
- Individual participant dataSharing planned: No. There is no plan to share IPD with other researchers except for those are directly involved with this study.
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Liver Abscess
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.
Deba P Dhibar, MD principal investigator
PGIMER, Chandigarh, India
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ciprofloxacin and Cefixime in people with Liver Abscess, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
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 3 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 22 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Deba P Dhibar, MD (+91722756670, drdeba_prasad@yahoo.co.in), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical cure (time frame: 2 weeks). 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 NCT03969758, which also lists 1 linked publication.
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 22 Jul 2019.