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Ciprofloxacin Plus Metronidazole Vs Cefixime Plus Metronidazole Therapy for the Treatment of Liver Abscess (CMETRO)

Primary Purpose

Liver Abscess

Status
Unknown status
Phase
Phase 3
Locations
India
Study Type
Interventional
Intervention
Ciprofloxacin
Cefixime
Sponsored by
Postgraduate Institute of Medical Education and Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Abscess

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Irrespective of gender
  • Age ≥ 18 years
  • Symptomatic patients of liver abscess confirmed with radiology imaging, either by ultrasonography (USG) or computed tomographgy (CT) scan

Exclusion Criteria:

  • 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)
  • 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

Sites / Locations

  • Post Graduate Institute of Medical Education and Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Ciprofloxacin plus Metronidazole therapy

Cefixime plus Metronidazole Therapy

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
All-cause mortality
Total number of death
Recurrence of liver abscess
Development new liver abscess after clinical cure during the 8 weeks follow up period
Need for surgical intervention
number of patients needing surgical intervention for the treatment of liver abscess
Need for mechanical ventilation
Number of patients needing mechanical ventilation for the respiratory failure.
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
Duration of hospital stay
Number of days of hospital stay for the treatment of liver abscess
Adverse drug events (ADE)
Number of adverse drug events
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)

Full Information

First Posted
May 22, 2019
Last Updated
July 19, 2019
Sponsor
Postgraduate Institute of Medical Education and Research
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1. Study Identification

Unique Protocol Identification Number
NCT03969758
Brief Title
Ciprofloxacin Plus Metronidazole Vs Cefixime Plus Metronidazole Therapy for the Treatment of Liver Abscess
Acronym
CMETRO
Official Title
Efficacy of Empirical Ciprofloxacin Plus Metronidazole and Cefixime Plus Metronidazole Therapy for the Treatment of Liver Abscess: A Randomised Controlled Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Unknown status
Study Start Date
July 2019 (Anticipated)
Primary Completion Date
May 2020 (Anticipated)
Study Completion Date
May 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Postgraduate Institute of Medical Education and Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Abscess

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
Double Blind
Allocation
Randomized
Enrollment
140 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ciprofloxacin plus Metronidazole therapy
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Cefixime plus Metronidazole Therapy
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ciprofloxacin
Other Intervention Name(s)
Metronidazole, Percutaneous drainage or aspiration of the liver abscess
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cefixime
Other Intervention Name(s)
Metronidazole, Percutaneous drainage or aspiration of the liver abscess
Intervention Description
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.
Primary Outcome Measure Information:
Title
Clinical cure
Description
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
Time Frame
2 weeks
Secondary Outcome Measure Information:
Title
Treatment failure
Description
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
Time Frame
8 weeks
Title
All-cause mortality
Description
Total number of death
Time Frame
8 weeks
Title
Recurrence of liver abscess
Description
Development new liver abscess after clinical cure during the 8 weeks follow up period
Time Frame
8 weeks
Title
Need for surgical intervention
Description
number of patients needing surgical intervention for the treatment of liver abscess
Time Frame
8 weeks
Title
Need for mechanical ventilation
Description
Number of patients needing mechanical ventilation for the respiratory failure.
Time Frame
8 weeks
Title
Need for prolong antibiotics 11.
Description
Number of asymptomatic patients receiving 2 weeks of extended antibiotic therapy due to persistent drainage or aspiration even after 2 weeks of empirical antibiotics
Time Frame
8 weeks
Title
Duration of hospital stay
Description
Number of days of hospital stay for the treatment of liver abscess
Time Frame
8 weeks
Title
Adverse drug events (ADE)
Description
Number of adverse drug events
Time Frame
8 weeks
Title
Localised bio-availability of the drugs (Ciprofloxacin, Metronidazole and Cefixime)
Description
Concentration of the drug in drained pus/Concentration of drug in the serum X100 on the day-three of the drainage (when applicable)
Time Frame
8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Irrespective of gender Age ≥ 18 years Symptomatic patients of liver abscess confirmed with radiology imaging, either by ultrasonography (USG) or computed tomographgy (CT) scan Exclusion Criteria: 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) 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Deba P Dhibar, MD
Phone
+91722756670
Email
drdeba_prasad@yahoo.co.in
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Deba P Dhibar, MD
Organizational Affiliation
PGIMER, Chandigarh, India
Official's Role
Principal Investigator
Facility Information:
Facility Name
Post Graduate Institute of Medical Education and Research
City
Chandigarh
ZIP/Postal Code
160012
Country
India

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
There is no plan to share IPD with other researchers except for those are directly involved with this study.

Learn more about this trial

Ciprofloxacin Plus Metronidazole Vs Cefixime Plus Metronidazole Therapy for the Treatment of Liver Abscess

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