Clinical trial NCT03969758: Ciprofloxacin Plus Metronidazole Vs Cefixime Plus Metronidazole Therapy for the Treatment of Liver Abscess
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
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Liver Abscess
Lead sponsor: PGIMER
Sponsor class: UNKNOWN
First posted: 2019-05-31
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Clinical cure
timeFrame: 2 weeks
Secondary outcomes:
measure: Treatment failure
timeFrame: 8 weeks
measure: All-cause mortality
timeFrame: 8 weeks
measure: Recurrence of liver abscess
timeFrame: 8 weeks
measure: Need for surgical intervention
timeFrame: 8 weeks
measure: Need for mechanical ventilation
timeFrame: 8 weeks
measure: Need for prolong antibiotics 11.
timeFrame: 8 weeks
measure: Duration of hospital stay
timeFrame: 8 weeks
measure: Adverse drug events (ADE)
timeFrame: 8 weeks
measure: Localised bio-availability of the drugs (Ciprofloxacin, Metronidazole and Cefixime)
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: Post Graduate Institute of Medical Education and Research
Study officials:
affiliation: PGIMER, Chandigarh, India
name: Deba P Dhibar, MD
role: PRINCIPAL_INVESTIGATOR
References: