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

Liver Abscess Clinical Trial

— 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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03969758
• Other study ID #: INT/IEC/2019/001028
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: July 2019
• Est. completion date: May 2020

Study information

• Verified date: July 2019
• Source: Postgraduate Institute of Medical Education and Research
• Contact: Deba P Dhibar, MD
• Phone: +91722756670
• Email: drdeba_prasad[@]yahoo.co.in
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 140
• Est. completion date: May 2020
• Est. primary completion date: May 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Abscess
• Liver Abscess

Intervention

Drug:
• Ciprofloxacin
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.
• Cefixime
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.

Locations

Country	Name	City	State
India	Post Graduate Institute of Medical Education and Research	Chandigarh

Sponsors (1)

Lead Sponsor	Collaborator
Postgraduate Institute of Medical Education and Research

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	2 weeks
Secondary	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	8 weeks
Secondary	All-cause mortality	Total number of death	8 weeks
Secondary	Recurrence of liver abscess	Development new liver abscess after clinical cure during the 8 weeks follow up period	8 weeks
Secondary	Need for surgical intervention	number of patients needing surgical intervention for the treatment of liver abscess	8 weeks
Secondary	Need for mechanical ventilation	Number of patients needing mechanical ventilation for the respiratory failure.	8 weeks
Secondary	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	8 weeks
Secondary	Duration of hospital stay	Number of days of hospital stay for the treatment of liver abscess	8 weeks
Secondary	Adverse drug events (ADE)	Number of adverse drug events	8 weeks
Secondary	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)	8 weeks