Amoebic Liver Abscess, Liver Abscess
Conditions
Keywords
Liver abscess, Amoebic liver abscess, Diloxanide furoate
Brief summary
Liver abscess is a common cause of presentation to medical emergency. Among the various causes of liver abscess, Amoebic liver abscess (ALA) is a frequent cause that can resemble pyogenic infections in tropical regions. Prompt diagnosis and empirical antimicrobials along with drainage or aspiration produces successful clinical recovery. Metronidazole has been the cornerstone of ALA therapy and achieves clinical cure in approximately 90% of uncomplicated cases. It is active against both luminal and tissue forms of Entamoeba histolytica, however it has relatively limited effect against the intestinal (luminal) form of parasite, so intestine may remain colonized after apparent resolution. This persistent intestinal carriage can lead to relapse or ongoing transmission. This prompts physicians to consider Diloxanide furoate as additional luminal agent for treatment of ALA along with metronidazole therapy. Diloxanide furoate is traditionally administered after metronidazole to eradicate residual intestinal infection and lower relapse rates. However, many patients receive only metronidazole because of cost, limited awareness about luminal therapy, poor adherence, or absence of local comparative evidence. Studies have shown that 30-40% of patients can have inadequate luminal parasite clearance following standard metronidazole therapy for ALA. Frequent relapses have been seen in ALA after treatment with metronidazole. As per literature, Diloxanide furoate eradicates intraluminal cysts in approximately 85-95% of patients with non-invasive amoebiasis. It remains unclear whether giving Diloxanide furoate at the same time as Metronidazole has any additional benefit compared with Metronidazole alone for patients with ALA. Theoretically, addition of diloxanide furoate could increase overall cure rate, rapid parasite clearance and reduce recurrence. However, there is no randomized controlled trial available at present to address the research question whether dual therapy with Diloxanide furoate with Metronidazole has any added benefits in ALA. So, this randomized controlled trial has been planned to evaluate whether adding Diloxanide furoate to Metronidazole treatment improves outcomes. This study will generate robust data to formulate/modify the existing guidelines of management of ALA especially in endemic areas. Research question: Whether addition of Diloxanide furoate with Metronidazole is more efficacious than Metronidazole monotherapy for treatment of amoebic liver abscess in terms of achieving better clinical cure, parasitic clearance and reduced recurrence.
Detailed description
STUDY DESIGN: Prospective, randomised controlled, double blinded, clinical trial Population(P): Patients with newly diagnosed amoebic liver abscess presenting to Post graduate Institute of Medical Education and Research, Chandigarh Intervention(I): Diloxanide furoate plus Metronidazole therapy Comparison(C): Metronidazole monotherapy plus placebo Outcome(O): Clinical cure rate, parasite clearance and recurrence rate at 8 weeks follow up Time(T): September 2026 to July 2027
Interventions
DRUGDiloxanide furoate
Diloxanide furoate group will receive oral Diloxanide furoate 500mg 1 tab TDS for 10 days
OTHERPlacebo
matched placebo 1 tab TDS for 10 days
Sponsors
Post Graduate Institute of Medical Education and Research, Chandigarh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
randomized controlled clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>18 years * Male or Female * Patients with newly diagnosed amoebic liver abscess
Exclusion criteria
* Patients not able to take orally * Patients receiving antimicrobials for more than 72 hours before the enrolment in the study * History of hypersensitivity reactions to Metronidazole or Diloxanide furoate * Pregnancy * Patients on antiplatelets/anticoagulation within 4 weeks of presentation * Presentation with shock (SBP\<90 and/ or DBP\< 60 mmHg) * Patients with ARDS (SpO2 ≤92%, PaO2/Fio2\<300, requiring oxygen therapy) * Patients with renal dysfunction / CKD (Creatinine \>1.5mg/dl) * Patients with altered sensorium (GCS \<15) * Patients with known malignancy * Patients with HIV * Not willing for informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical cure | 8 weeks | "Clinical cure" is defined as number of participants becoming asymptomatic with fever resolution for ≥48 hours, including USG demonstrating no drainable collection in the liver along with removal of the pigtail catheter if any. |
| Treatment failure | 8 weeks | "Treatment failure" is defined as the number of participants fulfilling of any one or more of the following conditions: 1. Persistently symptomatic even after 72 h of antimicrobial therapy and percutaneous aspiration or drainage of the hepatic collection 2. Emergence of new collection in the liver during the course of antimicrobial therapy 3. Emergence of shock and or new onset organ failure (Encephalopathy, ARDS, AKI, MODS) during the course of therapy e. Patients requiring persistent drainage or repeated aspiration of the abscess even after 4 weeks of antimicrobial therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1. Parasitic clearance | 8 weeks | Number of participant's Stool EH DNA PCR becomes negative after initial positive test at 2 \& 8 weeks. |
| Recurrence of liver abscess | 8 weeks | Number of participants with occurrence of new liver abscess after achieving clinical cure during 8 weeks of follow up. |
| Duration of the therapy | 8 weeks | Number of days of antimicrobial therapy required to achieve clinical cure |
| Adverse drug reaction (ADR) | 8 weeks | Incidence of adverse drug reaction related to the ongoing antimicrobial therapy. |
Countries
India
Contacts
CONTACTDeba Prasad Dhibar, MD
CONTACTHARLEEN SOOD, MD
Outcome results
None listed