Efficacy of Diloxanide Furoate as Additional Luminal Agent Along With Metronidazole for the Treatment of Amoebic Liver Abscess (DFALA RCT)

Efficacy of Diloxanide Furoate as Additional Luminal Agent Along With Metronidazole for the Treatment of Amoebic Liver Abscess: A Randomized Controlled Clinical Trial

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 (1). 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 (2). 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 (3). Frequent relapses have been seen in ALA after treatment with metronidazole (4,5). As per literature, Diloxanide furoate eradicates intraluminal cysts in approximately 85-95% of patients with non-invasive amoebiasis (6).

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Abscess; Amoebic Liver Abscess
• Intervention / Treatment: Drug: Diloxanide furoate; Other: Placebo

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

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Deba Prasad Dhibar, MD; Phone Number: +911722756670; Email: drdeba_prasad@yahoo.co.in
• Study Contact Backup: Name: HARLEEN SOOD, MD; Phone Number: +911722756670; Email: harleen.sood@gmail.com

Study Locations

• India
  • Chandigarh
    • Chandigarh, Chandigarh, India, 160012
      • Post Graduate Institute of Medical Education and Research, Chandigarh, India
      • Contact: Deba Prasad Dhibar, MD; Phone Number: +911722756670; Email: drdeba_prasad@yahoo.co.in

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age >18 years 2. Male or Female 3. Patients with newly diagnosed amoebic liver abscess

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Exclusion Criteria:

1. Patients not able to take orally
2. Patients receiving antimicrobials for more than 72 hours before the enrolment in the study
3. History of hypersensitivity reactions to Metronidazole or Diloxanide furoate
4. Pregnancy
5. Patients on antiplatelets/anticoagulation within 4 weeks of presentation
6. Presentation with shock (SBP<90 and/ or DBP< 60 mmHg)
7. Patients with ARDS (SpO2 ≤92%, PaO2/Fio2<300, requiring oxygen therapy)
8. Patients with renal dysfunction / CKD (Creatinine >1.5mg/dl)
9. Patients with altered sensorium (GCS <15)
10. Patients with known malignancy
11. Patients with HIV
12. Not willing for informed consent -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diloxanide furoate group; Diloxanide furoate group will receive oral Diloxanide furoate 500mg 1 tab TDS for 10 days plus standard care of Metronidazole i.e. intravenous 750mg TDS or oral 800mg 1 tab TDS for 14 days.	Drug: Diloxanide furoate; Diloxanide furoate group will receive oral Diloxanide furoate 500mg 1 tab TDS for 10 days; Other Names: Standard care of Metronidazole i.e. intravenous 750mg TDS or oral 800mg 1 tab TDS for 14 days.
Placebo Comparator: Placebo group; Will receive matched placebo 1 tab TDS for 10 days plus stand care of Metronidazole i.e. intravenous 750mg TDS or oral 800mg 1 tab TDS for 14 days.	Other: Placebo; matched placebo 1 tab TDS for 10 days; Other Names: Standard care of Metronidazole i.e. intravenous 750mg TDS or oral 800mg 1 tab TDS for 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical cure	"Clinical cure" is defined as 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.	8 weeks
Treatment failure	"Treatment failure" is defined as the fulfilling of any one or more of the following conditions: Persistently symptomatic even after 72 h of antimicrobial therapy and percutaneous aspiration or drainage of the hepatic collection; Emergence of new collection in the liver during the course of antimicrobial therapy; 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	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1. Parasitic clearance	Stool EH DNA PCR becomes negative after initial positive test at 2 & 8 weeks.	8 weeks
Recurrence of liver abscess	Occurrence of new liver abscess after achieving clinical cure during 8 weeks of follow up.	8 weeks
Duration of the therapy	Number of days of antimicrobial therapy required to achieve clinical cure	8 weeks
Adverse drug reaction (ADR)	Incidence of adverse drug reaction related to the ongoing antimicrobial therapy.	8 weeks

Collaborators and Investigators

• Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh

Study record dates

Study Major Dates

• Study Start (Estimated): September 4, 2026
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: September 2, 2026
• First Submitted That Met QC Criteria: September 2, 2026
• First Posted (Actual): September 8, 2026

Study Record Updates

• Last Update Posted (Actual): September 8, 2026
• Last Update Submitted That Met QC Criteria: September 2, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Liver abscess; Amoebic liver abscess; Diloxanide furoate
• Additional Relevant MeSH Terms: Infections; Digestive System Diseases; Liver Diseases; Protozoan Infections; Parasitic Diseases; Suppuration; Amebiasis; Abscess; Liver Diseases, Parasitic; Abdominal Abscess; Liver Abscess; Liver Abscess, Amebic; diloxanide furoate; tyramine-deoxysorbitol
• Other Study ID Numbers: IEC-INT/2026/DM-4109

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All data requests should be submitted to the principal investigator (DPD) for consideration.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No