Paromomycin or Metronidazole for Symptomatic Dientamoeba Fragilis in Adults (COMFORTER Trial) - Protocol for a Superiority Double Blind, Randomized Controlled Trial

Introduction Dientameba Fragilis (D.fragilis) is a protozoan found in the digestive tract - in the human colon. The route of transmission is fecal-oral, and infection can lead to chronic gastrointestinal symptoms manifested by abdominal pain, diarrhea, abdominal bloating, anal pruritus, and in addition pronounced fatigue [1]. Since the introduction of a molecular diagnosis [PCR] for a stool test, it has become clear that these protozoa are a main protozoa inhabiting the digestive system, with stool positivity rates ranging from 12 to 68%, depending on country and age [2].

This parasite was first identified about 100 years ago and since then debates have continued in the medical literature as to whether it is indeed a pathogen or a commensal [3]. In addition, there are disagreements regarding the preferred treatment for these cases, with several regimens tested in mostly small observational studies. Several drugs are currently recommended for D.fragilis, with metronidazole most commonly used [4]. However, metronidazole therapy for treating dientamoebiasis in children was not associated with better clinical outcomes in a randomized, double-blinded and placebo-controlled clinical trial. Furthermore despite observing higher eradication rates two weeks after end of therapy with metronidazole in this trial, positivity rebounded quickly appeared after therapy. [5]. In contrast, several observational studies have reported high clinical and microbiological success rates with paromomycin, with over 80% eradication in adults [6,7]. We could not identify any prospective study comparing head to head these two drugs; metronidazole and paromomycin.

In light of the above, we plan to perform a double blind, randomized controlled trial, evaluating the clinical and microbiological efficacy of paromomycin versus metronidazole for the treatment of symptomatic adults with PCR positive dientamoeba fragilis.

The primary outcomes is clinical improvement or resolution (yes/no. Secondary outcomes include clinical improvement evaluated by a visual analogue scale; microbiological eradication, quality of life, and adverse events related to therapy.

Aim