Aims:
Topically applied methylene blue dye chromoendoscopy is effective in improving detection of colorectal neoplasia. When combined with a pH- and time-dependent multimatrix structure, a per-oral formulation methylene blue formulation (MB-MMX) is directly delivered to colorectal mucosa.
Methods:
In a Phase III study, 50-to75-year-old patients scheduled for colorectal cancer screening or surveillance colonoscopy were randomized between 200 mg MB-MMX, placebo, or 100 mg MB-MMX in a ratio of 2:2:1. The 100 mg MB-MMX arm was only for masking purposes. MB-MMX and placebo tablets were administered with a 4 liters polyethylene glycol-based bowel preparation. The primary endpoint was the proportion of patients with one adenoma or carcinoma (adenoma detection rate [ADR]) expressed as odds ratio (OR) with 95% CI between the 200 mg MB-MMX and placebo groups, while false-positive (resection rate for non-neoplastic polyps) and adverse event rates were secondary endpoints.
Results:
Across 1,205 randomized patients, ADR was higher with MB-MMX (273/485[56.29%]) than the placebo (229/479[47.81%]; OR: 1.46[1.09, 1.96]). The proportion of patients with nonpolypoid lesion was higher with MB-MMX than the placebo (213/485[43.92%] vs. 168/479 [35.07%]; OR: 1.66[1.21, 2.26]), as was that for ≤5 mm adenomas (180/485[37.11%] vs. 148/479 [30.90%]; OR: 1.36[1.01, 1.83]), while no difference for those with polypoid or larger lesions was observed. The false-positive rate was similar across the study arms (MB-MMX:83/356[23.31%] vs. placebo: 97/326[29.75%]). Overall, 0.7% of patients had severe adverse events with no difference between the two arms.
Conclusions:
MB-MMX led to an absolute 8.5% ADR improvement without increasing the removal of non-neoplastic lesions.
