Table 1.

Clinical trials with or without lactoferrin or standard therapy with or without lactoferrin.

Subjects	Study Design	Study Groups	Results	References
59 volunteers	Randomized controlled trial	(1) b-LF-treated group; (2) placebo-treated control group	Suppression of H. pylori colonization	Okuda et al., 2005 [31]
150 patients	Open randomized single-center study (preliminary results)	(1) Triple therapy (rabeprazole, clarithromycin, tinidazole) + LF for 7 days; (2) triple therapy (rabeprazole, clarithromycin, tinidazole) for 7 days; (3) triple therapy (rabeprazole, clarithromycin, tinidazole) for 10 days	Significantly higher eradication rate in triple therapy + LF than other groups	Di Mario et al., 2003 [72]
150 patients	Open randomized single-center study	(1) Triple therapy (rabeprazole, clarithromycin, tinidazole) + LF for 7 days; (2) triple therapy (rabeprazole, clarithromycin, tinidazole) for 7 days; (3) triple therapy (rabeprazole, clarithromycin, tinidazole) for 10 days	Significantly higher eradication rate in triple therapy + LF than other groups	Di Mario et al., 2003 [73]
402 patients	Open, randomized, multicenter, prospective study	(1) Triple therapy (esomeprazole, clarithromycin, tinidazole) for 7 days; (2) b-LF for 7 days followed by triple therapy (esomeprazole, clarithromycin, tinidazole) for 7 days; (3) triple therapy (rabeprazole, clarithromycin, tinidazole) + b-LF for 7 days	The eradication rate was significantly higher in patients receiving b-LF	Di Mario et al., 2006 [74]
70 patients	Prospective randomized clinical trial after failure of first standard treatment	(1) Ranitidine bismuth citrate, esomeprazole, amoxycillin, tinidazole; (2) ranitidine bismuth citrate, esomeprazole, amoxycillin, tinidazole + b-LF	The group receiving b-LF showed a higher but not statistically significant eradication rate.	Tursi et al., 2007 [75]
206 patients	Prospective randomized study	(1) Triple therapy (esomeprazole, clarithromycin, tinidazole); (2) triple therapy (esomeprazole, clarithromycin, tinidazole) + b-LF + probiotics	The eradication rate was 92.1% in the group receiving triple therapy + b-LF + probiotics and 76% in the group receiving only the standard triple therapy	De Bortoli et al., 2007 [76]
133 patients	Prospective, open l-label, three-center, randomized study	(1) Triple therapy (esomeprazole, clarithromycin, amoxycillin); (2) triple therapy (esomeprazole, clarithromycin, tinidazole) + bLF for 7 days	The eradication rate was 80.3% in the group receiving triple therapy + b-LF and 77.9% in the group receiving only the standard triple therapy. No significant difference between groups	Zullo et al., 2005 [77]
144 patients	Prospective, open l-label, multicenter, randomized study	(1) Triple therapy (rabeprazole, levofloxacin, amoxycillin) for 7 days; (2) triple therapy (esomeprazole, clarithromycin, tinidazole) + b-LF for 7 days	The eradication rate was 69.1% (per protocol analysis) in the group receiving triple therapy and 76.5% in the group receiving quadruple therapy	Zullo et al., 2007 [78]
9 randomized clinical trials (n = 1343 subjects)	Meta-analysis	(1) Triple therapy (proton-pump inhibitor + 2 antibiotics) or quadruple therapy (proton-pump inhibitor + bismuth + 2 antibiotics; or ranitidine bismuth citrate + same antibiotics); (2) b-LF-including regimens	The eradication rate was 86.57% in the group receiving standard therapy + b-LF and 74.44% in the group receiving only standard therapy	Zou et al., 2009 [79]
5 randomized clinical trials (n = 682 subjects)	Meta-analysis	(1) Standard therapy; (2) standard therapy + b-LF	The pooled odds ratio by intention-to-treat analysis in the b-LF vs. non-b-LF group was 2.22 and 2.24 using the fixed effects model and the random effects model, respectively	Sachdeva et al., 2009 [80]
400 patients	Randomized controlled clinical trial	(1) Proton pump inhibitor-based triple therapy for 2 weeks; (2) sequential therapy for 2 weeks; (3) proton-pump-based triple therapy + b-LF for 2 weeks; (4) sequential therapy + b-LF for 2 weeks	The success rates were 70.3%, 82.8%, 85.6%, and 94.5% in groups (1), (2), (3), and (4), respectively	Hablass et al., 2020 [81]