LAUSR

Abstract Background Prevention of colorectal adenomas (CA) is likely to prevent colorectal cancer (CRC). Nutri- or chemoprevention of CRC is not yet established. NSAIDs show some benefit but also increase the bleeding risk. Agents with a more favourable benefit/risk ratio are desirable. Preclinical and small clinical trials suggest that epigallocatechingallate (EGCG), a major polyphenol in green tea, has a good safety profile and antineoplastic effects in the large bowel, but there are no data from large trials. MIRACLE enrolled 1001 patients to examine the effect of a three year intake of ECGC on the recurrence of CA after polypectomy. Methods Double-blinded, placebo-controlled trial, 41 recruiting German centers, recruitment 12/2011-6/2015. Patients aged 50-80 years who underwent polypectomy within the last 6 months and tolerated EGCG well during a one month run-in were randomized to standardized decaffeinated EGCG (150 mg bid) or placebo for 3 years. Primary endpoint: Incidence of metachronous CA at the 3 year follow-up colonoscopy. Secondary endpoints: Occurrence, number, localization, size, histological subtype of CA, frequency of CRC and biomarker. Strata: Study center and intake of low-dose aspirin (≤100 mg/d). Results Clinical parameters were well balanced between the groups. Primary endpoint was analysed in the modified ITT set (modITT; n = 309 patients in EGCG, n = 323 in placebo group giving informed consent and undergoing 3 year follow up colonoscopy in the requested time frame). n = 102 patients in the EGCG and n = 103 in the placebo group were excluded due to missing follow up colonoscopy. Incidence of one or more CA after 3 year of placebo or EGCG 150 mg bid was 55.7 % and 51.1%, respectively (one sided adj. P = 0.077, adj. RR 0.904) in the modITT. In the per protocol set constituting all modITT patients completing the study without major protocol violations the respective figures were 54.3 % in the placebo and 48.3% in the EGCG group (one sided adj. P = 0.058, adj. RR 0.883). There were no safety issues and no major differences in AEs between EGCG and placebo during the randomized phase. Conclusions 300 mg EGCG per day was well tolerated and showed a trend towards a preventive effect on CA in the large bowel though not statistically significant. Clinical trial identification NCT01360320. Legal entity responsible for the study Martin-Luther-Universitat Halle-Wittenberg, Germany. Funding German Cancer Aid (Stiftung Deutsche Krebshilfe). Disclosure All authors have declared no conflicts of interest.