Effect of chemoprevention by low-dose aspirin of new or recurrent colorectal adenomas in patients with Lynch syndrome (AAS-Lynch): study protocol for a multicenter, double-blind, placebo-controlled randomized controlled trial
Authors: Soualy Adil , Deutsch David , Benallaoua Mourad , Ait-Omar Amal , Mary Florence , Helfen Sabine , Boubaya Marouane , Levy Vincent , Benamouzig Robert ,   the AAS-Lynch group, Benamouzig Robert , Mary Florence , Aït Omar Amal , Benallaoua Mourad , Helfen Sabine , Al-Khafaji Semaher , Demare Noémie , Perkins Géraldine , Laurent-Puig Pierre , Saurin Jean-Christophe , Raby Naouele , Venat-Bouvet Laurence , Penaud Corinne , Bonnet Delphine , Sicart Virginie , Pomes Chloé , Lecomte Thierry , Jollivet Claire , Caulet Morgane , Chaussade Stanislas , Dhooge Marion , Maksimovic Fanny , Grandval Philippe , Olschwang Sylvie , Saussereau Maud , Bellanger Jérôme , Netter-Coti Anne , Delhomelle Hélène , Buecher Bruno , Mehdi Lydia , Lejeune Sophie , Brahimi Afane , Cattan Stéphane , Bellengier Laurence , Tougeron David , Rafert Sandrine , Barouk Simonet Emmanuelle , Cornelis François , Serova-Erard Anna , Malka David , Gesta Paul , Oddoz Jeanne , Mari Véronique , Lesourd Samuel , Kergoat Gaëlle , Crivelli Louise , Sobhani Iradj , Amiot Aurélien , Lepage Côme , Faivre-Olivier Laurence , Jouve Jean-Louis , Drouillard Antoine , Perot Nora , Bardou Marc , Nambot Sophie , Mekahli Nadia , Lortholary Alain , Lenne Carole , Lagasse Jean-Paul , Ouahrani Brahim , Frebourg Thierry , Parodi Nathalie , Branchaud Maud , Desseigne Françoise , Grinand Elodie , Ingster Olivier , Semelin Benoit , Fein Francine , Lourenco Nelson , Aparicio Thomas , Brasseur Mathilde , Lopez Anthony 
Published: September 2020

Abstract
Lynch syndrome (LS) is the most common cause of inherited colorectal cancer (CRC) and confers a high lifetime risk of CRC estimated to be up to 60%. Colonoscopy is recommended every 2 years in LS patients above the 20–25-year-old age bracket, and every year when colonic neoplasia has been detected. Efficient chemoprevention has the potential to represent a cost-effective intervention in these high-risk patients and could allow a delay in colonoscopy surveillance. Several epidemiological studies have shown that regular use of low dose aspirin is associated with a 20 to 30% reduction in the risk of sporadic colonic adenomas and colorectal cancer regardless of family risk. However, in recent large randomized trials in specific populations, aspirin use showed no protection for colorectal cancer. A prospective randomized CAPP-2 trial evaluated the effect of aspirin use in LS patients. The primary analysis of this trial showed no significant decrease in CRC in LS patients under daily aspirin. However, a preplanned secondary analysis after an extended follow-up showed a significant reduced risk of CRC in the aspirin group in the per-protocol analysis. The real effect and clinical benefit of aspirin are still to be consolidated in this population. The AAS-Lynch trial—a prospective, multicentric, double-blind, placebo-controlled, randomized clinical trial—was designed to investigate if daily aspirin therapy, at a dose of 100 or 300 mg, would decrease the occurrence or recurrence of colorectal adenomas in patients under 75 years of age, compared with placebo.

Trial registration
ClinicalTrials.gov NCT02813824. Registered on 27 June 2016. The trial was prospectively registered.