FAMOUS Trial: Famotidine for the prevention of peptic ulcers and esophagitis in patients taking low-dose aspirin

A non-stop pharmaceutical battle…

FAMOUS trial is a Phase III, randomized, double blind, placebo-controlled trial funded by the pharmaceuticals Merck and Astellas and published in 2009. In this study, Taha et al, conclude that famotidine is effective in reducing gastric and duodenal ulcers as well as erosive esophagitis in patients who require daily aspirin intake. As a competitive inhibitor of histamine H2-receptors on the basolateral membrane of parietal cells, Famotidine reduces gastric acid secretion. It was first developed by the Japanese pharmaceutical Yamanouchi/Astellas and posteriorly marketed by Merck as Pepcid.

The study brought the attention of gastroenterologists and pharmaceuticals worldwide. Soon after, on 2010, Fook-Hong et al, demonstrated that Famotidine is inferior to Pantoprazole in preventing recurrence of aspirin-related peptic ulcers or erosions. This clinical trial followed patients for 48 weeks (in contrast to 12-week follow-up in FAMOUS trial) and the authors reported no conflicts of interest. Years before FAMOUS trial was conducted, Taha et al, demonstrated on 1996 that high dose Famotidine reduces the risk of NSAID induced gastric and duodenal ulcers particularly important for patients with arthritis who require long-term NSAID use. A multicenter study that used a protocol similar to the trial by Taha et al, failed to demonstrate the benefits of Famotidine in preventing NSAID-induced gastric ulcers, however, this controversial study was never published as a full paper.

Where at we at, 22 years later?

On 2012, REDUCE trials 1&2 by Laine et al, tested a single-tablet combination of Ibuprofen and Famotidine in prevention of gastric ulcers with a very small, yet statistically significant, benefit for the treatment group. Furthermore, on 2014, Whellan et al , demonstrated that a combined enteric coated aspirin/omeprazole tablet reduces endoscopic gastric ulcers while improving ASA compliance in cardiac patients due to less GI side effects.

On 2018, we count with 2 combination drugs: Duexis (Ibuprofen/Famotidine) approved on 2011, 90 tabs cost $2883.67, and Vimovo (Naproxen/Esomeprazole) approved on 2010, 60 day cost $2473.37.

In conclusion, the work by Taha has opened a Pandora’s box for extensive research that is left to be done, moreover, it has prepared the field for a never ending pharmaceutical battle.

Daniela Guerrero Vinsard MD.
University of Connecticut Health Center.
Department of Internal Medicine.

Source: The Lancet