Christophe Bureau1, Dominique Thabut2, Caroline Jezequel3, Isabelle Archambeaud4, Louis D'Alteroche5, Sêbastien Dharancy6, Patrick Borentain7, Frédéric Oberti8, Aurélie Plessier9, Victor De Ledinghen10, Nathalie Ganne-Carrié11, Nicolas Carbonell12, Vanessa Rousseau13, Agnès Sommet13, Jean Marie Péron1, Jean Pierre Vinel1. 1. University Hospital of Toulouse and Toulouse III Paul Sabatier University, Toulouse, France (C.B., J.M.P., J.P.V.). 2. Groupe Hospitalier Pitié-Salpêtrière, Paris, France (D.T.). 3. Centre d'Investigation Clinique de Rennes, Rennes, France (C.J.). 4. Centre Hospitalier Universitaire de Nantes, Nantes, France (I.A.). 5. Trousseau University Hospital of Tours, Tours, France (L.D.M.). 6. Centre Hospitalier Universitaire de Lille, Lille, France (S.D.). 7. Centre Hospitalo-Universitaire Timone, Marseille, France (P.B.). 8. Centre Hospitalier Universitaire d'Angers, Angers, France (F.O.). 9. Beaujon Hospital, Clichy, France (A.P.). 10. Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France (V.D.). 11. Hôpitaux Universitaires Paris Seine-Saint-Denis, Bondy, and Université Paris 13, Sorbonne Paris Cité et INSERM UMR 1162, Paris, France (N.G.). 12. Hôpital Saint-Antoine, Paris, France (N.C.). 13. Toulouse University Hospital, Toulouse, France (V.R., A.S.).
Abstract
BACKGROUND: The efficacy of rifaximin in the secondary prevention of overt hepatic encephalopathy (HE) is well documented, but its effectiveness in preventing a first episode in patients after transjugular intrahepatic portosystemic shunt (TIPS) has not been established. OBJECTIVE: To determine whether rifaximin prevents overt HE after TIPS compared with placebo. DESIGN: Randomized, double-blind, multicenter, placebo-controlled trial. (ClinicalTrials.gov: NCT02016196). PARTICIPANTS: 197 patients with cirrhosis undergoing TIPS for intractable ascites or prevention of variceal rebleeding. INTERVENTION: Patients were randomly assigned to receive rifaximin (600 mg twice daily) or placebo, beginning 14 days before TIPS and continuing for 168 days after the procedure. MEASUREMENTS: The primary efficacy end point was incidence of overt HE within 168 days after the TIPS procedure. RESULTS: An episode of overt HE occurred in 34% (95% CI, 25% to 44%) of patients in the rifaximin group (n = 93) and 53% (CI, 43% to 63%) in the placebo group (n = 93) during the postprocedure period (odds ratio, 0.48 [CI, 0.27 to 0.87]). Neither the incidence of adverse events nor transplant-free survival was significantly different between the 2 groups. LIMITATIONS: The study's conclusion applies mainly to patients with alcoholic cirrhosis, who made up the study population. The potential benefit of rifaximin 6 months after TIPS and beyond remains to be investigated. CONCLUSION: In patients with cirrhosis treated withTIPS, rifaximin was well tolerated and reduced the risk for overt HE. Rifaximin should therefore be considered for prophylaxis of post-TIPS HE. PRIMARY FUNDING SOURCE: French Public Health Ministry.
RCT Entities:
BACKGROUND: The efficacy of rifaximin in the secondary prevention of overt hepatic encephalopathy (HE) is well documented, but its effectiveness in preventing a first episode in patients after transjugular intrahepatic portosystemic shunt (TIPS) has not been established. OBJECTIVE: To determine whether rifaximin prevents overt HE after TIPS compared with placebo. DESIGN: Randomized, double-blind, multicenter, placebo-controlled trial. (ClinicalTrials.gov: NCT02016196). PARTICIPANTS: 197 patients with cirrhosis undergoing TIPS for intractable ascites or prevention of variceal rebleeding. INTERVENTION: Patients were randomly assigned to receive rifaximin (600 mg twice daily) or placebo, beginning 14 days before TIPS and continuing for 168 days after the procedure. MEASUREMENTS: The primary efficacy end point was incidence of overt HE within 168 days after the TIPS procedure. RESULTS: An episode of overt HE occurred in 34% (95% CI, 25% to 44%) of patients in the rifaximin group (n = 93) and 53% (CI, 43% to 63%) in the placebo group (n = 93) during the postprocedure period (odds ratio, 0.48 [CI, 0.27 to 0.87]). Neither the incidence of adverse events nor transplant-free survival was significantly different between the 2 groups. LIMITATIONS: The study's conclusion applies mainly to patients with alcoholic cirrhosis, who made up the study population. The potential benefit of rifaximin 6 months after TIPS and beyond remains to be investigated. CONCLUSION: In patients with cirrhosis treated with TIPS, rifaximin was well tolerated and reduced the risk for overt HE. Rifaximin should therefore be considered for prophylaxis of post-TIPS HE. PRIMARY FUNDING SOURCE: French Public Health Ministry.
Authors: Justin R Boike; Bartley G Thornburg; Sumeet K Asrani; Michael B Fallon; Brett E Fortune; Manhal J Izzy; Elizabeth C Verna; Juan G Abraldes; Andrew S Allegretti; Jasmohan S Bajaj; Scott W Biggins; Michael D Darcy; Maryjane A Farr; Khashayar Farsad; Guadalupe Garcia-Tsao; Shelley A Hall; Caroline C Jadlowiec; Michael J Krowka; Jeanne Laberge; Edward W Lee; David C Mulligan; Mitra K Nadim; Patrick G Northup; Riad Salem; Joseph J Shatzel; Cathryn J Shaw; Douglas A Simonetto; Jonathan Susman; K Pallav Kolli; Lisa B VanWagner Journal: Clin Gastroenterol Hepatol Date: 2021-07-15 Impact factor: 13.576