1.
Vonoprazan prevents low-dose aspirin-associated ulcer recurrence: randomised phase 3 study.
Kawai, T, Oda, K, Funao, N, Nishimura, A, Matsumoto, Y, Mizokami, Y, Ashida, K, Sugano, K
Gut. 2018;(6):1033-1041
-
-
Free full text
-
Abstract
OBJECTIVE Compare efficacy and safety of vonoprazan and lansoprazole for secondary prevention of low-dose aspirin (LDA)-associated peptic ulcers in a 24-week study and long-term extension therapy in separate study. DESIGN Double-blind, randomised, non-inferiority study; single-blind extension study at 104 Japanese sites, including 621 patients (439 in extension) with a history of peptic ulcers who required long-term LDA therapy. Randomised (1:1:1, computer generated) patients received lansoprazole 15 mg (n=217), vonoprazan 10 mg (n=202) or vonoprazan 20 mg (n=202) once daily for 24 weeks (double blind) and ≤2 years (extension). The following measurements were made: 24-week (primary outcome; double blind) and 12-week peptic ulcer recurrence rate, 24-week GI bleeding rate, cumulative incidences of peptic ulcer recurrence and GI bleeding, treatment-emergent adverse events, laboratory results, serum gastrin and pepsinogen I/II concentrations. RESULTS The 24-week peptic ulcer recurrence rate was 2.8%, 0.5% and 1.5% in the lansoprazole 15 mg, vonoprazan 10 mg and vonoprazan 20 mg groups, respectively. Vonoprazan was non-inferior (Farrington and Manning test: margin 8.7%, significance level 2.5%) to lansoprazole. In the post hoc analyses of the extension study, peptic ulcer recurrence rates were significantly lower with vonoprazan 10 mg (log-rank test, P=0.039), but not vonoprazan 20 mg (P=0.260), compared with lansoprazole 15 mg. GI bleeding rates were higher with lansoprazole compared with two doses of vonoprazan in both 24-week study and extension study. CONCLUSION Vonoprazan (10 and 20 mg) was as effective as lansoprazole (15 mg) in preventing peptic ulcer recurrence during LDA therapy, had a similar long-term safety profile and was well tolerated. TRIAL REGISTRATION NUMBERS NCT01452763; NCT01456247.
2.
Effects of Long-Term Walnut Supplementation on Body Weight in Free-Living Elderly: Results of a Randomized Controlled Trial.
Bitok, E, Rajaram, S, Jaceldo-Siegl, K, Oda, K, Sala-Vila, A, Serra-Mir, M, Ros, E, Sabaté, J
Nutrients. 2018;(9)
Abstract
Objective: To assess the effects of chronic walnut consumption on body weight and adiposity in elderly individuals. Methods: The Walnuts and Healthy Aging study is a dual-center (Barcelona, Spain and Loma Linda University (LLU)), 2-year randomized parallel trial. This report concerns only the LLU cohort. Healthy elders (mean age 69 year, 67% women) were randomly assigned to walnut (n = 183) or control diets (n = 173). Subjects in the walnut group received packaged walnuts (28⁻56 g/day), equivalent to ≈15% of daily energy requirements, to incorporate into their habitual diet, while those in the control group abstained from walnuts. Adiposity was measured periodically, and data were adjusted for in-trial changes in self-reported physical activity. Results: After 2 years, body weight significantly decreased (p = 0.031), while body fat significantly increased (p = 0.0001). However, no significant differences were observed between the control and walnut groups regarding body weight (-0.6 kg and -0.4 kg, respectively, p = 0.67) or body fat (+0.9% and +1.3%, respectively, p = 0.53). Lean body mass, waist circumference, and waist-to-hip ratio remained essentially unchanged. Sensitivity analyses were consistent with the findings of primary analysis. Conclusion: Our findings indicate that walnuts can be incorporated into the daily diet of healthy elders without concern for adverse effects on body weight or body composition.
3.
Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study.
Mizokami, Y, Oda, K, Funao, N, Nishimura, A, Soen, S, Kawai, T, Ashida, K, Sugano, K
Gut. 2018;(6):1042-1051
-
-
Free full text
-
Abstract
OBJECTIVE To assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use. DESIGN A phase 3, 24-week, multicenter, randomised, double-blind (DB), active-controlled study, followed by a phase 3, ≥28 week, multicenter, single-blind, parallel-group extension study (EXT) in outpatients (n=642) receiving long-term NSAID therapy who are at risk of PU recurrence. The patients received vonoprazan (10 mg or 20 mg) or lansoprazole 15 mg once daily. For DB, non-inferiority of the proportion of patients with recurrent PU within 24 weeks was analysed by Farrington and Manning test (significance level 2.5%, non-inferiority margin 8.3%; primary endpoint), recurrent PU within 12 weeks, bleeding and time-to-event of PU (secondary endpoint) and treatment-emergent adverse events (TEAEs). For EXT, TEAEs (primary endpoint), recurrent PU and safety (secondary) were assessed up to 104 weeks for patients in the extension study. RESULTS The non-inferiority of vonoprazan 10 mg and 20 mg to lansoprazole 15 mg was verified (percentage difference -2.2%,95% CI -6.2% to 1.8%, p<0.001; -2.1%,95% CI -6.1% to 2.0%, p<0.001, respectively). The proportion of patients with endoscopically confirmed recurrent PU within 24 weeks was 3.3%, 3.4% and 5.5%, for vonoprazan 10 mg, 20 mg and lansoprazole 15 mg, respectively. No significant safety concerns were identified. CONCLUSION The non-inferiority of vonoprazan (10 and 20 mg) was verified in patients receiving long-term NSAIDs in DB; it was effective and well tolerated in EXT for longer than 1 year, with a safety profile similar to lansoprazole (15 mg). TRIAL REGISTRATION NUMBERS NCT01452750, NCT01456260; Results.