IW-3718 Reduces Heartburn Severity in Patients With Refractory Gastroesophageal Reflux Disease in a Randomized Trial
| Autor: | Yan Chen, Amy M. Gates, Robert S. Mittleman, James Z. Shao, Nimish Vakil, Michael F. Vaezi, Ronnie Fass, Lara Lane, Mark G. Currie, Michael Hall, David S. Reasner |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Time Factors medicine.drug_class Colesevelam Hydrochloride Proton-pump inhibitor Placebo Gastroenterology Severity of Illness Index law.invention Bile Acids and Salts 03 medical and health sciences Young Adult 0302 clinical medicine Randomized controlled trial Double-Blind Method Heartburn law Internal medicine medicine Clinical endpoint Esophagitis Humans Adverse effect Aged Aged 80 and over Hepatology business.industry Remission Induction Proton Pump Inhibitors Middle Aged medicine.disease United States 030104 developmental biology Treatment Outcome Delayed-Action Preparations GERD Gastroesophageal Reflux 030211 gastroenterology & hepatology Drug Therapy Combination Female medicine.symptom business |
| Zdroj: | Gastroenterology. 158(8) |
| ISSN: | 1528-0012 |
| Popis: | Background & Aims Refractory gastroesophageal reflux disease (GERD) reduces quality of life and creates significant financial burden on the health care system. Approximately 30% of patients with GERD who receive label-dose proton pump inhibitors (PPIs) still have symptoms. We performed a trial to evaluate the efficacy and safety of IW-3718, a bile acid sequestrant, as an adjunct to PPI therapy. Methods We performed a multicenter, double-blind, placebo-controlled trial, from March 2016 through April 2017, of 280 patients with confirmed GERD. The patients, stratified by esophagitis status, were randomly assigned (1:1:1:1) to groups given placebo or IW-3718 (500, 1000, or 1500 mg) twice daily, with ongoing label-dose PPI. The primary endpoint was percent change from baseline to week 8 in weekly heartburn severity score. We also analyzed percent change from baseline to week 8 in weekly regurgitation frequency score. Results Mean changes from baseline to week 8 in weekly heartburn severity scores were reductions of 46.0% in the placebo group, 49.0% in the 500 mg group, 55.1% in the 1000 mg group, and 58.0% in the 1500 mg IW-3718 group (dose-response P = .02). The treatment difference was 11.9% between the 1500 mg IW-3718 and placebo groups (P = .04, analysis of covariance). The mean change in weekly regurgitation frequency score from baseline to week 8 in the 1500 mg IW-3718 vs placebo groups was a reduction of 17.5% (95% confidence interval, reductions of 31.4% to 3.6%). The most common adverse event was constipation (in 8.1% of patients receiving IW-3718 and 7.1% of patients receiving placebo). There were no drug-related serious adverse events. Conclusions In a randomized trial of patients with refractory GERD, adding 1500 mg IW-3718 to label-dose PPIs significantly reduced heartburn symptoms compared with adding placebo. Regurgitation symptoms also decreased. IW-3718 was well tolerated. ( ClinicalTrials.gov , Number: NCT02637557 ) |
| Databáze: | OpenAIRE |
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