Effectiveness of Vonoprazan vs Omeprazole as Empiric Therapy for Gastroesophageal Reflux Disease (GERD) Patients Without Alarm Features

NCT04028466 | Terminated Phase 4 DMC

• 1 other identifier: RP 19-007
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

Brief Summary

Gastroesophageal reflux disease is a commonly encountered disorder in daily practice. Proton pump inhibitor therapy has been the cornerstone of treatment for decades. Although it has been proven to be highly effective, there is still room for improvement. A local study showed that only 57.3% of subjects are asymptomatic after 4 weeks treatment with rabeprazole. Recently a new drug was developed with better absorption, higher bioavailability, more sustained increased pH in the stomach and more targeted action to the H-K ATPase pump. Vonoprazan, belongs to a new class of acid suppressant medications, the potassium-competitive acid blocker (P-CAB). Vonoprazan has been studied and used successfully in Japan for H pylori eradication therapy, GERD, gastric and duodenal ulcers with favorable safety profile. However, to the author's knowledge, no study yet exists comparing vonoprazan to a proton pump inhibitor in the treatment of GERD outside Japan. This study aims to determine whether vonoprazan is superior to omeprazole in relieving symptoms in treatment-naïve adult patients with GERD.

Conditions

GERD; Gastro Esophageal Reflux

Keywords

GERD; gastro esophageal reflux; proton pump inhibitor; Potassium-Competitive Acid Blocker; H(+)-K(+)-Exchanging ATPase; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (3)

• Proportion of asymptomatic patients at Day 3

  Asymptomatic patients is defined as a patient being free of symptoms of heartburn or acid regurgitation according to FSSG questionnaire (score \<8) Expressed in percentage

  day 3 of therapy

• Proportion of asymptomatic patients at Day 7

  Asymptomatic patients is defined as a patient being free of symptoms of heartburn or acid regurgitation according to FSSG questionnaire (score \<8) Expressed in percentage

  day 7 of therapy

• Proportion of asymptomatic patients at Day 14

  Asymptomatic patients is defined as a patient being free of symptoms of heartburn or acid regurgitation according to FSSG questionnaire (score \<8) Expressed in percentage

  day 14 of therapy

Secondary Outcomes (9)

• Proportion of partial responders at Day 3

  day 3 of therapy

• Proportion of partial responders at Day 7

  day 7 of therapy

• Proportion of partial responders at Day 14

  day 14 of therapy

• Proportion of nonresponders at Day 14

  day 14 of therapy

• Percent change in the symptom score from baseline (Vonoprazan Group) - Day 3

  day 3 of therapy

Study Arms (2)

Vonoprazan

EXPERIMENTAL

Patients will be randomized to receiving vonoprazan, which will be taken 30 minutes before the first meal of the day for 14 days

Drug: Vonoprazan

Omeprazole

ACTIVE COMPARATOR

Patients will be randomized to receiving omeprazole, which will be taken 30 minutes before the first meal of the day for 14 days

Drug: Omeprazole

Interventions

Vonoprazan DRUG

Patients will be randomized to receiving vonoprazan 20mg tablet or omeprazole 40mg capsule, either of which will be taken 30 minutes before the first meal of the day for 14 days

Also known as: Investigational Arm

Vonoprazan

Omeprazole DRUG

Patients will be randomized to receving vonoprazan 20mg tablet or omeprazole 40mg capsule, either of which will be taken 30 minutes before the first meal of the day for 14 days

Also known as: Control Arm

Omeprazole

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Adult patients with clinically diagnosed with Gastroesophageal Reflux Disease (GERD) without alarm features (heartburn and acid regurgitation)
• Age more than 18 years at the time of written consent
• Those who provide written consent with their own free will
• Both treatment naïve and treatment experienced patients will be included. Treatment experienced patients should not be taking any proton pump inhibitors for 2 weeks to allow for washout period.

You may not qualify if:

• Patients that have alarm features as defined by the Philippines Guidelines for GERD (dysphagia, odynophagia, weight loss, anemia, hematemesis, family history of esophageal adenocarcinoma, nocturnal choking, abdominal mass, recurrent/frequent vomiting, chest pain)
• Patients with atypical GERD symptoms (cough, laryngitis, chest pain, etc.)
• Patients already taking proton pump inhibitors for the past 2 weeks
• Patients who scored less than 8 on the FSSG questionnaire
• Patients who have undergone gastroesophageal surgery
• Patients who are poorly compliant to medications
• allergy to PPI or vonoprazan
• With serious comorbidities, such as but not limited to: heart failure, renal failure, malignancy or hepatic failure
• Pregnant, breastfeeding or possibly pregnant
• Patients that would not provide consent
• Patients who are unable to complete the FSSG Questionnaire independently
• Patients who are unable to follow up at designated periods
• Patients taking rilpivirine or atazanavir.
• Patients with elevated baseline liver function tests (more than twice the upper limit of normal)

Sponsors & Collaborators

• St. Luke's Medical Center, Philippines: lead

Study Sites (1)

St. Luke's Medical Center

Quezon City, National Capital Region, 1112, Philippines

Location

Related Publications (17)

• Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R; Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006 Aug;101(8):1900-20; quiz 1943. doi: 10.1111/j.1572-0241.2006.00630.x.

  PMID: 16928254 BACKGROUND

• Cederberg C, Lind T, Rohss K, Olbe L. Comparison of once-daily intravenous and oral omeprazole on pentagastrin-stimulated acid secretion in duodenal ulcer patients. Digestion. 1992;53(3-4):171-8. doi: 10.1159/000200992.

  PMID: 1291405 BACKGROUND

• Dammann HG, Burkhardt F. Pantoprazole versus omeprazole: influence on meal-stimulated gastric acid secretion. Eur J Gastroenterol Hepatol. 1999 Nov;11(11):1277-82.

  PMID: 10563540 BACKGROUND

• Bytzer P, Morocutti A, Kennerly P, Ravic M, Miller N; ROSE Trial Investigators. Effect of rabeprazole and omeprazole on the onset of gastro-oesophageal reflux disease symptom relief during the first seven days of treatment. Scand J Gastroenterol. 2006 Oct;41(10):1132-40. doi: 10.1080/00365520600615781.

  PMID: 16990197 BACKGROUND

• Peura DA, Riff DS, Snoddy AM, Fennerty MB. Clinical trial: lansoprazole 15 or 30 mg once daily vs. placebo for treatment of frequent nighttime heartburn in self-treating subjects. Aliment Pharmacol Ther. 2009 Sep 1;30(5):459-68. doi: 10.1111/j.1365-2036.2009.04064.x. Epub 2009 Jun 11.

  PMID: 19523177 BACKGROUND

• Chong E, Ensom MH. Pharmacogenetics of the proton pump inhibitors: a systematic review. Pharmacotherapy. 2003 Apr;23(4):460-71. doi: 10.1592/phco.23.4.460.32128.

  PMID: 12680476 BACKGROUND

• Furuta T, Shirai N, Sugimoto M, Nakamura A, Hishida A, Ishizaki T. Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapies. Drug Metab Pharmacokinet. 2005 Jun;20(3):153-67. doi: 10.2133/dmpk.20.153.

  PMID: 15988117 BACKGROUND

• Katz PO, Castell DO, Chen Y, Andersson T, Sostek MB. Intragastric acid suppression and pharmacokinetics of twice-daily esomeprazole: a randomized, three-way crossover study. Aliment Pharmacol Ther. 2004 Aug 15;20(4):399-406. doi: 10.1111/j.1365-2036.2004.02079.x.

  PMID: 15298633 BACKGROUND

• Johnson DA, Katz PO. Nocturnal gastroesophageal reflux disease: issues, implications, and management strategies. Rev Gastroenterol Disord. 2008 Spring;8(2):98-108.

  PMID: 18641592 BACKGROUND

• Fass R, Chey WD, Zakko SF, Andhivarothai N, Palmer RN, Perez MC, Atkinson SN. Clinical trial: the effects of the proton pump inhibitor dexlansoprazole MR on daytime and nighttime heartburn in patients with non-erosive reflux disease. Aliment Pharmacol Ther. 2009 Jun 15;29(12):1261-72. doi: 10.1111/j.1365-2036.2009.04013.x. Epub 2009 Apr 8.

  PMID: 19392864 BACKGROUND

• Kusano M, Shimoyama Y, Sugimoto S, Kawamura O, Maeda M, Minashi K, Kuribayashi S, Higuchi T, Zai H, Ino K, Horikoshi T, Sugiyama T, Toki M, Ohwada T, Mori M. Development and evaluation of FSSG: frequency scale for the symptoms of GERD. J Gastroenterol. 2004 Sep;39(9):888-91. doi: 10.1007/s00535-004-1417-7.

  PMID: 15565409 BACKGROUND

• Oshima T, Miwa H. Potent Potassium-competitive Acid Blockers: A New Era for the Treatment of Acid-related Diseases. J Neurogastroenterol Motil. 2018 Jul 30;24(3):334-344. doi: 10.5056/jnm18029.

  PMID: 29739175 RESULT

• Ashida K, Sakurai Y, Hori T, Kudou K, Nishimura A, Hiramatsu N, Umegaki E, Iwakiri K. Randomised clinical trial: vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis. Aliment Pharmacol Ther. 2016 Jan;43(2):240-51. doi: 10.1111/apt.13461. Epub 2015 Nov 11.

  PMID: 26559637 RESULT

• Iwakiri K, Sakurai Y, Shiino M, Okamoto H, Kudou K, Nishimura A, Hiramatsu N, Umegaki E, Ashida K. A randomized, double-blind study to evaluate the acid-inhibitory effect of vonoprazan (20 mg and 40 mg) in patients with proton-pump inhibitor-resistant erosive esophagitis. Therap Adv Gastroenterol. 2017 Jun;10(6):439-451. doi: 10.1177/1756283X17705329. Epub 2017 Apr 25.

  PMID: 28567114 RESULT

• Shinozaki S, Osawa H, Hayashi Y, Sakamoto H, Kobayashi Y, Lefor AK, Yamamoto H. Vonoprazan 10 mg daily is effective for the treatment of patients with proton pump inhibitor-resistant gastroesophageal reflux disease. Biomed Rep. 2017 Sep;7(3):231-235. doi: 10.3892/br.2017.947. Epub 2017 Jul 20.

  PMID: 28894571 RESULT

• Kinoshita Y, Sakurai Y, Shiino M, Kudou K, Nishimura A, Miyagi T, Iwakiri K, Umegaki E, Ashida K. Evaluation of the Efficacy and Safety of Vonoprazan in Patients with Nonerosive Gastroesophageal Reflux Disease: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study. Curr Ther Res Clin Exp. 2016 Dec 21;81-82:1-7. doi: 10.1016/j.curtheres.2016.12.001. eCollection 2016.

  PMID: 28119763 RESULT

• Mori H, Suzuki H. Role of Acid Suppression in Acid-related Diseases: Proton Pump Inhibitor and Potassium-competitive Acid Blocker. J Neurogastroenterol Motil. 2019 Jan 31;25(1):6-14. doi: 10.5056/jnm18139.

  PMID: 30504527 RESULT

MeSH Terms

Conditions

Gastroesophageal Reflux

Interventions

1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine; Omeprazole

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Nicodemus L Ong, MD

  Institute of Digestive and Liver Diseases, St. Luke's Medical Center, Quezon City

  PRINCIPAL INVESTIGATOR

• Sherrie Isabel Q De Ocampo, MD

  Institute of Digestive and Liver Diseases, St. Luke's Medical Center, Quezon City

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Randomized, Single Blind Study. Only primary investigators are blinded. the primary investigator also are the outcome assessors
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Fellow and Principal Investigator, Institute of Digestlve and Liver Diseases

Model Details: Pragmatic, Randomized, Single Blind Study

Study Record Dates

• First Submitted: July 6, 2019
• First Posted: July 22, 2019
• Study Start: May 26, 2019
• Primary Completion: March 30, 2020
• Study Completion: March 30, 2020
• Last Updated: November 22, 2023

Record last verified: 2023-11

Locations

PH (1)