- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04028466
Effectiveness of Vonoprazan vs Omeprazole as Empiric Therapy for Gastroesophageal Reflux Disease (GERD) Patients Without Alarm Features
Effectiveness of Vonoprazan vs Omeprazole as Empiric Therapy for Gastroesophageal Reflux Disease (GERD) Patients Without Alarm Features in a Primary Care Setting: A Pragmatic, Randomized, Single Blind Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Gastroesophageal Reflux Disease (GERD) is globally defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. The Philippine Clinical Practice Guideline on the Diagnosis and Treatment of GERD defined is as a condition resulting from recurrent backflow of gastric contents into the esophagus and adjacent structures causing troublesome symptoms and/or tissue injury. It is a commonly encountered disorder in the clinics and daily practice. A clinical diagnosis of GERD is acceptable with typical symptoms of acid regurgitation and/or heartburn is present. The Philippine guidelines state that empiric therapy can be started in GERD patients without alarm features and don't require further laboratory exam or workup. The guideline recommends standard dose proton pump inhibitor (PPI) therapy once daily for 8 weeks as cornerstone for treatment.
Proton pump inhibitor (PPI) therapy has been used as first line therapy of reflux symptoms for more than a decade. Even though it has been proven to be highly effective for reflux symptoms, there are still unaddressed issues. A local study by Lontok et al in 2013 evaluated response of GERD patients to rabeprazole 20mg once daily using a locally validated Frequency Scale of Symptoms of GERD (FSSG) in a primary care setting. Their study showed that a 4 week rabeprazole therapy resulting in complete resolution of individual symptoms ranging from 81.9-90.3%, with only 57.3% of all subjects being completely asymptomatic at the end of treatment. Proton pump inhibitors also have unmet issues needing improvement. PPIs usually takes 5 days for their maximal effect. Because of their slow onset of action, a significant number of patients are not sufficiently relieved after the first dose of PPI. Approximately half of patients still have symptoms after 3 days of treatment. PPIs are influenced by the cytochrome P450 (CYP) 2C19 polymorphism, with rapid metabolizers having the lowest intragastric pH compared with slow metabolizers. PPIs are also not sufficiently effective in controlling nocturnal heartburn symptoms because overnight recovery of gastric acid is frequently seen, therefore causing loss of sleep and health-related reductions in quality of life.
Recently, a new drug that promises better pharmacokinetic and pharmacodynamics properties was developed. Its use has been mostly in Japan for the past 2 years. Vonoprazan, is a novel, potassium-competitive acid blocker (P-CAB) that binds and inhibits H-K ATPase, the final step in acid secretion from the parietal cells of the stomach. It can inhibit the proton pump in both acidic and neutral environments with high affinity. The drug is retained for a long time inside the parietal cells and can inhibit H-K ATPase that is activated by further stimulation of acid secretion. Vonoprazan offers the advantage of not being required to be taken before meals, compared to conventional PPIs where 30 minutes before a meal is required, and is unaffected by the CYP2C19 polymorphism. Vonoprazan is also effectively absorbed and quickly accumulates in parietal cells, therefore, acid inhibition is more pronounced after the first dose of vonoprazan, compared to conventional PPIs where it usually takes 3-5 days for maximal effect. Vonoprazan is therefore, a stronger acid blocker that has rapid, stable and longer-lasting effects. Of the author's knowledge only 2 large scale randomized controlled trial have been done with vonoprazan, both these studies were done in Japan and focus only on those with erosive esophagitis. Vonoprazan has been showed to be effective and noninferior to lansoprazole for curing erosive esophagitis, as well as PPI resistant erosive esophagitis, with healing rates more pronounced for Grade C and D erosive esophagitis. Other studies on the use of vonoprazan for GERD have been done only in Japan, and comprised of noninferiority and small retrospective open label trials.
When vonoprazan is used for short term acid suppression, there are no problematic side effects. Treatment emergent adverse events irrespective of causal relationship to study medication are nasopharyngitis, diarrhea, constipation, upper respiratory infection, fall, gastroenteritis and eczema. Most of these treatment emergent adverse events were classified as mild in intensity. Studies are ongoing in Japan to assess the long term safety and efficacy of vonoprazan
. The Philippine Clinical Practice Guideline for GERD recommends locally-validated standardized questionnaire to assess treatment response to GERD. Commonly used questionnaires in the Philippines are the Frequency Scale for Severity of GERD (FSSG) and the Gastroesophageal Reflux Disease Questionnaire (GERDQ); both have undergone local validation studies. FSSG has been shown to correlate with endoscopic severity of GERD and assess response to proton pump inhibitor therapy.2 The FSSG comprises 12 questions where patients would rate individual symptoms as never (0% of the time), occasionally (around 30% of the time), sometimes (50%), often (70%) or always (100%). GERD is diagnosed if the score is more than 8, with sensitivity of 62%, specificity of 59% and accuracy of 60% for endoscopic diagnosis of esophagitis.
Vonoprazan was just recently introduced to the Philippine market recently. Whether or not this drug may replace conventional PPIs as first line therapy remains to be determined. This study aims to determine whether vonoprazan is superior to omeprazole in treating treatment-naïve adult patients with GERD. Data from this study will help formulate policies and recommendations on the treatment of GERD, as well as formulate new treatment strategies for patients with GERD.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Nicodemus L Ong, MD
- Phone Number: +639176791018
- Email: nico.ongmd@yahoo.com
Study Contact Backup
- Name: Sherrie Isabel Q De Ocampo, MD
- Phone Number: 09338555954
- Email: sherrieq@hotmail.com
Study Locations
-
-
National Capital Region
-
Quezon City, National Capital Region, Philippines, 1112
- St. Luke's Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Vonoprazan
Patients will be randomized to receiving vonoprazan, which will be taken 30 minutes before the first meal of the day for 14 days
|
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
Other Names:
|
Active Comparator: Omeprazole
Patients will be randomized to receiving omeprazole, which will be taken 30 minutes before the first meal of the day for 14 days
|
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
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of asymptomatic patients at Day 3
Time Frame: day 3 of therapy
|
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
Time Frame: day 7 of therapy
|
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
Time Frame: day 14 of therapy
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of partial responders at Day 3
Time Frame: day 3 of therapy
|
Partial responder are patients who still have GERD symptoms, but with partial improvement on reevaluation using the FSSG questionnaire; patients with at least 50% reduction from the baseline FSSG score Expressed in percentage
|
day 3 of therapy
|
Proportion of partial responders at Day 7
Time Frame: day 7 of therapy
|
Partial responder are patients who still have GERD symptoms, but with partial improvement on reevaluation using the FSSG questionnaire; patients with at least 50% reduction from the baseline FSSG score Expressed in percentage
|
day 7 of therapy
|
Proportion of partial responders at Day 14
Time Frame: day 14 of therapy
|
Partial responder are patients who still have GERD symptoms, but with partial improvement on reevaluation using the FSSG questionnaire; patients with at least 50% reduction from the baseline FSSG score Expressed in percentage
|
day 14 of therapy
|
Proportion of nonresponders at Day 14
Time Frame: day 14 of therapy
|
Nonresponders are patients who reported no significant improvement in symptoms with treatment; patients with less than 50% reduction from the baseline FSSG score Expressed in percentage
|
day 14 of therapy
|
Percent change in the symptom score from baseline (Vonoprazan Group) - Day 3
Time Frame: day 3 of therapy
|
Difference in the symptom score from baseline using the FSSG questionnaire at each time point within Vonoprazan and omeprazole group; expressed in percentage
|
day 3 of therapy
|
Percent change in the symptom score from baseline (Vonoprazan Group) - Day 7
Time Frame: day 7 of therapy
|
Difference in the symptom score from baseline using the FSSG questionnaire at each time point within Vonoprazan and omeprazole group; expressed in percentage
|
day 7 of therapy
|
Percent change in the symptom score from baseline (Vonoprazan Group) - Day 14
Time Frame: day 14 of therapy
|
Difference in the symptom score from baseline using the FSSG questionnaire at each time point within Vonoprazan and omeprazole group; expressed in percentage
|
day 14 of therapy
|
Difference in percent change in the symptom score (between groups)
Time Frame: day 3, 7, and 14 of therapy
|
Difference in the percent change of the FSSG score between groups will be analyzed using independent T test or Mann-Whitney U test between vonoprazan and omeprazole groups at one point in time
|
day 3, 7, and 14 of therapy
|
Number of Patients with Adverse Effects
Time Frame: Day 14 of therapy
|
Safety and frequency of adverse effects experienced by patients (nasopharyngitis, diarrhea, constipation, upper respiratory tract infection, gastroenteritis, eczema/allergy, hypergastrinemia)
|
Day 14 of therapy
|
Collaborators and Investigators
Investigators
- Principal Investigator: 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
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- Dammann HG, Burkhardt F. Pantoprazole versus omeprazole: influence on meal-stimulated gastric acid secretion. Eur J Gastroenterol Hepatol. 1999 Nov;11(11):1277-82.
- 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.
- 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.
- 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.
- 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.
- Johnson DA, Katz PO. Nocturnal gastroesophageal reflux disease: issues, implications, and management strategies. Rev Gastroenterol Disord. 2008 Spring;8(2):98-108.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- RP 19-007
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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