GERDPhase 4NCT04028466
Effectiveness of Vonoprazan vs Omeprazole as Empiric Therapy for Gastroesophageal Reflux Disease (GERD) Patients Without Alarm Features
A Phase 4 study testing Vonoprazan and Omeprazole in people with GERD and Gastro Esophageal Reflux, run by St. Luke's Medical Center, Philippines at 1 site in Philippines.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- GERD, Gastro Esophageal Reflux
- What is being tested?
- Vonoprazan and Omeprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 1 sitePhilippines
- Study dates
- 26 May 2019to 30 Mar 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 14Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
Philippines1 site
St. Luke's Medical Center
Quezon City, National Capital Region, 1112
About this study
Official title: 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
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.
Read the 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.
- Conditions
- GERD, Gastro Esophageal Reflux
- Being tested
- Vonoprazan, Omeprazole
- Keywords
- GERD, gastro esophageal reflux, proton pump inhibitor, Potassium-Competitive Acid Blocker, H(+)-K(+)-Exchanging ATPase, Randomized Controlled Trial
- Medical subject headings
- Gastroesophageal Reflux
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VonoprazanDrug
Also called Investigational Arm
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
OmeprazoleDrug
Also called Control Arm
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Omeprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: day 14 of therapy
Secondary outcomes (9)
Proportion of partial responders at Day 3
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
Measured: day 3 of therapy
Proportion of partial responders at Day 7
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
Measured: day 7 of therapy
Proportion of partial responders at Day 14
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
Measured: day 14 of therapy
Proportion of nonresponders at Day 14
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
Measured: day 14 of therapy
Percent change in the symptom score from baseline (Vonoprazan Group) - Day 3
Difference in the symptom score from baseline using the FSSG questionnaire at each time point within Vonoprazan and omeprazole group; expressed in percentage
Measured: day 3 of therapy
Percent change in the symptom score from baseline (Vonoprazan Group) - Day 7
Difference in the symptom score from baseline using the FSSG questionnaire at each time point within Vonoprazan and omeprazole group; expressed in percentage
Measured: day 7 of therapy
Percent change in the symptom score from baseline (Vonoprazan Group) - Day 14
Difference in the symptom score from baseline using the FSSG questionnaire at each time point within Vonoprazan and omeprazole group; expressed in percentage
Measured: day 14 of therapy
Difference in percent change in the symptom score (between groups)
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
Measured: day 3, 7, and 14 of therapy
Number of Patients with Adverse Effects
Safety and frequency of adverse effects experienced by patients (nasopharyngitis, diarrhea, constipation, upper respiratory tract infection, gastroenteritis, eczema/allergy, hypergastrinemia)
Measured: Day 14 of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2019
- Study start26 May 2019
- Primary completion30 Mar 2020
- Study completion30 Mar 2020
Why it stopped: Budget for the study was withdrawn and discontinued
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for GERDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Pragmatic, Randomized, Single Blind Study
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Luke's Medical Center, Philippines
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nicodemus Ong, St. Luke's Medical Center, Philippines
- Investigators
- Nicodemus L Ong, MD, Principal investigator, Institute of Digestive and Liver Diseases, St. Luke's Medical Center, Quezon CitySherrie Isabel Q De Ocampo, MD, Principal investigator, Institute of Digestive and Liver Diseases, St. Luke's Medical Center, Quezon City
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04028466
- Sponsor's protocol ID
- RP 19-007
- Status last verified
- Nov 2023
- First submitted
- 6 Jul 2019
- Last updated
- 22 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Approval from the Institutional review board should be secured before IPD will be made available
Publications
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.
PubMed 16928254Cederberg 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.
PubMed 1291405Dammann HG, Burkhardt F. Pantoprazole versus omeprazole: influence on meal-stimulated gastric acid secretion. Eur J Gastroenterol Hepatol. 1999 Nov;11(11):1277-82.
PubMed 10563540Bytzer 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.
PubMed 16990197Peura 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.
PubMed 19523177Chong 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.
PubMed 12680476Furuta 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.
PubMed 15988117Katz 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.
PubMed 15298633Johnson DA, Katz PO. Nocturnal gastroesophageal reflux disease: issues, implications, and management strategies. Rev Gastroenterol Disord. 2008 Spring;8(2):98-108.
PubMed 18641592Fass 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.
PubMed 19392864Kusano 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.
PubMed 15565409Oshima 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.
PubMed 29739175Ashida 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.
PubMed 26559637Iwakiri 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. Ther Adv Gastroenterol. 2017 Jun;10(6):439-451. doi: 10.1177/1756283X17705329. Epub 2017 Apr 25.
PubMed 28567114Shinozaki 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.
PubMed 28894571
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04028466
- Acronym / sponsor ID
- RP 19-007
- Conditions
- GERD, Gastro Esophageal Reflux
- Keywords
- GERD, gastro esophageal reflux, proton pump inhibitor, Potassium-Competitive Acid Blocker, H(+)-K(+)-Exchanging ATPase, Randomized Controlled Trial
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Budget for the study was withdrawn and discontinued
- Enrolment
- 82 participants (actual)
- Lead sponsor
- St. Luke's Medical Center, PhilippinesUniversity, hospital or other
- Study start
- 26 May 2019 (actual)
- Primary completion
- 30 Mar 2020 (actual)
- Study completion
- 30 Mar 2020 (actual)
- First posted
- 22 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Pragmatic, Randomized, Single Blind Study
| Arm | Type | Receives |
|---|---|---|
| Vonoprazan | Experimental | Drug: VonoprazanPatients will be randomized to receiving vonoprazan, which will be taken 30 minutes before the first meal of the day for 14 days |
| Omeprazole | Active comparator | Drug: OmeprazolePatients will be randomized to receiving omeprazole, which will be taken 30 minutes before the first meal of the day for 14 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VonoprazanAlso: Investigational ArmPatients 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 | Drug | Vonoprazan |
| OmeprazoleAlso: Control ArmPatients 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 | Drug | Omeprazole |
Primary outcome
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
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
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
9 secondary outcomes
Proportion of partial responders at Day 3
Time frame: day 3 of therapy
Proportion of partial responders at Day 7
Time frame: day 7 of therapy
Proportion of partial responders at Day 14
Time frame: day 14 of therapy
Proportion of nonresponders at Day 14
Time frame: day 14 of therapy
Percent change in the symptom score from baseline (Vonoprazan Group) - Day 3
Time frame: day 3 of therapy
Percent change in the symptom score from baseline (Vonoprazan Group) - Day 7
Time frame: day 7 of therapy
Percent change in the symptom score from baseline (Vonoprazan Group) - Day 14
Time frame: day 14 of therapy
Difference in percent change in the symptom score (between groups)
Time frame: day 3, 7, and 14 of therapy
Number of Patients with Adverse Effects
Time frame: Day 14 of therapy
Results and safety
The study was stopped early (reason given: Budget for the study was withdrawn and discontinued). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2023.
- Background: PubMed 16928254Vakil 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.
- Background: PubMed 1291405Cederberg 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.
- Background: PubMed 10563540Dammann HG, Burkhardt F. Pantoprazole versus omeprazole: influence on meal-stimulated gastric acid secretion. Eur J Gastroenterol Hepatol. 1999 Nov;11(11):1277-82.
- Background: PubMed 16990197Bytzer 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.
- Background: PubMed 19523177Peura 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.
- Background: PubMed 12680476Chong 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.
- Background: PubMed 15988117Furuta 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.
- Background: PubMed 15298633Katz 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.
- Background: PubMed 18641592Johnson DA, Katz PO. Nocturnal gastroesophageal reflux disease: issues, implications, and management strategies. Rev Gastroenterol Disord. 2008 Spring;8(2):98-108.
- Background: PubMed 19392864Fass 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.
- Background: PubMed 15565409Kusano 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.
- Results publication: PubMed 29739175Oshima 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.
- Individual participant dataSharing planned: Undecided. Approval from the Institutional review board should be secured before IPD will be made available
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicodemus L Ong, MD principal investigator
Institute of Digestive and Liver Diseases, St. Luke's Medical Center, Quezon City
Sherrie Isabel Q De Ocampo, MD principal investigator
Institute of Digestive and Liver Diseases, St. Luke's Medical Center, Quezon City
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Vonoprazan and Omeprazole in people with GERD and Gastro Esophageal Reflux, run by St. Luke's Medical Center, Philippines at 1 site in Philippines.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Philippines. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Budget for the study was withdrawn and discontinued). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of asymptomatic patients at Day 3 (time frame: day 3 of therapy). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04028466, which also lists 17 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2023.