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
Phase: PHASE4
Conditions: GERD, Gastro Esophageal Reflux
Sponsor: St. Luke's Medical Center, Philippines

Protocol Version 10 dated 15 December 2019 
 
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R&B Form No. 1A 
St. Luke’s Medical Center 
RESEARCH AND BIOTECHNOLOGY 
 
CLINICAL RESEARCH PROPOSAL 
 
 
RESEARCH 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 
 
 
  
INVESTIGATORS: 
             
Name & Signature  
   
  Unit/Position 
Project Leader/s: 
      NICODEMUS ONG, MD  
        Gastroenterology/FELLOW 
 
 
 
 
 
Co-Project Leader/s: SHERRIE ISABEL DE OCAMPO, MD  Gastroenterology/CONSULTANT 
 
Institute/Department: INSTITUTE OF DIGESTIVE AND LIVER DISEASES 
 
 
1. BRIEF DESCRIPTION 
 
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. 
 
2. BACKGROUND 
 
Gastroesophageal Reflux Disease (GERD) is globally defined as a condition that develops when 
the reflux of stomach contents causes troublesome symptoms and/or complications.1 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.2 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 
DATABANK INFO 
NEEDED: 
      No 
      Yes 
    Specify 
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    _________ 

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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.2 
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.3 Proton pump inhibitors also have unmet issues 
needing improvement. PPIs usually takes 5 days for their maximal effect4-5. Because of their slow onset 
of action, a significant number of patients are not sufficiently relieved after the first dose of PPI.6-7 
Approximately half of patients still have symptoms after 3 days of treatment7. PPIs are influenced by the 
cytochrome P450 (CYP) 2C19 polymorphism, with rapid metabolizers having the lowest intragastric pH 
compared with slow metabolizers.8-9 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.10-12 
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.13 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.14-15 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.16-17  

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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.13 Studies are 
ongoing in Japan to assess the long term safety and efficacy of vonoprazan.13 
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.18 
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. 
 
2.1 RESEARCH QUESTION 
 
Is vonoprazan more effective than omeprazole as empiric therapy in relieving symptoms of 
patients with gastroesophageal reflux disease (GERD) without alarm symptoms? 
 
3. OBJECTIVES 
The objectives of this study are the following: 
1. To compare the effectiveness of vonoprazan against omeprazole in relieving symptoms of GERD 
using the Frequency Scale of Symptoms of GERD (FSSG) questionnaire at Days 3, 7 and 14 
days of treatment, specifically: 
a. Proportion of complete responders/partial responders/nonresponders at each time point 
between vonoprazan group and omeprazole group 
b. Difference in the percent change in the symptom score from baseline using the FSSG 
questionnaire at each time point within both groups 

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c. Difference in the percent change in the symptom score from baseline using the FSSG 
questionnaire at each time point between vonoprazan group and omeprazole group 
2. To assess the safety of vonoprazan compared with omeprazole in patients with clinically 
diagnosed GERD 
 
4. METHODOLOGY 
 
4.1 Study Design  
 
 This is a pragmatic, randomized, single blind controlled trial comparing effectiveness of 
vonoprazan against omeprazole in relieving symptoms of GERD. Patients clinically diagnosed with 
GERD will be recruited from the clinics of participating gastroenterologists. Symptoms will be assessed 
using the locally validated Frequency Scale of Symptoms of GERD (FSSG) questionnaire by Lontok, 
et.al. Adverse events will be recorded via symptom diary given to patients. 
 
Figure 1. Flowchart of Study Methods 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adult patients with clinically diagnosed 
GERD without alarm features from clinics 
of participating gastroenterologists 
Written consent 
Randomization c/o research assistant using 
www.randomizer.org 
Vonoprazan 20mg 
once daily for 14 days 
Omeprazole 40mg 
once daily for 14 days 
Re-evaluation 
FSSG Questionnaire at Days 3, 7, 14 days 
Baseline FSSG Questionnaire 
Statistical Analysis 

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4.2 Participants 
Inclusion criteria  
i. 
All Adult patients with clinically diagnosed with Gastroesophageal Reflux Disease 
(GERD) without alarm features (heartburn and acid regurgitation) 
ii. 
Age more than 18 years at the time of written consent 
iii. 
Those who provide written consent with their own free will 
iv. 
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 
i. 
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) 
ii. 
Patients with atypical GERD symptoms (cough, laryngitis, chest pain, etc.) 
iii. 
Patients already taking proton pump inhibitors for the past 2 weeks 
iv. 
Patients who scored less than 8 on the FSSG questionnaire 
v. 
Patients who have undergone gastroesophageal surgery 
vi. 
Patients who are poorly compliant to medications 
vii. 
Allergic to PPI or vonoprazan 
viii. 
With serious comorbidities, such as but not limited to: heart failure, renal failure, 
malignancy or hepatic failure 
ix. 
Pregnant, breastfeeding or possibly pregnant 
x. 
Patients that would not provide consent 
xi. 
Patients who are unable to complete the FSSG Questionnaire independently 
xii. 
Patients who are unable to follow up at designated periods 
xiii. 
Patients taking rilpivirine or atazanavir. 
xiv. 
Patients with elevated baseline liver function tests (more than twice the upper limit of 
normal) 
4.3 Study Setting 
 
St. Luke’s Medical Center – Quezon City, a private tertiary hospital 
 
 
 

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4.4 Sampling and Sample size 
 
Sample size was calculated based on the comparison of patients with erosive esophagitis Grade 
C/D given a P-CAB or PPI, assuming that success rate among patients given PPI is 82.6% and among 
those given PCAB is 96% (Ashida, 2015), with an alpha error of 5%, power of 80% and one tailed 
alternative hypothesis. Sample size required is 89 per group or 178 for 2 groups; allowing for 25% 
dropout rate, final sample size is 224 patients. 
 
4.5 Study duration: 1 year and 6 months 
 
4.6 Outcome:   
Primary outcome: Proportion of asymptomatic patients. Asymptomatic patients is defined as a patient 
being free of symptoms of heartburn or acid regurgitation according to FSSG questionnaire (score <8) 
on day 3, 7, and 14 of therapy. 
 
Secondary outcome:  
a. Proportion of partial responders, nonresponders at each time point: day 3, 7, and 14 of 
therapy 
b. Difference in the percent change in the symptom score from baseline using the FSSG 
questionnaire at each time point within Vonoprazan and omeprazole group 
c. Difference in the percent change in the symptom score from baseline using the FSSG 
questionnaire at each time point between vonoprazan group and omeprazole group 
d. Safety and frequency of adverse effects experienced by patients (nasopharyngitis, 
diarrhea, constipation, upper respiratory tract infection, gastroenteritis, eczema/allergy, 
hypergastrinemia) 
 
 
4.7 Study Procedures 
4.7.1 Recruitment 
 
Patients will be recruited from private and social service outpatient clinics of gastroenterologists 
of St. Luke’s Medical Center - Quezon City. Letters of invitation will be distributed to all consultant 
gastroenterologists containing the inclusion and exclusion criteria of the participants. The research 
protocol will also be presented at the research update conference of the Institute of Digestive and Liver 
Diseases.  
 

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4.7.2 Randomization 
Patients who will give written consent will be randomized to receive either vonoprazan or 
omeprazole for the treatment of GERD for 14 days. Randomization will be done using an online research 
randomizer website: www.randomizer.org. The research assistant will handle the randomization, 224 
random number assignment will be generated using the website. The research assistant will list the 
participants in a database containing the study drug assignment for which only the research assistant 
has access.  
4.7.3 Baseline Characteristics 
Baseline characteristics will be acquired from the participants, specifically: age, sex, body mass 
index [BMI], smoking [never smoked, current smoker, previous smoker], alcohol consumption [daily, 2-
3 days a week, 2-3 days a month, never], caffeine consumption, comorbids [hypertension, diabetes, 
others] and history of GERD treatment [antacids, H2 blockers, proton pump inhibitor]. After 
randomization, patients on each arm will be asked to answer the locally validated FSSG questionnaire 
in English or Tagalog form as baseline evaluation. General data specifically the name, address, email, 
phone numbers, and referring physician will also be acquired. 
4.7.4 Participation 
Once the participant is deemed eligible for the study, participants will be guided to the laboratory 
for blood extraction [CBC, liver function test, GGT, LDH, Creatinine]. Once the baseline laboratory 
parameters are acceptable, the research assistant will then give the participants a prescription 
containing a code to the assigned study drug, which will be dispensed by the hospital pharmacy. The 
research assistant may guide the study participants to the pharmacy department to procure the study 
medication. Patient will then continue to take their medication and asked to follow up and reevaluate 
their symptoms on day 3, 7 and 14 of treatment using again the FSSG questionnaire, which will be 
facilitated by the research assistant or the lead investigators. On day 14, after answering the FSSG 
questionnaire, patients will be directed to the laboratory for repeat blood examination [CBC, liver function 
test, GGT, LDH, Creatinine]. 
 

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4.7.5 Blinding 
Due to difficulties in logistics, the study will follow single blinding procedures. Only the principal 
investigators will be blinded to the study group assignment; the research assistant and the participants 
will be unblinded. We recognize a potential bias to the study results may occur since study participants 
may compare what drugs they are taking; but since both drugs have therapeutic value, the bias as a 
result of nonblinding of study participants will be minimal. Coordination with the pharmacy will be done 
regarding coded prescription for the assigned study drug. The pharmacy will dispense labeled tablets in 
their original packaging from the manufacturer. 
Table 1 – Study procedure/Flow 
Day 0 
 Recruitment from Clinics 
 Briefing and orientation on the trial c/o primary investigators (PI) 
 Signing of informed consent form c/o primary investigators (PI) 
 Baseline characteristics: age, sex, BMI, smoking [never smoked, current 
smoker, previous smoker], alcohol consumption [daily, 2-3 days a week, 
2-3 days a month, never], caffeine consumption, comorbids 
[hypertension, diabetes, others] and history of GERD treatment 
[antacids, H2 blockers, proton pump inhibitor]. General data specifically 
the name, address, email, phone numbers, and referring physician will 
also be acquired. – c/o PI or research assistant (RA) 
 Answering of FSSG questionnaire  
 Blood extraction (CBC, LFT, GGT, LDH, Creatinine) 
Day 0/1 
 Interpretation of laboratory results 
 Screening using Inclusion and Exclusion Criteria 
 Randomization c/o research assistant (RA) 
 Issuance of Coded Prescription – c/o RA 
 Proceed to Pharmacy to acquire medication 
 Issuance of Travel allowance and notebook (symptom diary) for the next 
visit – P100 
Day 1/2 
 First intake of study medication 
Day 4 
 Answer FSSG Questionnaire 
 Review of symptom diary/Interview for any adverse effects 
 Issuance of Travel allowance 
Day 8 
 Answer FSSG Questionnaire 
 Review of symptom diary/Interview for any adverse effects 
 Issuance of Travel allowance 
Day 15 
 Answer FSSG Questionnaire 
 Review of symptom diary/Interview for any adverse effects 
 Last dose of study medication in the morning 
 Blood extraction (CBC, LFT, GGT, LDH, Creatinine) 
Day 43 (6 weeks) 
 Follow up phone call for any adverse effects/events 
 
 

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4.7.6 Adverse Events Reporting 
 
Screening for adverse events will be sought at every visit for reevaluation and noted at an 
electronic excel file. All serious adverse events (SAE) from the start to the completion of the trial until 6 
weeks after taking the medications will be collected. All SAEs will be followed up until the event is 
confirmed (death, recovery, or loss to follow up). 
 
4.7.7 Study Medication 
This study will compare and use 2 study medications, both are branded medications and approved by 
the FDA. Participants will be instructed to take both tablets 30 minutes before breakfast. 
Table 2 – Medications to be used in the study 
Drug 
Dose 
Brand 
Manufacturer 
Distributor 
Omeprazole 
40mg capsule 
Omepron 
Ajanta 
Pharmaceutical 
United 
Laboratories, Inc. 
Vonoprazan 
20mg tablet 
Vocinti 
Takeda 
Pharmaceutical 
Takeda 
Healthcare 
 
Table 3 – Adverse Effects of medications to be used in the study 
Drug 
Adverse Effects (Frequency) 
Omeprazole 
 
Headache (7%) 
 
Abdominal pain (5%) 
 
Diarrhea (4%) 
 
Nausea (4%) 
 
Vomiting (3%) 
 
Flatulence (3%) 
 
Dizziness (2%) 
 
Upper respiratory tract infection (2%) 
 
Acid Regurgitation (2%) 
 
Constipation (2%) 
 
Rash (2%) 
 
Cough (1%) 
Vonoprazan 
Frequency 0.1%- less than 5% 
 
Constipation 
 
Diarrhea 
 
Feeling of enlarged abdomen 
 
Nausea 
 
Rash 
 
Increased AST/ALT/ALP/LDH/GGT 
 
Edema 
 
Eosinophilia 
 

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4.7.8 Early withdrawal and Lost to follow up 
 
Withdrawal or premature termination from the trial may be due, but not limited to: patient’s 
decision to withdraw, adverse events, failure to follow protocol, follow up visits, or intake of study 
medications, or the investigator’s decision to safeguard patient’s safety. The reason for premature 
termination/withdrawal from the trial will be noted and recorded. Participants who will withdraw 
prematurely will be instructed to return to their gastroenterologists for appropriate treatment of their 
GERD symptoms. The attending gastroenterologist will also be informed of the patient’s premature 
termination. 
 
In cases of participants unable to follow up strictly on designated periods, a time allowance limit 
of two weeks from last follow up date will be enforced; otherwise, the participant will be declared lost to 
follow up and will be dropped from the study. To ensure adequate follow up, all participants will be 
reminded to follow up with all possible means: phone call, short messaging service and electronic media 
(eg. Viber and Facebook Messenger). 
 
Vonoprazan and Omeprazole are generally well tolerated and adverse effects are usually mild 
and well tolerated. Adverse effects are as summarized above. Patients experiencing side effects will be 
given appropriate management as follows: headache will be prescribed with paracetamol 500mg tablet 
every 6 hours as needed for headache; cough and colds will be prescribed with either acetylcysteine 
600mg sachet twice a day for 5 days or a combination tablet of chlorphenamine + paracetamol + 
phenylpropanolamine every 6 hours for 7 days; constipation will be prescribed with polyethylene glycol 
17g/sachet as needed; diarrhea will be managed expectantly, patients will be advised to increase oral 
fluid intake; rashes or allergies, levocetirizine 5mg/tablet for 5 days. These medications are included in 
the budget and will be provided to participants for free. Other medications will be prescribed as needed 
for unexpected minor adverse events.  
Patients who have elevations of more than twice the upper limit of normal on the liver function 
test (ALT, AST, TPAG, Total bilirubin, direct bilirubin, indirect bilirubin, LDH, GGT) will be asked to stop 
taking their assigned medication and asked to repeat liver function test after two weeks to document 
resolution of the increase in liver function test. In cases where the liver function test still doesn’t improve 
after two weeks, they will be referred to a hepatologist. All subsequent, professional fee, workup and 
medications recommended by the hepatologist will be shouldered by the study and provided to the 
participant for free. 
 
 
4.8 Data Management and Analysis: 
 
All data collected will be plotted in an electronic excel file and secured with a password known 
to proponents only.  

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The data gathered will be described using frequency and percentage for categorical variables 
and mean +/- SD for continuous variables.  
 
4.9 Statistical Analysis 
 
For the primary outcome on the proportion of complete responders, comparison of the 
effectiveness between PCAB and PPI will be analyzed using the chi-squared test. Risk ratio in the 95% 
confidence interval will also be calculated. Difference in percent change of FSSG score within groups 
will be computed using the paired T test. 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; repeat measures ANOVA will also be computed to compare 
percent change between different time points (baseline, day 3, 7, and 14). Comparison of adverse 
outcome for the 2 drugs will also be analyzed using chi-squared test.  Level of significance will be set at 
alpha 0.05. 
4.10 Operational Definitions 
1. Complete Responder/Asymptomatic patients - patients free of symptoms of heartburn or 
acid regurgitation according to FSSG questionnaire on day 3, 7, and 14 of therapy; patients 
who scored <8 for symptoms on the FSSG questionnaire 
2. Partial Responders/GERD Symptom Relief – 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 
3. Nonresponders – Patients who reported no significant improvement in symptoms with 
treatment; patients with less than 50% reduction from the baseline FSSG score 
4. Percent change in the symptom score – [baseline FSSG score – re-evaluated FSSG score] 
divided by the baseline FSSG score 
4.11 Ethical Considerations 
 
The study will abide by the Principles of the Declaration of Helsinki (2013) and will be conducted 
along the Guidelines of the International Conference on Harmonization – Good Clinical Practice (ICH-

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GCP). The Clinical Protocol and all relevant documents shall be reviewed and approved by the SLMC 
Institutional Ethics and Review Committee. Patient confidentiality shall be respected by ensuring 
anonymity of patient records. Each patient document is CODED and will not contain any identifying 
information in order to ensure confidentiality. All study data shall be recorded and investigators are 
responsible for the integrity of the data i.e. accuracy, completeness, legibility, originality, timeliness and 
consistency. The manner of disseminating and communicating the study results shall guarantee the 
protection of the confidentiality of patient’s data. 
 
Study documents will be kept for 5 years after publication. Documents will be stored at the 
Institute of Digestive and Liver Disease – St. Luke’s Medical Center, Quezon City. After five years, the 
documents will be shredded and burned before disposal. 
 
No life-threatening risks are foreseen to happen to the participants of the study. The side effects 
of both drugs are rare, mild and transient as listed above. There is the inconvenience of having to come 
back on days 3, 7, and 14 for reevaluation. The study will provide P100 travel allowance per visit to 
participants to cover for travel expenses. 
 
Medications for treatment of acid reflux and baseline lab exams will be provided to patients for 
free. Medications to treat the side effects will also be provided for free to patients as well. Results 
generated from this study will contribute to the advancement for the treatment of gastroesophageal 
reflux disease (GERD). 
 
In cases of any adverse events or medical injury as a result of participating in this trial, 
participants will call/contact the primary investigators, Dr Nicodemus Ong (Phone 09176791018) and Dr 
Sherrie de Ocampo (Phone 09175607155) for appropriate instructions and actions. The budget for this 
study will include medications to treat common side effects of the drug, with provision for admission for 
any serious allergic reactions. The medications to treat the common side effect of the drug will be 
provided to participants free of charge. 
 
 
 
 
 

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5. COLLABORATORS/SPONSORSHIP 
 
Researchers plan to ask for sponsorship from the research fund of St. Luke’s Medical Center Quezon 
City, Research and Biotechnology Department. Research proponents does not plan to ask for assistance 
from any pharmaceutical company to minimize conflict of interest. 
 
 
6. RESULTS 
 
A. Table for Collection of Raw Data 
 
Patient 
Initials 
Patient 
ID 
Age 
Gender 
FSSG 
Score 
Baseline 
– Day 0 
FSSG 
Score 
Day 3 
FSSG 
Score 
Day 7 
FSSG 
Score 
Day 14 
Adverse 
Events 
Reported 
Asymptomatic/ 
Partial 
responder/ 
Nonresponder 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 1. Table for Collection of Raw Data 
 
 
 
 
B. Dummy Table for the Primary Outcome  
 
Table 2. Proportion of asymptomatic patients 
 
 
C. Dummy Table for the Secondary Outcomes 
Table 3. Proportion of Partial Responders and Nonresponders 
Proportion of  Complete Responders/Asymptomatic Patients 
Chi-squared Test 
 
Vonoprazan 
Omeprazole 
Day 3 
 
 
 
Day 7 
 
 
 
Day 14 
 
 
 
Proportion of  Partial Responders/GERD Symptom Relief 
Chi-squared Test 
 
Vonoprazan 
Omeprazole 
Day 3 
 
 
 
Day 7 
 
 
 
Day 14 
 
 
 
 
 
 
 
Proportion of Nonresponders 
Chi-squared Test 
 
Vonoprazan 
Omeprazole 
Day 3 
 
 
 
Day 7 
 
 
 
Day 14 
 
 
 

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Table 4. Mean FSSG Score within Vonoprazan and Omeprazole Groups 
 
 
 
 
Adverse Events 
Vonoprazan 
(number of patients) 
Omeprazole 
(number of patients) 
F test 
Nasopharyngitis 
 
 
 
Diarrhea 
 
 
 
Constipation 
 
 
 
Upper respiratory infection 
 
 
 
Gastroenteritis 
 
 
 
Mean FSSG score Vonoprazan Group – each will be compared to 
baseline 
 
Mean FSSG Score 
Paired T Test 
Baseline 
 
 
Day 3 
 
 
Day 7 
 
 
Day 14 
 
 
[Compare 
between 
different time 
points] 
Repeat Measures of 
ANOVA 
[Result of Repeat Measures 
of ANOVA] 
 
Mean FSSG score Omeprazole Group – each will be compared to 
baseline 
 
Mean FSSG Score 
Paired T Test 
Baseline 
 
 
Day 3 
 
 
Day 7 
 
 
Day 14 
 
 
[Compare 
between 
different time 
points] 
Repeat Measures of 
ANOVA 
[Result of Repeat Measures 
of ANOVA] 

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Eczema/Allergy/Eosinophilia  
 
 
Increased SGPT 
 
 
 
Increased SGOT 
 
 
 
Increased ALP 
 
 
 
Increased Bilirubin 
 
 
 
Increased GGT 
 
 
 
Increased LDH 
 
 
 
Table 5. Adverse events 
 
 
 
 
 
7. REFERENCES 
 
1. Vakil, N., van Zanten, S., et. Al. (2006) The Montreal Definition and Classification of 
Gastroesophageal Reflux Disease: A Global Evidence-Based Consensus, American Journal of 
Gastroenterology. 101, pp 1900-1920 
2. Sollano, J., Romano, R., et. Al. (2015) Clinical Practice Guidelines on the Diagnosis and 
Treatment of Gastroesophageal Reflux Disease (GERD). Philippine Journal of Internal 
Medicine. 53 (3), pp 1-17 
3. Lontok, M., Romano, R., Sollano, J. (2013) Symptoms Response to PPI therapy of GERD 
patients managed by primary care physicians. (Abstract). Journal of Gastroenterology and 
Hepatology. 28; 23-693 
4. Cederberg, C., Lind, T., Rohss, K., Olbe, L. (1992) Comparison of once daily intravenous and 
oral omeprazole on pentagastrin-stimulated acid secretion in duodenal ulcer patients. 
Digestion. 53:171-178 
5. Dammann, HG., Burkhardt, F.,(1999) Pantoprazole vs omeprazole: influence on meal 
stimulated gastric acid secretion. European Journal of Gastroenterology and Hepatology. 11: 
1277-1282 
6. Bytzer, P., Morocutti, A., Kennerly, P., Ravic, M., et.al. (2006) Effect of rabeprazole and 
omeprazole on the onset of gastroesophageal reflux disease symptom relief during the first 
seven days of treatment. Scandanavian Journal of Gastroenterology. 41: 1132-1140. 
7. Peura, DA., Riff, DS., Snoddy, AM., Fennerty, MB., (2009) Clinical Trial: Lansoprazole 15 or 30 
mg once daily vs placebo for treatment of frequent nighttime heartburn in self-treating subjects. 
Alimentary Pharmacology and Therapeutics. 30:459-468. 
8. Chong, E., Ensom, MH., (2003) Pharmacogenetics of proton pump inhibitors: a systematic 
review. Pharmacotherapy. 23: 460-471. 
9. Furuta, T., Shirai, N., Sugimoto, M, et.al. (2005) Influence of CYP2C19 pharmacogenetic 
polymorphism on proton pump inhibitor based therapies. Drug Metabolism and 
Pharmacokinetics. 20: 153-167. 
10. Katz, PO, Castell, DO, et al. (2004) Intragastric acid suppression and pharmacokinetics of 
twice daily esomeprazole: a randomized, three way crossover study. Alimentary Pharmacology 
and Therapeutics. 20:399-406. 
11. Johnson, DA, Katz, PO, (2008) Nocturnal gastroesophageal reflux disease: issues, implications 
and management strategies. Review in Gastrointestinal Disorders. 8: 98-108 
12. Fass, R., Chey, WD., Zakko, SF., (2009) Clinical Trial: the effects of the proton pump inhibitor 
dexlansoprazole MR on daytime and nighttime heartburn in patients with nonerosive reflux 
disease. 29: 1261-1272 
13. Oshima, T., Miwa, H. (2018) Potent Potassium-Competitive Acid Blockers: A New Era for the 
Treatment of Acid related Diseases. Journal of Neurogastroenterology and Motility. 24(3): 334-
344 

Protocol Version 10 dated 15 December 2019 
 
16
14. Ashida, K., Sakrai, Y., et. Al. (2016) Randomized clinical trial: vonoprazan, a novel potassium 
competitive acid blocker vs lansoprazole for healing of erosive esophagitis. Alimentary 
Pharmacology and Therapeutics. 43:240-51 
15. Iwakiri, K, Sakurai, Y., et al. (2017) A randomized, double blind study to evaluate the acid 
inhibitory effect of vonoprazan (20 and 40mg) in patients with proton pump inhibitor resistant 
erosive esophagitis. Therapeutics Advances in Gastroenterology. 10(6): 439-451 
16. Shinozaki, S., Osawa, H., et al. (2017) Vonoprazan 10 mg daily is effective for the treatment of 
patients with proton pump inhibitor resistant gastroesophageal reflux disease. Biomedical 
Reports. 7: 231-235 
17. Kinoshita, Y., Sakurai, Y., Shiino, M., et al. (2016) 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. Current Therapeutic 
Research. 81-82C:1-7 
18. Kusano, M., Yasuyuki, S., Sugimoto, S., et al. (2004) Development and Evaluation of FSSG: 
Frequency Scale for the Symptoms of GERD. Journal of Gastroenterology. 39: 888-891 
19. Mori, H.; Suzuki, H. (2019) Role of Acid Suppression in Acid-Related Diseases: Proton Pump 
Inhibitor and Potassium Competitive Acid Blocker. Journal of Neurogastroenterology and 
Motility. 25(1): 6-14 
 
 
 
 
 

Protocol Version 10 dated 15 December 2019 
 
12
 
APPENDIX A 
Frequency Scale for the Symptoms of GERD (FSSG) questionnaire 
 
 
Date 
 
Patient ID 
 
Age 
 
Gender 
 
 
Question 
Never 
(0%) 
Occasion
ally (30%) 
Somet
imes 
(50%) 
Often 
(70%) 
Always 
(100%) 
1 
Do you get heartburn? 
0 
1 
2 
3 
4 
2 
Does your stomach ever get bloated? 
0 
1 
2 
3 
4 
3 
Does your stomach ever feel heavy after meals? 
0 
1 
2 
3 
4 
4 
Do you sometimes subconsciously rub your chest with your hand? 
0 
1 
2 
3 
4 
5 
Do you ever feel sick after meals? 
0 
1 
2 
3 
4 
6 
Do you get heartburn after meals? 
0 
1 
2 
3 
4 
7 
Do you have an unusual (eg burning) sensation in your throat? 
0 
1 
2 
3 
4 
8 
Do you feel full while eating meals? 
0 
1 
2 
3 
4 
9 
Do some things get stuck when you swallow? 
0 
1 
2 
3 
4 
10 Do you get bitter liquid (acid) coming up into your throat? 
0 
1 
2 
3 
4 
11 Do you burp a lot? 
0 
1 
2 
3 
4 
12 Do you get heartburn if you bend over? 
0 
1 
2 
3 
4 
 
Total 
 
 
 
 
 
 
Total Score 
 
 
 
 
 
 
 
 

13 
Protocol Version 10 dated 15 December 2019 
 
APPENDIX B 
Frequency Scale for the Symptoms of GERD (FSSG) questionnaire 
Locally Validated 
 
 
Petsa 
 
Patient ID 
 
Edad 
 
Kasariaan 
 
 
Tanong 
Hindi 
(0%) 
Sobrang 
Minsan 
(30%) 
Minsan 
(50%) 
Madalas 
(70%) 
Lagi 
(100%) 
1 
Kinakabagan ka ba? 
0 
1 
2 
3 
4 
2 
Nakakaramdam ka ba ng sakit, hapdi o init sa sikmura na 
gumuguhit  paakyat hanggang dibdib? (Nakakaramdam ka ba ng 
“heartburn?” 
0 
1 
2 
3 
4 
3 
Humahapdi/sumasakit baa ng iyong sikmura kahit hindi pa 
nakakain? 
0 
1 
2 
3 
4 
4 
Nakakranas ka ba ng “Heartburn” kapag nakakain ka ng mga 
piling pagkain? (Nakakaranas k aba ng sakit, hapdi, o init sa 
sikmura na gumuguhit paakyat hanggang dibdib kapag nakakain 
ng mga piling pakain?) 
0 
1 
2 
3 
4 
5 
Sumasama ba ng iyong pakiramdam kapag naparami ang 
nakain? 
0 
1 
2 
3 
4 
6 
Nakakaramdam ka ba ng pamumuno ng sikmura kaagad 
pagkatapos kumain? 
0 
1 
2 
3 
4 
7 
Sumasama baa ng iyong pakiramdam kapag hinihigpitan ang 
iyong tiyan? 
0 
1 
2 
3 
4 
8 
May nalasahan ka bang maasim na umaakyat hanggang bibig? 
0 
1 
2 
3 
4 
9 
Mayroon bang maiinit na pakiramdam sa sikmura na umaakyat 
hanggang dibdib? 
0 
1 
2 
3 
4 
10 
Mabigat ba ang iyong sikmura pagkatapos kumain? 
0 
1 
2 
3 
4 
11 
Sumasama baa ng iyong pakiramdam pagkatapos kumain ng 
mamantika/matatabang pagkain? 
0 
1 
2 
3 
4 
12 
Madalas ka bang dumighay? 
0 
1 
2 
3 
4 
 
Total 
 
 
 
 
 
 
Total Score 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

14 
Protocol Version 10 dated 15 December 2019 
 
 
APPENDIX C 
Product Insert of Omeprazole 40mg capsule [Omepron] and Vonoprazan 20mg tablet [Vocinti] 
 
 
 

13 
Protocol Version 10 dated 15 December 2019 
 
 
B. Proposed Budget 
 
See attached Budget Proposal 
 
 
 
 
C. GANTT CHART 
 
ACTIVITY 
Sept to Nov 
2018 
Dec 2018 to 
March 2020 
Feb to March 
2020 
March to 
April 2020 
Research/Writing 
of Protocol 
  
  
 
  
Presentation 
to 
IRB 
  
  
 
  
Data Gathering 
 
 
 
 
Data 
Interpretation 
  
 
 
  
Writing of Final 
Paper 
  
 
 
  
Presentation 
of 
Final Paper 
  
  
 
  
Editing