When setting up the study, the target number of enrolled patients was set at 150, but in reality, the planned number of patients was unable to be collected within the study period; thus, totaling 99 patients were enrolled. Of these, 93 subjects for whom FSSG scores on Day 1 were available were included in the analyses.
Patient background: Table 1 summarizes the summary statistics (mean ± SD) on Day 1 for the background factors and treatment factors that may affect eGERD treatment and shows the values for the entire patient population and for the respective PPI and VPZ groups, though the primary endpoint targeted the entire population only. Of the included 93 patients, male and female were respectively 55 (59.1%) and 38 (40.9%), without significant difference. Seventy subjects (75.3% of the total) were over 60 years of age. The drugs administered were either PPIs (esomeprazole: 27 cases, omeprazole: 1 case, rabeprazole: 15 cases, lansoprazole: 4 cases) or VPZ.
Although it was not initially set as an endpoint, since almost the same number of patients (N=45-47) were included in each PPI and VPZ group, we deviated from protocol to conduct inter-group comparison, and in Table 1 gives the data for the respective groups. The results show that there were statistically significant inter-group differences (p<0.05) for sex, BMI, blood gastrin levels, blood pepsinogen I, II levels, I/II ratios, and LA classification A/B, but no inter-group differences in other parameters.
Symptom relapse after drug withdrawal, non-relapse factors, and change in blood gastrin level: Mean±SD of summary statistics at Week 4 for the same items as in Table 1 is shown for entire population and the patients stratified by FSSG < 8 (non-relapse) and FSSG≥ 8 (relapse) (Table 2).
Although symptoms of 92 patients could be assessed just before and after the withdrawal, since there were some subjects missing some data for the items on Day 1 or Week 4, the evaluation of variations could be performed in 91 cases. Of the 91 patients, 66 (72.5%) had FSSG <8 after withdrawal.
There was no statistically significant difference (p<0.05) between the patients with FSSG< 8 and FSSG≥ 8 in any of the items examined, and there was no association of symptom relapse with any of the factors.
Table 3 shows the respective blood gastrin levels and variations from Day 1 to Week 4 for entire population and each group. The amount of variation was significantly lower at Week 4. Since there was already a significant inter-group difference on Day 1, we performed a covariance analysis using the Day 1 values as covariates; the inter-group difference was statistically insignificant at p=0.808 (Table 4).
Symptom transition after drug suspension: Table 5 shows the FSSG total scores at Day 1 and each Week for entire population and the patients in the two groups. The total scores at each Week were higher than those on Day 1 with statistical significance (p<0.001) in the two dose groups and entire population. Comparison of the two groups for the variations in FSSG total scores at each time point (unpaired t-test) demonstrates that the VPZ group was higher than the PPI group, though without statistical significance (Fig. 1). The results of the subscores by acid reflux-related symptom and motor deficiency symptom are shown in Tables 6 and 7, respectively. The comparison of the amount of variation in the FSSG subscores at each time point shows an increasing trend over time without significant difference, and the comparison of the two groups (unpaired t-test) shows no significant difference. However, all the subscores were higher in the VPZ group than those in the PPI group at each time point (Figs 2 and 3).
Next, we examined the GSRS total scores/subscores and the HADS scores; between Day 1 and each time point, there was no significant difference in the amount of variations in the HADS scores but the difference in the GSRS total score was significant at p<0.001. There were also significant differences in the subscales of acid reflux and abdominal pain. Indigestion, diarrhea, and constipation, however, show no significant difference (See Table 1 in Supplementary file).
The percentage of subjects with FSSG total score of ≥8 in the two groups and entire population was calculated using the number of subjects on Day 1 as the denominator (Fig. 4). To assess whether the distribution of FSSG total score (<8/≥8) at each time point differed among the ASIDs, we compared it by Fisher's exact probability test. As a result, no statistically significant difference was obtained at any time points. The number of subjects in the VPZ group with FSSG total score of ≥8, however, remained around 30% except for 39.1% at Week 3. In the PPI group, the number of subjects with FSSG total score of ≥8 showed an upward tendency over time from approximately 15% to 21% except for 27.7% at Week 4.
A single regression analysis was performed with the amount of variations in FSSG total scores at Week 4 as the objective variable and the background factors of continuous volume (age, BMI, blood gastrin levels, and pepsinogen I/II ratios at enrollment) and questionnaire results at the enrollment (total scores of FSSG, GSRS, and HADS) as explanatory variables. No statistically significant correlations were observed for any of the factors, and for the FSSG subscores. Single regression analysis of the variations in GSRS subscores at Week 4 shows weak correlations with BMI of 0.2562 for the acid reflux subscore, Day 1 blood gastrin level of 0.2081 for abdominal pain, and age of 0.2874 for the constipation score (See Table 2 of Supplementary file).