Brief Methodology:
It is an Open Label, Randomized, Comparative, Multicenter,
Prospective, Clinical Study to evaluate efficacy and safety of Ayucid Capsules
and Omeprazole (20 mg) in Patients Suffering from Chronic symptomatic
Gastro-esophageal Reflux Disease (GERD). The study will be conducted in 60
patients at three sites in India. Subjects from group A will be advised to take
Ayucid Capsules in a dose of 2 capsules twice daily, orally before meals with
water for 28 days. Subjects from group B will be advised to take Capsule
Omeprazole 20 mg once daily before lunch with water for 28 days. Primary
outcome of the study would be to assess complete resolution of heartburn in two groups on Day -3, Day 0, Day
7, Day 14, Day 21 and Day 28. Secondary outcomes of the study would be to
assess effect of Ayucid Capsule and Omeprazole on other symptoms of GERD, i.e.,
acid regurgitation, dysphagia, epigastric pain, and nausea, to assess
requirement of rescue medication (antacid) use each day through diary card in
two study groups, to assess quality of life (QOL) on GERD - Health Related QOL
Questionnaire (GERD HRQL) in the two study groups, to assess other digestion
related symptoms in the two study groups, to assess safety based on clinical
adverse events and laboratory test results in the two study groups and to
assess overall improvement by subject and investigator at the end of study
treatment. Results:
A total of 91 subjects were screened in
the study. There were 16 screen failures as they did not meet inclusion /
exclusion criteria. Of these subjects, 75 subjects were randomized into two
groups. There were 12 dropouts in the study, which were due to reasons other
than occurrence of adverse events (did not provide follow up). A total of 63
subjects were considered as completers or efficacy evaluable cases, 33 subjects
were in Ayucid Group and 30 subjects were in Omeprazole 20 mg Group. All the subjects who took even a single dose
of any study drug were considered for safety evaluation.
Of the 33 subjects in Ayucid group,
there were 15 males and 18 females. Out of the 30 subjects in Omeprazole group,
there were 11 males and 19 females. The average age of subjects in the Ayucid
Group was 45.70 ±9.41 years while in the Omeprazole Group it was 39.73 ±9.02
years. There was no significant difference in the age of subjects in the two
study groups.
In the Ayucid group it was observed
that there was 1 subject of Pittaja and Vata-Kaphaja Prakruti each, 2 subjects
of Kapha-Pittaja Prakruti, 7 subjects of Pitta-Kaphaja Prakruti, 8 subjects of
Pitta Vataja Prakruti and 14 subjects of Vata- Pittaja Prakruti. In Omeprazole
group it was observed that there were 4 subjects of Vata-Kaphaja Prakruti, 2
subjects of Kapha-Pittaja Prakruti, 5 subjects of Pitta-Kaphaja Prakruti, 7
subjects of Pitta Vataja Prakruti and 12 subjects of Vata- Pittaja Prakruti.
At the end of
28 days of study subjects were evaluated for complete resolution of their
occurrence of heart burn. There was complete resolution of heart burn in 14
subjects (42.42%) in Ayucid group while the same was observed in 17 subjects
(56.66%) in Omeprazole group. It was observed that there was no significant
difference between the two groups i.e. the effect in both the groups was equal.
In Ayucid group, there were 6 (18.18%) subjects who
experienced complete absence of heart burn on day 7. On day 14 and 21, there
were 5 (15.15%) and 11 (33.33%) subjects who experienced complete resolution of
the heart burn respectively. In Omeprazole group, 9 (30%), 10 (33.33%) and 10
(33.33%) subjects experienced complete resolution of heart burn on day 7, day
14 and day 21 respectively.
It was
observed that there was a significant reduction in the severity of heart burn
from baseline to each follow up visits in both the groups starting from day 7.
The baseline score of severity of heart burn in Ayucid group was 2.33 ±0.54
which reduced significantly to 1.25 ±0.88 on day 7. The mean score of severity of
heart burn reduced further to 1.17 ±0.71 and 0.79 ±0.73 respectively on day 7
and 14. At the end of the study the mean score of severity of heart burn was
0.58 ±0.50. In Omeprazole group, the mean score of severity of heart burn was 2.17
±0.59 at baseline which reduced significantly to 0.92 ±0.86 at the end of 7
days. The mean score of severity of heart burn further reduced to 0.72 ±0.68, 0.52
±0.51 and 0.43 ±0.50 on day 14, 21 and 28 respectively. There was no
significant difference between the two groups at all the follow up visits i.e.
between groups effects were equal.
At baseline visit, the mean score for
severity of acid regurgitation in Ayucid group was 1.76 ±0.87, which reduced significantly to 1.03 ±0.86 on day 7. The mean score for severity of acid regurgitation further
reduced significantly to 0.76 ±0.74
on day 14, 0.62 ±0.56 on day 21
and 0.39 ±0.50 on day 28. The
mean score of severity of acid regurgitation in Omeprazole group was 1.80 ±0.80 at baseline, which reduced
significantly to 0.80 ±0.76 on
day 7. The mean score for severity of acid regurgitation reduced significantly to
0.56 ±0.58 on day 14, 0.48 ±0.51 on day 21 and 0.23 ±0.43 on day 28. There was no
significant difference between the two groups at baseline and on each follow up
visits i.e. between groups effects were
equal.
The mean score for severity of
dysphagia in Ayucid group was 0.97 ±1.02
on baseline visit, which reduced to 0.66 ±0.90 at the end of 7 days. The mean score for severity of dysphagia further
reduced to 0.34 ±0.67, 0.24 ±0.44 and 0.09 ±0.29 on day 14, day 21 and day 28 respectively. These reductions
were found to be significant at all follow up visits as compared to its
baseline. The mean score for severity of dysphagia in Omeprazole group was 1.03
±0.85 at baseline visit, which
reduced significantly to 0.48 ±0.71
on day 7. The mean score for severity of dysphagia further reduced to 0.20 ±0.41 on day 14, 0.10 ±0.30 on day 21 and 0.03 ±0.18 on day 28. There was no
significant difference between the two groups at baseline and on each follow up
visits i.e. between groups effects were
equal.
The mean
score of severity of epigastric pain in Ayucid group was 0.97 ±1.02 on baseline
visit, which reduced significantly to 0.59 ±0.87 on day 7. The mean score of
severity of epigastric pain further reduced to 0.48 ±0.63 on day 14, 0.24 ±0.44
on day 21 and 0.21 ±0.42 on day 28. In Omeprazole group, the mean score of
severity of epigastric pain was 0.87 ±0.82 on baseline visit, which slightly
and insignificantly reduced to 0.80 ±0.82 at the end of 7 days. The reduction
was found to be significant on day 14 (0.20 ±0.41). The mean score of severity
of epigastric pain reduced significantly to 0.29 ±0.46 and 0.17 ±0.38 on day 21
and 28 respectively. The difference between the two groups was however found to
be statistically non-significant i.e. between groups effects were equal.
In Ayucid group, the mean score of nausea
was 1.06 ±0.61 at baseline visit
which reduced significantly to 0.72 ±0.81
on day 7. The severity further reduced to 0.41 ±0.57 on day 14, 0.34 ±0.48
on day 21 and 0.36 ±0.55 on day
28. In Omeprazole group, the reduction in this symptom was also found to be
significant from day 7 and continued further till the end of the study. The
mean score of nausea at baseline was 1.07 ±0.83 which reduced significantly to 0.64 ±0.86, 0.28 ±0.52,
0.14 ±0.36 and 0.13 ±0.35 on day 7, day 14, 21 and 28
respectively. On analysis between the two groups the difference in reduction
was not found to be significant i.e.
between groups effects were equal.
The mean
appetite score at baseline was 5.12 ±1.34 which improved significantly to 5.50
±1.18 on day 7. The mean appetite score further improved to 6.57 ±1.32 on day
14. The mean appetite score was found to be 7 ±1.52 and 7.20 ±1.55 on day 21
and 28 respectively. In Omeprazole group, the mean appetite score was found to
be 4.73 ±1.39 at baseline visit which increased significantly to 5.72 ±1.54 on
day 7, 6.06 ±1.54 on day 14, 6.93 ±2.14
and 7.75 ±2.27 on day 21 and 28 respectively.
It was observed that only one subject
in Ayucid capsule group required the use of rescue medication only once during
the study period.
The mean total heartburn score at
baseline in Ayucid group was 13.36 ±7.24,
which reduced significantly to 5.69 ±5.50
and 2.81 ±2.83 on day 14 and day
28 respectively. In Omeprazole group, the mean total heartburn score at
baseline visit was 12.90 ±7.37
which reduced to 4.32 ±4.94 and
2.14 ±2.12 on day 14 and 28
respectively. The difference between the two groups was however found to be non-significant
i.e. between groups effects were equal.
The mean total
regurgitation score at baseline visit in Ayucid group was 10.58 ±7.38 which
reduced significantly to 4.24 ±4.85 and 1.7 ±2.67 on day 14 and 28 respectively.
The mean total regurgitation score at baseline visit in Omeprazole group was
11.47 ±7.93 which reduced significantly to 3.60 ±4.98 and 1.79 ±2.35 on day 14
and 28 respectively. The difference between the two groups was however found to
be non-significant i.e. between groups effects were equal.
Assessment of
total GERD-HRQOL score was done and it was observed that there was a
significant reduction in the same in both the study groups when compared to its
baseline score. The difference between the two study groups was found to be
non-significant. The mean total GERD-HRQOL score in Ayucid group was 26.48 ±16.60
which reduced significantly to 10.93 ±11.29 and 5 ±5.26 on day 14 and 28 respectively.
The mean GERD-HRQOL score at baseline visit in Omeprazole group was found to be
27.10 ±18.44 which reduced to 8.84 ±11.19 and 4.18 ±4.35 on day 14 and 28 respectively.
It was
observed that 21 (63.63%) subjects had bloating at the baseline visit in Ayucid
group, while on day 14 and 28 only 13 subjects (39.39%) and 12 subjects
(36.36%) complained of this symptom respectively. In Omeprazole group, 17
(56.66%) subjects were having bloating at baseline visit. There were 13
(43.33%) and 9 subjects (30%) who complained of bloating on day 14 and 28
respectively. The difference between these two groups was found to be non-significant.
It was observed
that at the baseline, 18 (54.54%) subjects had constipation in Ayucid group.
There were 9 (27.27%) and 8 subjects (24.24%) who had constipation on day 14
and 28 respectively. In Omeprazole group, 15 (5-%) subjects had constipation at
the baseline visit. There were 7 (23.33%) subjects who had constipation on day
14 and 28. There was no significant difference between the two groups.
It was
observed that a total of 29 (87.87%) subjects had gaseous abdominal distension
at the baseline visit in Ayucid group. There were 19 (57.57%) and 15 (45.45%) subjects
who reported to have gaseous abdominal distension on day 14 and 28 respectively.
In Omeprazole group, gaseous abdominal distension was observed in 25 subjects (83.33%0
at baseline visit. On day 14, 12 subjects reported to have gaseous abdominal
distension and at the end of the study 10 (33.33%) subjects reported to have gaseous
abdominal distension. There was no significant difference between the two
groups.
No
significant change in any of the laboratory parameters and ECG was observed from
baseline to 28 days in both the study groups. The parameters were observed to
be within normal limits both at the baseline and final study visits.
Vital
parameters like pulse rate, respiratory rate, blood pressure and body
temperature were checked at all the visits. It was observed that there was no
significant change in these parameters on all the visits. These parameters were
within normal range at baseline as well as on each follow up visit.
A total of 39
AEs were reported by 25 subjects. Of these 26 AEs were reported in Ayucid group
while 13 AEs were reported in Omeprazole group. Of the 26 AEs reported in
Ayucid group, 20 AEs were not related to the study drug, while 5 AEs were
possibly related to the study drug. These episodes did not require interruption
of the study drug or procedure. Out of these, one adverse drug reaction
(allergic rash) was found in one subject which was definitely related to the
study drug. Also of the 13 AEs reported in Omeprazole group, 11 AEs were
reported as unrelated to the study drug, while 1 AE each was reported as
possible and probably related to the study drug. These episodes did not require
interruption of the study drug or procedure.
It was
observed that 29 (87.87%) subjects reported of much to very much improvement in
Ayucid group while 22 (73.33%) subjects reported much to very much improvement
in omeprazole group. Two subjects (2.06) reported minimal improvement in Ayucid
group while 5 (16.66%) subjects reported minimal improvement in Omeprazole
group at the end of the study. Conclusion:
It can be
concluded from the results that both Ayucid and Omeprazole capsules have shown
significant improvement in the symptoms of GERD like heartburn, acid regurgitation,
nausea, epigastric pain etc. The improvement in both the groups was evident
from 7th day and continued till the end of the study. No significant change in any of the vitals
and laboratory parameters was observed in both the groups. The effect of Ayucid capsules was found to be
equal or non inferior to that of Omeprazole in subjects suffering from GERD. Thus,
Ayucid Capsule is safe and effective in the management of GERD.
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