Introduction
Methods
Design overview
Setting and participants
Randomization and intervention
Outcomes and measurements
Follow-up procedures
Statistical analysis
Role of the funding source
Results
Study patients
Lansoprazole (n = 226) | Gefarnate (n = 235) | |
---|---|---|
Mean age (SD), years | 69.3 (8.57) | 68.7 (8.79) |
Sex | ||
Males | 175 (77.4) | 192 (81.7) |
Females | 51 (22.6) | 43 (18.3) |
Current smoking status | 52 (23.0) | 53 (22.6) |
Alcohol consumption | 102 (45.1) | 123 (52.3) |
Mean duration (SD) of prior LDA (months)a
| 25.4 (13.34) | 24.9 (13.54) |
Status of concomitant aspirin use | ||
Aspirin dialminate | 27 (11.9) | 28 (11.9) |
81 mg | 26 (11.5) | 26 (11.1) |
162 mg | 1 (0.4) | 3 (1.3) |
Aspirin | 199 (88.1) | 207 (88.1) |
100 mg | 193 (85.4) | 194 (82.6) |
200 mg | 7 (3.1) | 13 (5.5) |
Underlying diseaseb
| ||
Ischemic heart disease | 109 (48.2) | 120 (51.1) |
Ischemic stroke | 96 (42.5) | 97 (41.3) |
Others | 50 (22.1) | 49 (20.9) |
H. pylori statusc
| ||
Positive | 137 (60.6) | 125 (53.2) |
Negative | 89 (39.4) | 109 (46.4) |
CYP2C19 polymorphismd
| ||
EM | 163 (72.1) | 181 (77.0) |
PM | 40 (17.7) | 34 (14.5) |
Mean compliance rate (SD), % | ||
Study drug | 99.03 (2.268) | 98.17 (7.073) |
LDA therapy | 93.84 (3.319) | 93.12 (7.400) |
Efficacy
Lansoprazolea (n = 226) | Gefarnateb (n = 234) | Hazard ratio (95% CI) |
P valuec
| |
---|---|---|---|---|
Number at risk at baselined
| 213 | 227 | ||
Primary endpoint | ||||
Gastric or duodenal ulcer | 6 | 53 | 0.099 (0.042–0.230) | <0.001 |
Secondary endpoints | ||||
Gastric/duodenal ulcer or hemorrhagic lesion | 7 | 56 | 0.109 (0.050–0.239) | <0.001 |
Gastric/duodenal ulcer, hemorrhagic lesion or treatment discontinuation due to lack of efficacy | 7 | 59 | 0.104 (0.047–0.228) | <0.001 |
Component | ||||
Gastric ulcer | 6 | 40 | ||
Duodenal ulcer | 0 | 15 | ||
Hemorrhagic lesion | 2 | 9 | ||
Treatment discontinuation due to lack of efficacy | 0 | 4 |
Baseline characteristics | Recorded number of patients with gastric or duodenal ulcer | Cox regression analysis | ||
---|---|---|---|---|
Lansoprazole | Gefarnate | Hazard ratio (95% CI) |
P value | |
H. pylori status | ||||
Positive | 3/128a
| 38/122b
| 0.061 (0.019–0.197) | <0.001 |
Negative | 3/85a
| 15/105b
| 0.206 (0.060–0.710) | 0.02 |
CYP2C19 | ||||
PM | 0/38c
| 9/33d
| 0.000 (0.000 to –e) | – |
EM | 5/155c
| 39/175d
| 0.125 (0.049–0.317) | <0.001 |
Age | ||||
32–64 years | 1/57 | 14/72 | 0.072 (0.009–0.550) | 0.02 |
65–88 years | 5/156 | 39/155 | 0.106 (0.042–0.268) | <0.001 |
Gender | ||||
Male | 5/168 | 43/184 | 0.104 (0.041–0.264) | <0.001 |
Female | 1/45 | 10/43 | 0.082 (0.011–0.643) | 0.02 |
Smoker | ||||
Yes | 1/49 | 16/51 | 0.048 (0.006–0.365) | 0.01 |
No | 5/164 | 37/176 | 0.122 (0.048–0.311) | <0.001 |
Alcohol consumption | ||||
Yes | 4/96 | 24/120 | 0.170 (0.059–0.491) | 0.01 |
No | 2/117 | 29/107 | 0.052 (0.012–0.219) | <0.001 |
Concomitant use of anticoagulants | ||||
Yes | 2/47 | 19/69 | 0.127 (0.029–0.546) | 0.01 |
No | 4/166 | 34/158 | 0.091 (0.032–0.256) | <0.001 |
Baseline characteristics | Direction estimation | Multivariate analysis | |
---|---|---|---|
Hazard ratio (95% CI) |
P value | ||
Treatment group | Lansoprazole/gefarnate | 0.085 (0.034–0.216) | <0.001 |
H. pylori status | Positive/negative | 2.057 (1.137–3.720) | 0.02 |
CYP2C19 | PM/EM | 1.434 (0.668–3.076) | 0.36 |
Age | 10 years’ increase | 1.459 (1.045–2.036) | 0.03 |
Gender | Male/female | 0.893 (0.437–1.823) | 0.76 |
Smoking status | Yes/no | 1.532 (0.820–2.863) | 0.19 |
Alcohol consumption | Yes/no | 1.047 (0.588–1.866) | 0.88 |
Concomitant use of anticoagulants | Yes/no | 1.200 (0.665–2.166) | 0.55 |
Adverse events
Adverse events that occurred in the double-blind period | Lansoprazole (n = 226) | Gefarnate (n = 234) |
P value |
---|---|---|---|
All adverse events | 166 (73.5) | 168 (71.8) | 0.70 |
Causal relationship to drug not deniable | 26 (11.5) | 25 (10.7) | 0.78 |
Leading to discontinuations | 21 (9.3) | 24 (10.3) | 0.73 |
Serious adverse events | 27 (11.9) | 26 (11.1) | 0.78 |
Causal relationship to drug not deniable | 0 (0.0) | 1 (0.4) | 0.33 |
Deaths | 0 (0.0) | 0 (0.0) | – |
Adverse events reported in at least 3% of the total in each group | |||
Nasopharyngitis | 54 (23.9) | 55 (23.5) | 0.93 |
Constipation | 14 (6.2) | 8 (3.4) | 0.17 |
Fall | 13 (5.8) | 9 (3.8) | 0.34 |
Diarrhea | 19 (8.4) | 2 (0.9) | <0.001 |
Reflux esophagitis | 3 (1.3) | 16 (6.8) | 0.01 |
Back pain | 10 (4.4) | 5 (2.1) | 0.17 |
Elevated blood creatine phosphokinase levels | 7 (3.1) | 8 (3.4) | 0.85 |
Eczema | 5 (2.2) | 7 (3.0) | 0.61 |
Hypertension | 7 (3.1) | 3 (1.3) | 0.19 |
Adverse events reported in patients who received lansoprazole throughout the double-blind and open-label study | Lansoprazole (n = 339) | ||
---|---|---|---|
All adverse events | 279 (82.3) | ||
Causal relationship to drug not deniable | 55 (16.2) | ||
Leading to discontinuations | 39 (11.5) | ||
Serious adverse events | 51 (15.0) | ||
Causal relationship to drug not deniable | 1 (0.3) | ||
Deaths | 2 (0.6) | ||
Adverse events reported in at least 3% of the total in each group | |||
Nasopharyngitis | 113 (33.3) | ||
Diarrhea | 32 (9.4) | ||
Constipation | 23 (6.8) | ||
Fall | 19 (5.6) | ||
Hypertension | 17 (5.0) | ||
Elevated blood creatine phosphokinase levels | 16 (4.7) | ||
Back pain | 16 (4.7) |