Aliment. Pkarmacol. Tkerap. (1990) 4, 97-99
Duodenal ulcer healing on 2 g of sucravate daily at bedtime compared to z g four times daily
F. BENDTSEN, N. EBBEHBJ, J. FALLINGBORG, K. ABILDGAARD, P. BRBBECH MORTENSEN, P. MATZEN, E. KRAG & H. KROMANN-ANDERSEN Departments of Medical and Surgical Gasfroenferology,Hvidovre Hospifal, Universify of Copenhagen, and Deparfmenf of Medical Gastroenterology, Aalborg Sygehus Nord Accepted for publication 28 July 1989
SUMMARY
Seventy-seven patients with endoscopically verified duodenal ulcers were randomized to treatment with either 2 g sucralfate daily at bedtime or I g sucralfate q.d.s. in a controlled double-blind comparative study. After a 4-week treatment period, the healing rate was 68% for the former and 69% for the latter treatment. INTRODUCTION In duodenal ulcer healing, 1 g sucralfate ingested q.d.~.'-~ or 2 g b.d.,4is as effective as H,-receptor blockers. Furthermore, the latter compounds are equipotent, whether administered as a single dose at bedtime or given twice d a i l ~ .We ~ , therefore ~ found it of interest to investigate whether sucralfate administered as a single dose of 2 g at bedtime would be as effective as sucralfate administered 1 g q.d.s. in duodenal ulcer healing.
Correspondence to : Dr F. Bendtsen, Department of Medical Gastroenterology 261, Hvidovre Hospital, DK-2650 Hvidovre, Denmark. 97
98
F.BENDTSEN ef al.
MATERIAL A N D M E T H O D S
Patienfs Seventy-seven patients (46 men and 31 women, mean age 52 years; range 26-74 years) entered the study. Entry criteria for the study were at least one endoscopically verified duodenal ulcer with a size of at least 5 mm. Each patient gave informed consent and the trial was approved by the local ethics committee. Study design Patients were randomly assigned to treatment with either 1 g of sucralfate taken 1 h before each of three daily meals and 1 g at bedtime or 2 g of sucralfate taken at bedtime. Inactive tablets, identical in appearance to the active tablets, were prepared, so that all the patients received the same number of tablets. Symptoms and antacid intake were registered at entry and after a 4-week treatment period. Any patient who did not take the active drug for 5 days or more was regarded as a dropout. The patients were endoscoped 28-33 days after entry into the study.
Statistical methods Fisher's exact test or two-sample t-test for pretreatment comparisons and healing rates were used. RESULTS Seven patients did not complete the study. Thirty-eight of the 70 patients who completed the study received 2 g sucralfate at bedtime and 32 patients were treated with 1 g sucralfate q.d.s. The overall healing rate was 69% (95 YOconfidence intervals 51.4-82.5%) in the group treated four times daily and 68% (95 % confidence interval 50.0-83.9%) in the group treated once daily (Table I). Table 1. Healing rates of duodenal ulcers on 2 g sucralfate at bedtime versus 1 g four times daily Sucralfate 2 g at bedtime
1 g q.d.s.
Total
P
Healed Unhealed Total
26 12 35
22 10 32
48 22
NS NS
Healed (%)
65.4 (51.4-82.5)
65.5 (50.0-53.9)
65.6
NS
Confidence intervals (95 %) are in parentheses.
D U HEALING BY SUCRALFATE
99
No difference was observed in symptoms between the two groups, either at entrance or at the end of the 4-week treatment period.
DISCUSSION Sucralfate, given as a single dose daily at bedtime, has never previously been evaluated as therapy in active duodenal ulcers. We €ound a healing rate of approximately 70 % for both therapies and an almost identical effect on symptoms. The results must, however, be taken with some precaution as only 70 patients completed the study. The risk of a type-two error may be overlooked, although the close difference in healing rates reduces the risk of a type-two error substantially. However, our findings should encourage further investigations on sucralfate administered as a single dose at bedtime. ACKNOWLEDGEMENTS
The sucralfate and placebo tablets were kindly provided by Farmos A/S, Glostrup, Denmark. REFERENCES 1 Martin F, Farley A, Gagnon M, Bensemana
D. Comparison of the healing capacities of sucralfate and cimetidine in the short term of duodenal ulcer: a double-blind randomized trial. Gastroenterology 1982; 82: 401-5. 2 Hollander D. A multicenter, double-blind trial of sucralfate in duodenal ulcer therapy. Scand J Gastroenterol 1983; 18: (Suppl. 83) 25-30. 3 Glise H, Carling M D, Hallerback B et al. Treatment of acute duodenal ulcer - a Swedish multicenter study. Scand J Gastroenterol 1987; 22: (Suppl. 127) 61-6.
4 Marks I N, Wright J P, Glinsky N H et al. Comparison of sucralfate dosage schedule in duodenal ulcer. Two grams twice a day versus one gram four times a day. J Clin Gasfroenterol 1986; 8: 419-23. 5 Capurso L, Monte P R D, Mazzeo F et al. Comparison of cimetidine 800 mg once daily and 400 mg twice daily in acute duodenal ulceration. Br Med J 1984; 84: 1418-20. 6 Kildebo S, Aronsen 0, Bernersen B et al. Cimetidine 800 mg at night, in the treatment of duodenal ulcers. Scand J Gastroenterol 1985; 20: 1147-50.
Duodenal ulcer healing on 2 g of sucravate daily at bedtime compared to z g four times daily
F. BENDTSEN, N. EBBEHBJ, J. FALLINGBORG, K. ABILDGAARD, P. BRBBECH MORTENSEN, P. MATZEN, E. KRAG & H. KROMANN-ANDERSEN Departments of Medical and Surgical Gasfroenferology,Hvidovre Hospifal, Universify of Copenhagen, and Deparfmenf of Medical Gastroenterology, Aalborg Sygehus Nord Accepted for publication 28 July 1989
SUMMARY
Seventy-seven patients with endoscopically verified duodenal ulcers were randomized to treatment with either 2 g sucralfate daily at bedtime or I g sucralfate q.d.s. in a controlled double-blind comparative study. After a 4-week treatment period, the healing rate was 68% for the former and 69% for the latter treatment. INTRODUCTION In duodenal ulcer healing, 1 g sucralfate ingested q.d.~.'-~ or 2 g b.d.,4is as effective as H,-receptor blockers. Furthermore, the latter compounds are equipotent, whether administered as a single dose at bedtime or given twice d a i l ~ .We ~ , therefore ~ found it of interest to investigate whether sucralfate administered as a single dose of 2 g at bedtime would be as effective as sucralfate administered 1 g q.d.s. in duodenal ulcer healing.
Correspondence to : Dr F. Bendtsen, Department of Medical Gastroenterology 261, Hvidovre Hospital, DK-2650 Hvidovre, Denmark. 97
98
F.BENDTSEN ef al.
MATERIAL A N D M E T H O D S
Patienfs Seventy-seven patients (46 men and 31 women, mean age 52 years; range 26-74 years) entered the study. Entry criteria for the study were at least one endoscopically verified duodenal ulcer with a size of at least 5 mm. Each patient gave informed consent and the trial was approved by the local ethics committee. Study design Patients were randomly assigned to treatment with either 1 g of sucralfate taken 1 h before each of three daily meals and 1 g at bedtime or 2 g of sucralfate taken at bedtime. Inactive tablets, identical in appearance to the active tablets, were prepared, so that all the patients received the same number of tablets. Symptoms and antacid intake were registered at entry and after a 4-week treatment period. Any patient who did not take the active drug for 5 days or more was regarded as a dropout. The patients were endoscoped 28-33 days after entry into the study.
Statistical methods Fisher's exact test or two-sample t-test for pretreatment comparisons and healing rates were used. RESULTS Seven patients did not complete the study. Thirty-eight of the 70 patients who completed the study received 2 g sucralfate at bedtime and 32 patients were treated with 1 g sucralfate q.d.s. The overall healing rate was 69% (95 YOconfidence intervals 51.4-82.5%) in the group treated four times daily and 68% (95 % confidence interval 50.0-83.9%) in the group treated once daily (Table I). Table 1. Healing rates of duodenal ulcers on 2 g sucralfate at bedtime versus 1 g four times daily Sucralfate 2 g at bedtime
1 g q.d.s.
Total
P
Healed Unhealed Total
26 12 35
22 10 32
48 22
NS NS
Healed (%)
65.4 (51.4-82.5)
65.5 (50.0-53.9)
65.6
NS
Confidence intervals (95 %) are in parentheses.
D U HEALING BY SUCRALFATE
99
No difference was observed in symptoms between the two groups, either at entrance or at the end of the 4-week treatment period.
DISCUSSION Sucralfate, given as a single dose daily at bedtime, has never previously been evaluated as therapy in active duodenal ulcers. We €ound a healing rate of approximately 70 % for both therapies and an almost identical effect on symptoms. The results must, however, be taken with some precaution as only 70 patients completed the study. The risk of a type-two error may be overlooked, although the close difference in healing rates reduces the risk of a type-two error substantially. However, our findings should encourage further investigations on sucralfate administered as a single dose at bedtime. ACKNOWLEDGEMENTS
The sucralfate and placebo tablets were kindly provided by Farmos A/S, Glostrup, Denmark. REFERENCES 1 Martin F, Farley A, Gagnon M, Bensemana
D. Comparison of the healing capacities of sucralfate and cimetidine in the short term of duodenal ulcer: a double-blind randomized trial. Gastroenterology 1982; 82: 401-5. 2 Hollander D. A multicenter, double-blind trial of sucralfate in duodenal ulcer therapy. Scand J Gastroenterol 1983; 18: (Suppl. 83) 25-30. 3 Glise H, Carling M D, Hallerback B et al. Treatment of acute duodenal ulcer - a Swedish multicenter study. Scand J Gastroenterol 1987; 22: (Suppl. 127) 61-6.
4 Marks I N, Wright J P, Glinsky N H et al. Comparison of sucralfate dosage schedule in duodenal ulcer. Two grams twice a day versus one gram four times a day. J Clin Gasfroenterol 1986; 8: 419-23. 5 Capurso L, Monte P R D, Mazzeo F et al. Comparison of cimetidine 800 mg once daily and 400 mg twice daily in acute duodenal ulceration. Br Med J 1984; 84: 1418-20. 6 Kildebo S, Aronsen 0, Bernersen B et al. Cimetidine 800 mg at night, in the treatment of duodenal ulcers. Scand J Gastroenterol 1985; 20: 1147-50.
