Reflux Esophagitis Therapy: Sucralfate Versus Ranitidine in a Double Blind Multicenter Trial CEDRIC G. BREMNER, M.B., Johannesburg, south Africa, I.N. MARKS, M.B., Cape TOWS, SOU~/I Africa, ISADORESEGAL, M.B., Johannesburg, South Africa, AHMED SIMJEE, M.B., Durban, South Africa
Sucralfate (SC) suspension 6 g/day and ranitidine (Rn) tablets, 150 mg, were compared in 125 patients in a double-blind, multicenter, endoscopically controlled trial in the treatment of reflux esophagitis. Inclusion criteria were symptomatic reflux (number and severity of attacks) and endoscopic evidence of esophagitis (grades 1 to 4). Clinical assessments were performed on entry, and at 4 and at 8 weeks, and endoscopy was repeated at 8 weeks. SC suspension and Rn placebo or SC placebo and Rn tablets were taken on waking and immediately before retiring at night. Of the 125 patients, 27 were withdrawn because of default (Rn = 4; SC = 141, noncompliance (Rn = 1; SC = 21, or the development of congestive cardiac failure (Rn = 11, diarrhea (Rn = 1; SC = 11, nausea (SC = l), constipation (SC = 11, and hematemesis (SC = 1). Analysis was performed on the remaining 98 patients, 43 of whom had been treated with SC and 55 with Rn. Heartburn, acid regurgitation, epigastric pain, dysphagia, and chest pain were relieved in 34% vs 40%, 67% vs 72%, 71% vs 57%, and 86% vs 63% for SC and Rn, respectively. There was no significant difference between the two groups. Endoscopic healing occurred in 47% of the SC- and in 31% of the Rn-treated patients (2 = 2.50), and healing or improvement was noted in 81% of the SC- and 64% of the Rn-treated patients. This difference approached statistical significance (,$ = 3.73). There was no obvious endoscopic benefit in 8 of the 43 and 20 of the 55 patients in the groups treated with SC and Rn, respectively. Although the findings with sucralfate and ranitidine in patients with reflux esophagitis completing the trial suggest a benefit of these agents, the absence of a placebo control group and the high default rates, particularly for
Fromthe Universitiesof Witwatersrand,Cape Town, Natal, South Africa. Requests for reprints should be addressed to Cedric G. Bremner, Department of Surgery, Medical School, University of Witwatersrand, 7 York Road, Parktown 2193, Johannesburg, South Africa.
August 8,
those receiving sucralfate, preclude any firm conclusions as to relative or specific efficacy of these agents in this condition.
he availability of new classesof drugs in the T last decadehas improved the results of treatment of reflux esophagitis.These drugs act by either suppressingacid peptic activity (histamine-2 [Hal-receptor and proton pump antagonists), increasing mucosal protection (sucralfate [SC]), or enhancingmotility (prokinetics). Normal dosesof either Hz-receptorantagonistsor SCare reported to give symptomatic and endoscopicimprovement in reflux esophagitis[1,2]. In this double-blinded, controlled trial, the Ha-receptorantagonistranitidine (Rn) was comparedwith SCsuspensionin the treatment of reflux esophagitis. MATERIALAND METHODS A total of 125 patients from four units in three centers (CapeTown, Johannesburg,Durban) were entered into the study. Patients who had previous gastric or esophagealsurgery or who had serious pulmonary, cardiac, or renal disease were excluded. All patients were given the option to withdraw from the trial if they wished. Inclusion criteria were symptomatic reflux and endoscopicevidenceof esophagitis.Permission from the Human Ethics Committee of each center was granted for this study. Symptomatic patients were graded endoscopitally into grade 0 (normal mucosa),grade la (erythema), lb (erosions or exudate), grade 2 (noncircumferential confluent erosions and exudate), grade 3 (circumferential erosions and exudate), grade 4a (chronic mucosal ulceration), grade 4b (chronic mucosal stricture) and grade 4c (other chronic mucosal lesions such as Barrett’s esophagus, brachyesophagus).Patients with strictures were dilated to a minimum of 40F before treatment. Symptoms of heartburn, acid regurgitation, epigastric pain, dysphagia, or chest pain were recorded on a daily basis by the patient. SCsuspension (6 g/m30 ml/day) and Rn tablets (150 mg b.i.d.) were given by a double-blind method. The
1991 The American Journal of Medicine
Volume 91 (suppl 2A)
2A-119s
SYMPOSIUM ON SUCRALFATE / BREMNER ET AL
cardiac failure (Rn = l), diarrhea (Rn = 1, Sc = l), nausea (Sc = l), constipation (Se = l), or Patient Characteristics I hematemesis (SC = 1). Analysis was carried out on the remaining 98 patients, 43 of whom had been Sucralfate Ranitidine (n=43) (n = 55) treated with sucralfate and 55 with ranitidine. The patient characteristics are detailed in Table I. Male Female ;i ;i Heartburn, acid regurgitation, epigastric pain, dysAge phagia, and chest pain were completely relieved in 60 years 63% for SC and Rn, respectively (Table II). None of Smoking Light (~20 cigarettes/day) these changes showed statistical significance. SigHeavy (>20 cigarettes/day) nificant changes in symptom severity were noted Alcohol ~50 g/day 10 after treatment with either medicine. Although >50 g/day s 1 there was no difference in the complete relief of Du~pna4f symptoms 10 dysphagia in the two groups, reduction in the numl-2 years 1’; ber of daily dysphagia symptoms was significantly i 2-3 years 3 yearst 20 2; better in the Ulsanic group (standard deviation NSAIDintake 5 1.63; p = 0.03). There was no difference in the Steroid intake i Hiatal hernia ii 32 overall relief of heartburn, epigastric, or acid re, SAID = nonsteroidal anti-inflammatory drug. gurgitation between the two groups. Endoscopic healing occurred in 47% of the SC and in 31% of the Rn-treated patients (2 = 2.50), and healing or improvement was noted in 81% of the SC TABLE II I and 64% of the Rn-treated patients (Table III). Complete Symptomatic Relief by Sucralfate or Ranitidine I There was no obvious endoscopic benefit in 8 of 43 No. Relieved by No. Relieved by and 20 of 55 patients in the SC- and Rn-treated Sucralfate % Ranitidine % pValue Symptom groups, respectively. There was also no statistical Heartburn 14141 21152 0.688 difference in the healing rates in the two groups when grade 4 esophagitis (stricture) was excluded Acid regurgitation 20130 ii.6 26/36 ;; Ed Epigastric Dysphwpain 23132 12114 l.7 26145 12119 ii 0.297 from the analysis (p = 0.129). TABLE I
416
Chest pain
216
0.564
COMMENTS active or placebo tablet was taken first and was followed by a cup of water and then by the active or placebo suspension. Medicines were taken on waking in the morning and immediately before going to sleep at night. All patients completed diary cards regarding symptoms. Clinical assessments were carried out on entry, at 4 weeks, and at 8 weeks, and endoscopy was repeated at 8 weeks. Symptom responses were analyzed in 2 days. Complete symptomatic relief of the five symptoms was compared in the two groups (2 and Fisher analysis). In a second analysis, a point scoring system was used to compare changes in the severity and frequency of symptoms (Zsample t-test on each variable). Endoscopic changes were classified into those that were healed, improved, unchanged, or worse (2 analysis).
RESULTS Of the 125 patients, 27 were withdrawn because of default (Rn = 4, SC = 14), noncompliance (Rn = 1, SC = 2), or the development of congestive
2A42os
August 8,
1991
The American Journal of Medicine
Volume
91
The two drugs tested have different modes of action. Ranitidine, an Hz-receptor blocker, reduces the gastric acid output and thereby also reduces the amount of gastric acid available for reflux. Sucralfate, on the other hand, binds with proteins in areas of mucosal lesions (thus providing mechanical protection), stimulates tissue prostaglandin production, and absorbs bile acids [3]. Both drugs have been shown to improve symptoms and endoscopitally proven reflux esophagitis. In the current study, complete relief of symptoms was noted in 34-85% of patients, using either medicine and depending on which symptom was evaluated. Complete relief of heartburn was accomplished in only 34% and 40% of cases for SC and Rn, respectively, whereas better relief of the other symptoms was documented. In both regimens the improvement noted was statistically significant for all symptoms. Complete endoscopically proven healing occurred in less than half of each group, but healing or improvement was noted in 81% of the SC and 64% of the Rn groups (difference not signifi-
(suppl 2A)
SYMPOSIUM
ON SUCRALFATE I BREMNER ET AL
TABLE III Endoscopic Healing After Treatment with Ranitidine (R) and Sucralfate (SC) Total
Healed
Improved
Same
Worse
Grade
RII
SC
Rn
SC
Rn
SC
Rn
SC
Rn
SC
:
:t
23 11
11 5
15 4
:
3
10 1
3
2
2
:
4
:
1
1
3
:
6
T
i
-
43
17
i
7
Total Pvalue, all grades P value, grades l-3
5:
ii
1:
0.114 0.137
0.823 0.839
cant). These results are similar to those reviewed by Tytgat [l], in which endoscopic healing or improvement took place in up to 91% of cases using sucralfate or ranitidine. However, in the absence of a true placebo group, the improvements noted for each medication in the current study, although likely to reflect a beneficial response, cannot be considered conclusive evidence of a beneficial effect. The considerable default rate (Rn = 4/55; SC = 14/43) in this study is not explained. Six of these patients defaulted only after the 4-week visit and further supply of medication (5 SC; 1 Rn). Not one of these patients complained of the medication at the 4-week visit, and all were improved symptomatically. Default was not related to the severity of the esophagitis because most of these patients had grade 1 esophagitis and there were only two grade 3 lesions and one grade 2 lesion in this group. In a review of eight clinical trials that reported on the use of ranitidine (150 mg b.i.d.), there was a 47% endoscopic healing rate [2]. Increasing the ranitidine dose to 300 mg b.i.d. did not improve the results in the average patient [4,5]. Better healing rates (up to 78%) have been reported when isolated erosions were present as opposed to a healing rate of only 23% when confluent erosions were present 161. In a multicenter study reported by Williams et al [7], sucralfate, given in a suspension at dosages of 1 g/10 mL three times daily after meals and 2 g/20 mL at bedtime for 8 weeks, resulted in complete healing in 36% of patients and improvement in 45%, but these results were no better than those found with placebo. They suggest that 12 weeks’ treatment may be preferable, because Weiss et al 181reported a 72% complete endoscopic healing rate after 3 months’ treatment with sucralfate when alginate was supplemented for symptomatic control. Simon and Mueller [9] also compared the effect of sucralfate and ranitidine in reflux esophagitis. As in our study, the greater the degree of severity of re-
August 8,
1:
17
0.049 0.120
2
0.858 0.129
flux esophagitis, the lower were the chances of complete healing. Both forms of treatment, given in doses of 1 g sucralfate, four times daily, or ranitidine, 150 mg b.i.d., also gave similar results. Reflux esophagitis was healed in 14 of 22 patients treated with sucralfate and 13 of 19 when ranitidine was used for 8 weeks. The greater improvement in their study is explained by the larger number of patients in whom the esophagitis was in stage 1. Whether larger doses of either drug would have been more beneficial is also debatable. There are reports of better healing rates with each drug when patients are evaluated after 3 and 6 months of treatment [4]. As in the study reported by Koelz et aE [61, age, sex, duration of history, and alcohol consumption did not seem to affect the outcome in the two groups. An unfavorable effect in smokers was noted in the report of Koelz et al, but there was no difference in our two groups. Either drug proved to be safe, with few side effects. The default rates were believed to be due to a reluctance on the part of patients to undergo a second endoscopy at the conclusion of the trial. In conclusion, both ranitidine and sucralfate are safe drugs and appear to result in a significant improvement in reflux esophagitis. Both drugs also appear to be more effective in stages 1 and 2 reflux esophagitis, but gave disappointing results in more serious esophagitis. Because the drugs have different modes of action, and because both have similar effects, a combination therapy of the two drugs used for a longer period may prove to be more effective than each drug used separately. Although, as indicated, the findings with sucralfate and ranitidine in patients with reflux esophagitis completing the trial suggest a benefit of these agents, the absence of a placebo control group and the high default rates, particularly for those receiving sucralfate, preclude any firm conclusions as to relative or specific efficacy of these agents in this condition.
1991
The American Journal of Medicine
Volume 91 (suppl 2A)
2A421s
SYMPOSIUM ON SUCRALFATE / BREMNER ET AL
REFERENCES 1. Tytgat GNJ. Clinical efficacy of sucralfate in reflux esophagitis. Comparison with cimetidine Am J Med 1987; 83 (Suppl 38): 38-42. 2. Koelz HR. Treatment of reflux esophagitis with He blockers, antacids and prokinetic drugs. An analysis of randomized clinical trials. Stand J Gastroenterol 1989; 24 (suppl 156): 25-36. 3. Konturek SJ, Kwiecien N, Obtulowicz W, Kopp B, Olesky J. Double blind controlled study on the effect of sucralfate on gastric prostaglandin formation and microbleeding in normal and aspirin-treated man. Gut 1986; 27: 1450-6. 4. Meuwissen SGM, KlrnkenbergKnol EC. Treatment of reflux oesophagitis with Ha receptor antagonists. Stand J Gastroenterol 1988; 23 (Suppl 146): 201-13.
2HZ2S
August 8, 1991
The American Journal of Medicine
5. Bianchi PG, Pace F, Lazzaroni M Esophagitis healing with ranitidine. Gastroenterology 1987; 92: 2051-2. 6. Koelz HR, Birchler R, Bretholz A, et al. Healing and relapse of reflux esophagitis during treatment with ranitidine. Gastroenterology 1986; 91; 1198-205. 7. Willrams RM, Orlando RC, Bozymski EM, et al. Multicenter trial of sucralfate suspension for the treatment of reflux esophagitis. Am J Med 1987; 83 (Suppl 38): 61-6. 8. Weiss W, Brunner H, BiXtner GR, et al. Therapie deur refluxosophagitis sucralfat. Dtsch Med Wochenschr 1983; 108: 1706-11.
mit
9. Simon B, Mueller P. Comparison of the effect of sucralfate and ranitidine in reflux esophagitis. Am J Med 1987; 83 (Suppi 38): 43-7.
Volume 91 (suppl 2A)
Sucralfate (SC) suspension 6 g/day and ranitidine (Rn) tablets, 150 mg, were compared in 125 patients in a double-blind, multicenter, endoscopically controlled trial in the treatment of reflux esophagitis. Inclusion criteria were symptomatic reflux (number and severity of attacks) and endoscopic evidence of esophagitis (grades 1 to 4). Clinical assessments were performed on entry, and at 4 and at 8 weeks, and endoscopy was repeated at 8 weeks. SC suspension and Rn placebo or SC placebo and Rn tablets were taken on waking and immediately before retiring at night. Of the 125 patients, 27 were withdrawn because of default (Rn = 4; SC = 141, noncompliance (Rn = 1; SC = 21, or the development of congestive cardiac failure (Rn = 11, diarrhea (Rn = 1; SC = 11, nausea (SC = l), constipation (SC = 11, and hematemesis (SC = 1). Analysis was performed on the remaining 98 patients, 43 of whom had been treated with SC and 55 with Rn. Heartburn, acid regurgitation, epigastric pain, dysphagia, and chest pain were relieved in 34% vs 40%, 67% vs 72%, 71% vs 57%, and 86% vs 63% for SC and Rn, respectively. There was no significant difference between the two groups. Endoscopic healing occurred in 47% of the SC- and in 31% of the Rn-treated patients (2 = 2.50), and healing or improvement was noted in 81% of the SC- and 64% of the Rn-treated patients. This difference approached statistical significance (,$ = 3.73). There was no obvious endoscopic benefit in 8 of the 43 and 20 of the 55 patients in the groups treated with SC and Rn, respectively. Although the findings with sucralfate and ranitidine in patients with reflux esophagitis completing the trial suggest a benefit of these agents, the absence of a placebo control group and the high default rates, particularly for
Fromthe Universitiesof Witwatersrand,Cape Town, Natal, South Africa. Requests for reprints should be addressed to Cedric G. Bremner, Department of Surgery, Medical School, University of Witwatersrand, 7 York Road, Parktown 2193, Johannesburg, South Africa.
August 8,
those receiving sucralfate, preclude any firm conclusions as to relative or specific efficacy of these agents in this condition.
he availability of new classesof drugs in the T last decadehas improved the results of treatment of reflux esophagitis.These drugs act by either suppressingacid peptic activity (histamine-2 [Hal-receptor and proton pump antagonists), increasing mucosal protection (sucralfate [SC]), or enhancingmotility (prokinetics). Normal dosesof either Hz-receptorantagonistsor SCare reported to give symptomatic and endoscopicimprovement in reflux esophagitis[1,2]. In this double-blinded, controlled trial, the Ha-receptorantagonistranitidine (Rn) was comparedwith SCsuspensionin the treatment of reflux esophagitis. MATERIALAND METHODS A total of 125 patients from four units in three centers (CapeTown, Johannesburg,Durban) were entered into the study. Patients who had previous gastric or esophagealsurgery or who had serious pulmonary, cardiac, or renal disease were excluded. All patients were given the option to withdraw from the trial if they wished. Inclusion criteria were symptomatic reflux and endoscopicevidenceof esophagitis.Permission from the Human Ethics Committee of each center was granted for this study. Symptomatic patients were graded endoscopitally into grade 0 (normal mucosa),grade la (erythema), lb (erosions or exudate), grade 2 (noncircumferential confluent erosions and exudate), grade 3 (circumferential erosions and exudate), grade 4a (chronic mucosal ulceration), grade 4b (chronic mucosal stricture) and grade 4c (other chronic mucosal lesions such as Barrett’s esophagus, brachyesophagus).Patients with strictures were dilated to a minimum of 40F before treatment. Symptoms of heartburn, acid regurgitation, epigastric pain, dysphagia, or chest pain were recorded on a daily basis by the patient. SCsuspension (6 g/m30 ml/day) and Rn tablets (150 mg b.i.d.) were given by a double-blind method. The
1991 The American Journal of Medicine
Volume 91 (suppl 2A)
2A-119s
SYMPOSIUM ON SUCRALFATE / BREMNER ET AL
cardiac failure (Rn = l), diarrhea (Rn = 1, Sc = l), nausea (Sc = l), constipation (Se = l), or Patient Characteristics I hematemesis (SC = 1). Analysis was carried out on the remaining 98 patients, 43 of whom had been Sucralfate Ranitidine (n=43) (n = 55) treated with sucralfate and 55 with ranitidine. The patient characteristics are detailed in Table I. Male Female ;i ;i Heartburn, acid regurgitation, epigastric pain, dysAge phagia, and chest pain were completely relieved in 60 years 63% for SC and Rn, respectively (Table II). None of Smoking Light (~20 cigarettes/day) these changes showed statistical significance. SigHeavy (>20 cigarettes/day) nificant changes in symptom severity were noted Alcohol ~50 g/day 10 after treatment with either medicine. Although >50 g/day s 1 there was no difference in the complete relief of Du~pna4f symptoms 10 dysphagia in the two groups, reduction in the numl-2 years 1’; ber of daily dysphagia symptoms was significantly i 2-3 years 3 yearst 20 2; better in the Ulsanic group (standard deviation NSAIDintake 5 1.63; p = 0.03). There was no difference in the Steroid intake i Hiatal hernia ii 32 overall relief of heartburn, epigastric, or acid re, SAID = nonsteroidal anti-inflammatory drug. gurgitation between the two groups. Endoscopic healing occurred in 47% of the SC and in 31% of the Rn-treated patients (2 = 2.50), and healing or improvement was noted in 81% of the SC TABLE II I and 64% of the Rn-treated patients (Table III). Complete Symptomatic Relief by Sucralfate or Ranitidine I There was no obvious endoscopic benefit in 8 of 43 No. Relieved by No. Relieved by and 20 of 55 patients in the SC- and Rn-treated Sucralfate % Ranitidine % pValue Symptom groups, respectively. There was also no statistical Heartburn 14141 21152 0.688 difference in the healing rates in the two groups when grade 4 esophagitis (stricture) was excluded Acid regurgitation 20130 ii.6 26/36 ;; Ed Epigastric Dysphwpain 23132 12114 l.7 26145 12119 ii 0.297 from the analysis (p = 0.129). TABLE I
416
Chest pain
216
0.564
COMMENTS active or placebo tablet was taken first and was followed by a cup of water and then by the active or placebo suspension. Medicines were taken on waking in the morning and immediately before going to sleep at night. All patients completed diary cards regarding symptoms. Clinical assessments were carried out on entry, at 4 weeks, and at 8 weeks, and endoscopy was repeated at 8 weeks. Symptom responses were analyzed in 2 days. Complete symptomatic relief of the five symptoms was compared in the two groups (2 and Fisher analysis). In a second analysis, a point scoring system was used to compare changes in the severity and frequency of symptoms (Zsample t-test on each variable). Endoscopic changes were classified into those that were healed, improved, unchanged, or worse (2 analysis).
RESULTS Of the 125 patients, 27 were withdrawn because of default (Rn = 4, SC = 14), noncompliance (Rn = 1, SC = 2), or the development of congestive
2A42os
August 8,
1991
The American Journal of Medicine
Volume
91
The two drugs tested have different modes of action. Ranitidine, an Hz-receptor blocker, reduces the gastric acid output and thereby also reduces the amount of gastric acid available for reflux. Sucralfate, on the other hand, binds with proteins in areas of mucosal lesions (thus providing mechanical protection), stimulates tissue prostaglandin production, and absorbs bile acids [3]. Both drugs have been shown to improve symptoms and endoscopitally proven reflux esophagitis. In the current study, complete relief of symptoms was noted in 34-85% of patients, using either medicine and depending on which symptom was evaluated. Complete relief of heartburn was accomplished in only 34% and 40% of cases for SC and Rn, respectively, whereas better relief of the other symptoms was documented. In both regimens the improvement noted was statistically significant for all symptoms. Complete endoscopically proven healing occurred in less than half of each group, but healing or improvement was noted in 81% of the SC and 64% of the Rn groups (difference not signifi-
(suppl 2A)
SYMPOSIUM
ON SUCRALFATE I BREMNER ET AL
TABLE III Endoscopic Healing After Treatment with Ranitidine (R) and Sucralfate (SC) Total
Healed
Improved
Same
Worse
Grade
RII
SC
Rn
SC
Rn
SC
Rn
SC
Rn
SC
:
:t
23 11
11 5
15 4
:
3
10 1
3
2
2
:
4
:
1
1
3
:
6
T
i
-
43
17
i
7
Total Pvalue, all grades P value, grades l-3
5:
ii
1:
0.114 0.137
0.823 0.839
cant). These results are similar to those reviewed by Tytgat [l], in which endoscopic healing or improvement took place in up to 91% of cases using sucralfate or ranitidine. However, in the absence of a true placebo group, the improvements noted for each medication in the current study, although likely to reflect a beneficial response, cannot be considered conclusive evidence of a beneficial effect. The considerable default rate (Rn = 4/55; SC = 14/43) in this study is not explained. Six of these patients defaulted only after the 4-week visit and further supply of medication (5 SC; 1 Rn). Not one of these patients complained of the medication at the 4-week visit, and all were improved symptomatically. Default was not related to the severity of the esophagitis because most of these patients had grade 1 esophagitis and there were only two grade 3 lesions and one grade 2 lesion in this group. In a review of eight clinical trials that reported on the use of ranitidine (150 mg b.i.d.), there was a 47% endoscopic healing rate [2]. Increasing the ranitidine dose to 300 mg b.i.d. did not improve the results in the average patient [4,5]. Better healing rates (up to 78%) have been reported when isolated erosions were present as opposed to a healing rate of only 23% when confluent erosions were present 161. In a multicenter study reported by Williams et al [7], sucralfate, given in a suspension at dosages of 1 g/10 mL three times daily after meals and 2 g/20 mL at bedtime for 8 weeks, resulted in complete healing in 36% of patients and improvement in 45%, but these results were no better than those found with placebo. They suggest that 12 weeks’ treatment may be preferable, because Weiss et al 181reported a 72% complete endoscopic healing rate after 3 months’ treatment with sucralfate when alginate was supplemented for symptomatic control. Simon and Mueller [9] also compared the effect of sucralfate and ranitidine in reflux esophagitis. As in our study, the greater the degree of severity of re-
August 8,
1:
17
0.049 0.120
2
0.858 0.129
flux esophagitis, the lower were the chances of complete healing. Both forms of treatment, given in doses of 1 g sucralfate, four times daily, or ranitidine, 150 mg b.i.d., also gave similar results. Reflux esophagitis was healed in 14 of 22 patients treated with sucralfate and 13 of 19 when ranitidine was used for 8 weeks. The greater improvement in their study is explained by the larger number of patients in whom the esophagitis was in stage 1. Whether larger doses of either drug would have been more beneficial is also debatable. There are reports of better healing rates with each drug when patients are evaluated after 3 and 6 months of treatment [4]. As in the study reported by Koelz et aE [61, age, sex, duration of history, and alcohol consumption did not seem to affect the outcome in the two groups. An unfavorable effect in smokers was noted in the report of Koelz et al, but there was no difference in our two groups. Either drug proved to be safe, with few side effects. The default rates were believed to be due to a reluctance on the part of patients to undergo a second endoscopy at the conclusion of the trial. In conclusion, both ranitidine and sucralfate are safe drugs and appear to result in a significant improvement in reflux esophagitis. Both drugs also appear to be more effective in stages 1 and 2 reflux esophagitis, but gave disappointing results in more serious esophagitis. Because the drugs have different modes of action, and because both have similar effects, a combination therapy of the two drugs used for a longer period may prove to be more effective than each drug used separately. Although, as indicated, the findings with sucralfate and ranitidine in patients with reflux esophagitis completing the trial suggest a benefit of these agents, the absence of a placebo control group and the high default rates, particularly for those receiving sucralfate, preclude any firm conclusions as to relative or specific efficacy of these agents in this condition.
1991
The American Journal of Medicine
Volume 91 (suppl 2A)
2A421s
SYMPOSIUM ON SUCRALFATE / BREMNER ET AL
REFERENCES 1. Tytgat GNJ. Clinical efficacy of sucralfate in reflux esophagitis. Comparison with cimetidine Am J Med 1987; 83 (Suppl 38): 38-42. 2. Koelz HR. Treatment of reflux esophagitis with He blockers, antacids and prokinetic drugs. An analysis of randomized clinical trials. Stand J Gastroenterol 1989; 24 (suppl 156): 25-36. 3. Konturek SJ, Kwiecien N, Obtulowicz W, Kopp B, Olesky J. Double blind controlled study on the effect of sucralfate on gastric prostaglandin formation and microbleeding in normal and aspirin-treated man. Gut 1986; 27: 1450-6. 4. Meuwissen SGM, KlrnkenbergKnol EC. Treatment of reflux oesophagitis with Ha receptor antagonists. Stand J Gastroenterol 1988; 23 (Suppl 146): 201-13.
2HZ2S
August 8, 1991
The American Journal of Medicine
5. Bianchi PG, Pace F, Lazzaroni M Esophagitis healing with ranitidine. Gastroenterology 1987; 92: 2051-2. 6. Koelz HR, Birchler R, Bretholz A, et al. Healing and relapse of reflux esophagitis during treatment with ranitidine. Gastroenterology 1986; 91; 1198-205. 7. Willrams RM, Orlando RC, Bozymski EM, et al. Multicenter trial of sucralfate suspension for the treatment of reflux esophagitis. Am J Med 1987; 83 (Suppl 38): 61-6. 8. Weiss W, Brunner H, BiXtner GR, et al. Therapie deur refluxosophagitis sucralfat. Dtsch Med Wochenschr 1983; 108: 1706-11.
mit
9. Simon B, Mueller P. Comparison of the effect of sucralfate and ranitidine in reflux esophagitis. Am J Med 1987; 83 (Suppi 38): 43-7.
Volume 91 (suppl 2A)
