Octreotide for esophageal variceal bleeding treated with endoscopic sclerotherapy: a randomized, placebo-controlled trial. A multicenter, randomized, double-blind trial of somatostatin in the management of acute hemorrhage from esophageal varices. Somatostatin treatment and risk stratification by continuous portal pressure monitoring during acute variceal bleeding. Sclerotherapy with or without octreotide for acute variceal bleeding. Sclerotherapy plus octreotide versus sclerotherapy alone in the management of gastro-oesophageal variceal hemorrhage. Early administration of vapreotide for variceal bleeding in patients with cirrhosis. Randomized, double-blind, placebo-controlled trial of somatostatin for variceal bleeding. Emergency control and prevention of early variceal rebleeding. [Terlipressin and somatostatin in the treatment of hemorrhages from rupture of esophageal varices]. Early administration of somatostatin and efficacy of sclerotherapy in acute oesophageal variceal bleeds: the European Acute Bleeding Oesophageal Variceal Episodes (ABOVE) randomised trial. Comparison of endoscopic variceal sclerotherapy alone and in combination with octreotide in controlling acute variceal hemorrhage and early rebleeding in patients with low-risk cirrhosis. Octreotide in acute bleeding esophageal varices: a prospective randomized study. Prospective randomised study of effect of octreotide on rebleeding from oesophageal varices after endoscopic ligation.
Endoscopic sclerotherapy is considered a first line therapy to stop bleeding from esophageal varices, but acute variceal bleeding is still associated with high risk of rebleeding and death. We compared the use of octreotide with endoscopic sclerotherapy versus sclerotherapy alone to control acute variceal bleeding and prevent rebleeding in patients with cirrhosis.
                In a prospective controlled trial, 68 patients with cirrhosis and acute variceal bleeding who underwent emergency sclerotherapy were randomly assigned to receive a continuous infusion of octreotide or placebo for two days. The primary outcome measure was 7-day mortality.
                After seven days the overall mortality was 19.1%, and the proportion of patients who died in octreotide group (8 of 40, or 20%) was similar to the placebo group (5 of 28, or 17.85%; p = 0.74). Rebleeding occurred in 20.6% (14 of 68 patients), being 20% (8 of 40) in the octreotide group vs. 21.4% (6 of 28) in the placebo group (p = 0.88). The mean number of units of blood transfused after sclerotherapy was 2.05 units in the octreotide group vs. 2.08 units in the placebo group (p = 0.96). Thirty patients needed intensive care support (20 of 40 in the octreotide group vs. 10 of 28 in the placebo group; p = 0.24). The differences remained without statistical significance even after adjustment for hepatic function and endoscopic bleeding stigmata by a linear regression model analysis test.
                In patients with cirrhosis, octreotide intravenous per 48h associated with sclerotherapy is not superior to sclerotherapy alone in terms of 7-day mortality, frequency of rebleeding, number of units of packet red blood cell transfusion and length of stay in intensive care setting. A prospective, randomized, placebo-controlled, double-blind, multicenter clinical trial of intravenous somatostatin (Stilamin; Serono Laboratories, Inc., Randolph, MA) was performed in 102 patients with actively bleeding esophageal varices from August, 1985, to November, 1986. Patients had major hemorrhage indicated by hematemesis or melena and evidence of significant blood loss. For entry, patients had to have endoscopic demonstration of active bleeding from esophageal varices or stigmata of recent hemorrhage and bright red blood in the gastric aspirate with no other source of bleeding found. Randomized patients received identical-appearing somatostatin or placebo for a 30-hr study period. Those given somatostatin received a 250-micrograms bolus and a 250-micrograms per hr infusion with repeat bolus and doubling of the infusion if the bleeding was not controlled. In retrospect, 18 patients could not be evaluated. Of the 84 evaluable patients, 48 received somatostatin and 36 placebo. They were comparable in age, gender, severity of liver disease and history of variceal bleeding. Transfusion requirements were similar in both groups. Bleeding stopped for 12 consecutive hr during 30 hr of the study period in 31 (65%) of the somatostatin group vs. 30 (83%) of the placebo group (p = 0.06). The median time to cessation of bleeding was 2 hr in the placebo group and 3 hr in the somatostatin group. Deaths following the study period were nine (25%) in the placebo group and 15 (31%) in the somatostatin group. Within the limitations of the present study, we conclude that somatostatin was ineffective in the management of active bleeding of esophageal varices. During acute variceal bleeding, several factors may lead to elevations of hepatic venous pressure gradient (HVPG), which may precipitate further hemorrhage. Whether somatostatin can suppress these increments is unknown. This study monitored somatostatin effects on HVPG during acute bleeding and assessed whether the changes affect outcome.
                In 40 patients with acute variceal bleeding treated with sclerotherapy, a catheter was placed into a main hepatic vein for 24-hour serial measurements of HVPG. After baseline measurements, patients received somatostatin (N = 25) or placebo (N = 15) under double blind conditions.
                Somatostatin but not placebo produced a sustained decrease in HVPG (from 20.7 +/- 3.7 mm Hg to 17.7 +/- 2.7, P < 0.01). In patients receiving placebo, HVPG increased after a test meal (P = 0.018) and after blood transfusion (P = 0.034). Somatostatin completely prevented these increments. HVPG decreased significantly only in patients without further bleeding. One of 27 patients with HVPG <20 mm Hg at baseline or decreased >10% rebled vs. 9 of 13 who had neither of these 2 criteria (P < 0.0001). Both criteria had independent prognostic value for further bleeding.
                During acute variceal bleeding, somatostatin produces a significant and sustained decrease in HVPG and prevents secondary elevations. Monitoring HVPG may stratify further bleeding risk and discriminate treatment response. Sclerotherapy is considered the most effective way to stop bleeding from esophageal varices, but acute variceal bleeding is still associated with a high risk of rebleeding and death. We compared sclerotherapy alone with sclerotherapy and octreotide to control acute variceal bleeding and prevent early rebleeding in patients with cirrhosis.
                In a double-blind, prospective trial, 199 patients with cirrhosis and acute variceal bleeding who underwent emergency sclerotherapy were randomly assigned to receive a continuous infusion of octreotide (25 micrograms per hour) or placebo for five days. The primary outcome measure was survival without rebleeding five days after sclerotherapy.
                After five days, the proportion of patients who had survived without rebleeding was higher in the octreotide group (85 of 98 patients, or 87 percent) than in the placebo group (72 of 101, or 71 percent; 95 percent confidence interval for the difference, 4 to 27 percent; P = 0.009). The mean number of units of blood transfused within the first 24 hours after sclerotherapy was lower in the octreotide group (1.2 units; range, 0 to 7) than in the placebo group (2.0 units; range, 0 to 10; P = 0.006). A logistic-regression analysis showed that the treatment assignment (P = 0.003) and the number of blood units transfused before any other treatment was undertaken (P = 0.002) were the only two variables independently associated with survival without rebleeding. After adjustment for base-line differences between the two groups, the odds ratio for treatment failure in the placebo group, as compared with the octreotide group, was 3.3 (95 percent confidence interval, 1.5 to 7.3). The mean (+/- SD) 15-day cumulative survival rate (estimated by the Kaplan-Meier method) was 88 +/- 12 percent in both groups. Side effects were minor, and their incidence was similar in the two groups.
                In patients with cirrhosis, the combination of sclerotherapy and octreotide is more effective than sclerotherapy alone in controlling acute variceal bleeding, but there is no difference between the overall mortality rates associated with the two approaches to treatment. There are different ways for controlling oesophageal variceal bleed which include pharmacological and endoscopic methods. In this study we compare efficacy of octreotide (50 g/hr for 48 hours) combined with sclerotherapy versus sclerotherapy alone in patients with acute bleeding from gastro-oesophageal varices (GOV).
                It was a randomized clinical controlled trial conducted at Aga Khan University Hospital, Karachi, from January 1997 to December 1998. We evaluated the role of octreotide (50 g/hr for 48 hours) combined with sclerotherapy versus sclerotherapy alone in a total of 105 adult cirrhotic patients who had acute bleeding from GOV. Patients were assigned to receive octreotide plus sclerotherapy or sclerotherapy alone. Primary outcome measure was 5-day survival without rebleeding. The hospital stay in days and blood transfusion requirements were also compared in the combined treatment group versus sclerotherapy alone group.
                Initial control of bleeding was achieved in 46/51 (90.2%) patients who received combined treatment compared to 41/54 (75.9%) patients (p = 0.05) in sclerotherapy alone group. Rebleeding after the first 48 hours was less in the octreotide treated patients 2/46 vs. 8/41 patients (p = 0.003). The octreotide treated patients had a better short term (5 days) survival without rebleeding 44/51 vs. 33/54 (p = 0.003) and shorter hospital stay, 5.31 +/- 3.87 days vs. 6.63 +/- 3.86 (p = 0.008) as compared to sclerotherapy alone group. The blood transfusion requirement was also less in the combined treatment group 3.88 +/- 2.80 vs. 5.37 +/- 3.15 units (p = 0.002).
                1) The combination of sclerotherapy, and octreotide infusion over 48 hours is more effective than sclerotherapy alone in the treatment of acute variceal bleeding and prevention of early rebleed in cirrhotic patients. 2) It leads to shorter hospital stay and 3) less blood transfusion requirements. 4) Although early survival without rebleeding is improved, the overall mortality at the end of hospitalization period is similar in the two groups of treated patients. In patients with cirrhosis, pharmacologic or endoscopic treatment may control variceal bleeding. However, the effects of early administration of a somatostatin analogue followed by endoscopic treatment are unknown.
                We studied the effects of treatment with vapreotide, a somatostatin analogue, begun before endoscopic treatment in 227 patients with cirrhosis who were hospitalized for acute upper gastrointestinal bleeding. The patients were randomly assigned to receive vapreotide (a 50-microg intravenous bolus followed by an infusion at a rate of 50 microg per hour for five days) or placebo within a mean (+/-SD) of 2.3+/-1.5 hours after admission. All the patients received endoscopic treatment a mean of 2.6+/-3.3 hours after the infusion was begun. After the exclusion of 31 patients whose bleeding was not caused by portal hypertension, there were 98 patients in each group.
                At the time of endoscopy, active bleeding was evident in 28 of 91 patients in the vapreotide group (31 percent), as compared with 43 of 93 patients in the placebo group (46 percent) (P=0.03). During the five-day infusion, the primary objective--survival and control of bleeding--was achieved in 65 of 98 patients in the vapreotide group (66 percent) as compared with 49 of 98 patients in the placebo group (50 percent) (P=0.02). The patients in the vapreotide group received significantly fewer blood transfusions (2.0+/-2.2 vs. 2.8+/-2.8 units, P=0.04). Overall mortality rates at 42 days were not significantly different in the two groups.
                In patients with cirrhosis and variceal bleeding, the combination of vapreotide and endoscopic treatment is more effective than endoscopic treatment alone as a method of controlling acute bleeding. However, the use of combination therapy does not affect mortality rates at 42 days. A randomized, double-blind, placebo-controlled trial of somatostatin was conducted among 120 patients admitted for bleeding esophageal varices (59 placebo, 61 somatostatin). An initial 250-micrograms bolus of somatostatin followed by a 5-day continuous infusion of 250 micrograms/h and an identical administration of placebo were evaluated for both the control of bleeding and prevention of early rebleeding from varices. Failure to control bleeding occurred in 22 (36%) somatostatin patients vs. 35 (59%) placebo patients, with time to failure occurring earlier with placebo (P = 0.036). blood and plasma transfused per hour during drug infusion of trial drug was reduced in the somatostatin group: median 0.033 vs. 0.105 unit/h (P = 0.025). Use of balloon tamponade was halved in somatostatin-treated patients. The average effect of somatostatin was a 41% reduction in the hazard of failure (95% confidence interval, -1% to 65%, P = 0.0545) after adjustment for the severity of liver disease, which was the only other variable having a significant influence on time to failure. There was no difference in 30-day mortality per admission (7 placebo, 9 somatostatin) or complications. It is concluded that somatostatin is safe and more effective than placebo for the control of variceal bleeding. nan Sclerotherapy is widely used for acute variceal bleeding, although in emergencies bleeding makes it difficult to obtain the clear view required for safe and effective treatment. We investigated whether early administration of somatostatin would improve the efficacy of sclerotherapy.
                In this double-blind, prospective trial, patients who had cirrhosis with upper-gastrointestinal bleeding were randomly assigned natural somatostatin (6 mg per 24 h) or placebo for 120 h. In addition, intravenous bolus doses of somatostatin (250 micrograms) or placebo were injected after the start of the infusion, before emergency endoscopy or sclerotherapy, and when active bleeding was observed. The primary endpoint was treatment failure, defined as the occurrence during the infusion period of at least one of: excess transfusion of blood products, haematemesis, haemodynamic instability, need for rescue therapy, or death.
                205 patients were enrolled: 101 received somatostatin and 104 received placebo. Treatment failed in 35 somatostatin and 57 placebo recipients (p = 0.004); death or use of rescue therapy occurred in nine and 19 patients, respectively (p = 0.05). The mean quantity of blood products transfused over 120 h (adjusted for baseline haemoglobin) was 2.64 (SD 0.35) units in the somatostatin group versus 3.62 (0.35) units in the placebo group (p = 0.05). At endoscopy, active bleeding from oesophageal varices was less frequent (27 vs 42 patients, p = 0.012) and the sclerotherapy procedure was easier (2.8 vs 4.7 cm, p = 0.0027) in the somatostatin than in the placebo group.
                Early administration of natural somatostatin continued for 120 h, combined with additional bolus injections, is more effective than placebo in the overall control of acute variceal haemorrhage in patients with cirrhosis undergoing sclerotherapy. Efficacy of endoscopic variceal sclerotherapy (EVS) alone and in combination with octreotide in controlling acute variceal bleeding and preventing early rebleeding was compared in a double-blind study.
                Consecutive patients presenting with variceal bleeding with low-risk liver cirrhosis were randomized into two groups. Group A received EVS with 3-5 ml of ethanolamine oleate per varix and placebo injection at 50 microg/h; group B received the combined therapy of EVS and octreotide 50 microg/h continuously for 5 days. A total of 70 patients (mean age, 38.4 +/- 8.6 yr) were selected for the study, which included 56 men (mean age, 37.9 +/- 8.5 yr) and 14 women (mean age, 40.6 +/- 9.0 yr). Thirty-five patients were allocated in each group.
                In group A bleeding was controlled in 30 patients (85.7%) and in group B in 33 (94.3%) (p = 0.24). The number of patients who rebled during the first 5 days after sclerotherapy was eight (22.9%) and two (5.7%) in groups A and B, respectively (p = 0.04). The mean packs of blood transfused to the patients of groups A and B were 2.1 +/- 1.2 packs and 1.5 +/- 0.7 packs, respectively (p = 0.03). The mean hospital stay of group A was 6.6 +/- 1.3 days, whereas that in group B was 5.9 +/- 1.2 days (p = 0.04). One patient from each group died during the course of the study.
                No significant difference was observed in arrest of bleeding in the two groups, but episodes of early rebleeding, blood transfusions, and hospital stay was significantly less in group B. To assess the value of octreotide in the control of acute bleeding esophageal varices, in a prospective randomized study.
                One hundred and ninety-seven patients admitted for variceal bleeding confirmed at endoscopy were recruited and divided into two groups: group I (n = 111) with endoscopic stigmata of recent bleeding; and group II (n = 86) with active bleeding at emergency endoscopy. Patients in group I were randomized to receive a continuous infusion of octreotide (n = 58) or emergency sclerotherapy (n = 53). Patients in group II were assigned to sclerotherapy (n = 42) or to sclerotherapy plus octreotide (n = 44). At the end of the period of study (48 hours), patients were submitted to sclerotherapy or band ligation until variceal obliteration was achieved.
                In group I, octreotide was found to be as effective as sclerotherapy regarding hemostasis at 48 hours and on day 7 after the index bleeding episode. Transfusion needs were not significantly different for the two treatment modalities. In group II, the association of octreotide with sclerotherapy was significantly better than sclerotherapy alone either in controlling acute active bleeding (P < 0.001) or in achieving hemostasis at 48 hours (P < 0.01). Transfusion needs were significantly fewer in patients treated with this therapeutic association as compared to sclerotherapy alone.
                These results suggest that octreotide infusion is effective in the treatment of variceal bleeding. In patients with recent bleeding, octreotide infusion is as effective as emergency sclerotherapy. In active variceal bleeding, it is a valuable adjuvant treatment in association with emergency sclerotherapy. Up to a third of patients have early rebleeding from oesophageal varices after endoscopic variceal ligation. Octreotide infusion is effective for control of variceal bleeding. We investigated the efficacy of octreotide infusion as an adjunct to endoscopic variceal ligation to prevent early rebleeding from varices. 100 consecutive patients admitted with endoscopically confirmed oesophageal varices and active bleeding or signs of recent haemorrhage were randomly assigned endoscopic variceal ligation alone or octreotide (50 micrograms intravenous bolus injection followed by intravenous infusion at 50 micrograms per h for 5 days) plus endoscopic variceal ligation. Three patients in each group were excluded. Bleeding was controlled in 44 of 47 patients who received variceal ligation alone and in 45 of 47 who received combined treatment (p = 1.0). Recurrent bleeding was documented in 18 (38% [24-52]) patients who received variceal ligation alone and in four (9% [3-21] who received combined treatment (p = 0.0007). The relative risk of rebleeding was lower (0.22 [0.08-0.60]) in the combined therapy group. Ten patients in the variceal ligation group and one in the combined therapy group required balloon tamponade for massive haematesis and haemodynamic instability (p = 0.0039). The in-hospital and 30-day mortality rates were higher in the variceal ligation group than in the combined therapy group (19 vs 9% and 23 vs 11%), but the differences did not reach significance. The relative risks of in-hospital (0.5 [0.04=5.3]) and 30-day (0.45 [0.17-1.2]) mortality were lower in the combined therapy group. Octreotide significantly reduces recurrent bleeding and the need for balloon tamponade in patients with variceal haemorrhage treated by endoscopic variceal ligation.
The need for blood transfusions corresponded to one half unit of blood saved per patient. It is doubtful whether this effect is worthwhile. The findings do not suggest a need for further placebo-controlled trials of the type reviewed here. A large placebo controlled trial enrolling thousands of patients is needed if one wishes to rule out the possibility that a worthwhile effect on mortality might have been overlooked.