Terlipressin in bleeding esophageal varices: a placebo-controlled, double-blind study. Double-blind randomized controlled trial comparing terlipressin and somatostatin for acute variceal hemorrhage. Variceal Bleeding Study Group. Multicenter randomized controlled trial of terlipressin versus sclerotherapy in the treatment of acute variceal bleeding: the TEST study. Placebo-controlled trial of terlipressin (glypressin) in the management of acute variceal bleeding. A randomized trial of terlipressin plus nitroglycerin vs. balloon tamponade in the control of acute variceal hemorrhage. Treatment of active gastroesophageal variceal bleeding with terlipressin or hemostatic balloon in patients with cirrhosis. A randomized controlled trial. Terlipressin or vasopressin plus transdermal nitroglycerin in a treatment strategy for digestive bleeding in cirrhosis. A randomized clinical trial. Liver Study Group of V. Cervello Hospital. Terlipressin (triglycyl-lysine vasopressin) controls acute bleeding oesophageal varices. A double-blind, randomized, placebo-controlled trial. Terlipressin (glypressin) versus somatostatin in the treatment of bleeding esophageal varices--final report of a placebo-controlled, double-blind study. Terlipressin plus transdermal nitroglycerin vs. octreotide in the control of acute bleeding from esophageal varices: a multicenter randomized trial. Early administration of terlipressin plus glyceryl trinitrate to control active upper gastrointestinal bleeding in cirrhotic patients. A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Controlled trial of terlipressin ('Glypressin') versus vasopressin in the early treatment of oesophageal varices. Terlipressin as a rescue therapy for catecholamine-resistant septic shock in children. Octreotide versus terlypressin in acute variceal hemorrhage in liver cirrhosis. Emergency control and prevention of early rebleeding.
The effect of terlipressin (N-alpha-triglycyl-8-lysine-vasopressin) in bleeding esophageal varices was evaluated in a prospective placebo-controlled study. Fifty bleeding episodes from esophageal varices in 34 patients were randomized. Standard therapy with transfusions, fluid and electrolyte correction, and lactulose was performed in both groups. Balloon tamponade was used in 20 bleeding episodes in the terlipressin group and in 19 bleeding episodes in the control group. In the terlipressin group, hemorrhage was controlled in all bleeding episodes (25/25) whereas in the placebo group, only 20 of 25 bleeding episodes could be stopped within 36 hr (p less than 0.05). Sclerotherapy was performed in five bleeding episodes in the terlipressin group and in seven bleeding episodes in the placebo group. Treatment failures, including patients who required sclerotherapy, occurred in five bleedings in the terlipressin group and in 12 in the control group (p less than 0.05). The hospital mortality rate was 12% (3/25) in the terlipressin group and 32% (8/25) in the control group. Patients in the terlipressin group required fewer transfusions, the balloon needed to be inflated for a shorter time and the duration of bleeding was shorter than in the control group. However, these differences were not significant. These data do not allow conclusions concerning monotherapy with terlipressin, but they indicate that the addition of terlipressin to standard therapy may increase the control rate in acute variceal hemorrhage. Terlipressin and somatostatin decrease portal pressure and have been used to treat variceal hemorrhage, but they have not been adequately compared. The aim of this study was to compare the efficacy and safety of these drugs in the treatment of variceal bleeding in cirrhotic patients.
                Of 161 patients with variceal bleeding. 80 were randomized to receive (double-blind) intravenous terlipressin (2 mg/4 h) and 81 to receive somatostatin (continuous infusion of 250 micrograms/h after an intravenous injection of 250 micrograms). Success of therapy was defined as a 24-hour bleeding-free period within 48 hours from randomization.
                Success of therapy was similar with terlipressin (80%) and somatostatin (84%). In patients with Child's class A and B disease, terlipressin was effective in 52 of 60 (87%) and somatostatin in 48 of 55 (87%). Success rates in class C were 60% and 77% (P = 0.33). No differences were observed in rebleeding rates (30% vs. 28.4%) and 6-week mortality rates (13 vs. 13 patients). Incidence of side effects was significantly higher in the terlipressin group (38.8% vs. 23.5%; P = 0.042). Severe side effects requiring intervention occurred in 5 of 80 and 4 of 81 patients, respectively.
                Terlipressin and somatostatin are highly effective as first-line treatment of variceal hemorrhage in cirrhotic patients. The low incidence of severe side effects suggests that drug therapy may be maintained for longer periods to prevent early rebleeding. Failure to control bleeding and early rebleeding account for the high mortality associated with variceal hemorrhage in cirrhosis. We compared endoscopic sclerotherapy to terlipressin, a drug that effectively controls acute bleeding while reducing in-hospital mortality. This multicenter randomized controlled trial included 219 cirrhotic patients admitted for endoscopy-proven acute variceal bleeding and randomized to receive repeated injections of terlipressin during 6 days (n = 105) or emergency sclerotherapy (n = 114). Success was defined as obtaining control of bleeding (24-hour bleeding-free period during the first 48 hours) and lack of early rebleeding (any further bleeding from initial control to 5 days later) and survival during the study. Both groups were similar at inclusion. Failure rate for terlipressin was 33% and 32% for sclerotherapy (not significant [NS]). Early rebleeding was responsible for 43% and 44% of failures, respectively. This high efficacy was observed in both Child-Pugh class A + B and Child-Pugh class C patients. Both treatments were similar regarding transfusion requirements, in-hospital stay, and 6-week mortality (26 vs. 19 patients). Side effects appeared in 20% of patients receiving terlipressin and in 30% of those on sclerotherapy (P =.06); being serious in 4% and 7%, respectively (NS). In conclusion, terlipressin and sclerotherapy are equally highly effective therapies achieving the initial control of variceal bleeding and preventing early rebleeding. Both treatments are safe, but terlipressin is better tolerated. Therefore, terlipressin may represent a first-line treatment in acute variceal bleeding until the administration of elective therapy, especially in hospitals where a skilled endoscopist is not available 24 hours a day. In a double-blind trial 60% of acute variceal bleeding episodes were controlled with terlipressin (glypressin) compared with 37% in patients given placebo (NS). Rebleeding was more common in the placebo group so that at 5 days bleeding remained under control in 54% of patients treated with terlipressin compared with only 19% after placebo therapy (p less than 0.025). Blood transfusion requirements were similar in the two groups. Terlipressin appeared to be the most effective in those patients with severe hepatic dysfunction. A randomized trial was undertaken to determine the efficacy of nitroglycerin in addition to terlipressin infusion to improve the control of acute variceal hemorrhage compared with balloon tamponade. Forty-seven bleeding episodes in 34 cirrhotic patients were included, with terlipressin plus sublingual nitroglycerin in 23 episodes (group I) and balloon tamponade in 24 episodes (group II). At the end of the 12-hr period, hemorrhage had been equally controlled in both groups (18 of 23; 78% in group I and 19 of 24; 79% in group II). When attempted, balloon tamponade appeared more efficient in the failures of group I (4 of 4) than did terlipressin plus nitroglycerin in the failures of group II (0 of 3), although this difference was not significant. Major complications were rare (one in each group) and never required cessation of therapy. Thus terlipressin and nitroglycerin were as effective as balloon tamponade in controlling variceal hemorrhage and were associated with few minor complications. Gastroesophageal variceal bleeding due to portal hypertension should be treated by endoscopic sclerotherapy. This procedure, however, has some limitations. It has been established that vasoactive drugs are effective for controlling active variceal bleeding. We report the results of a randomized controlled trial comparing terlipressin to hemostatic tube (Linton-Michel tube) for the treatment of bleeding gastroesophageal varices in cirrhotic patients. Thirty-seven cirrhotic patients with a total of 40 episodes of gastroesophageal variceal bleeding were included in this trial. Patients were randomly assigned to intravenous terlipressin or Linton-Michel tube (LM tube), for 24 h. During this period, hemostasis was defined as obtaining of hemodynamic and hematocrit stabilization and/or absence of hematemesis or melena. Bleeding recurrence was assessed during a 1-month period after treatment. Twenty bleeding episodes were treated with terlipressin (Group I) and 20 with LM tube (Group II). Both groups of patients were similar in age, sex distribution, etiology of cirrhosis and degree of hepatic insufficiency. Bleeding was controlled in 70% of patients from Group I and in 95% from Group II (p < 0.05) during treatment. Bleeding recurred in 14% of patients in Group I vs. 36% in Group II 1 week following the treatment (p > 0.05) and in 16.6% in Group I vs. 83.3% in Group II 1 month after treatment (p < 0.05). Complications were more frequent in Group II than in Group I (65 vs. 15%, p < 0.05). Mortality rate was similar in both groups 1 month after treatment. In conclusion, hemostatic tubes were superior to terlipressin for the control of active gastroesophageal variceal bleeding within the first 24 h. Complications and bleeding recurrence were more frequent in patients treated by hemostatic tube within a period of 1 month after treatment. Mortality rate was similar in both groups of patients. Between 1988 and 1990 an unblinded, randomized trial of terlipressin or vasopressin plus transdermal nitroglycerin, as part of a treatment strategy including emergency sclerotherapy for actively bleeding varices, was conducted during 165 admissions in 137 patients with cirrhosis and upper digestive bleeding. Eighty-four patient admissions were assigned to terlipressin (2 mg every 6 h) and 81 to vasopressin (0.4 to 0.8 unit per min) plus transdermal nitroglycerin (20 to 80 mg). The two groups were comparable for relevant clinical data, but there were slightly more patients with hepatocellular carcinoma or terminal conditions in the terlipressin group. After the 24-h study period, failure to control bleeding was 20/84 (25%) in the vasopressin and 14/81 (17%) in the terlipressin group (p = 0.19). Corresponding figures for patients bleeding from varices (emergency sclerotherapy in 43 and 45, respectively) were 13/55 (24%) and 5/56 (9%; p = 0.035), from other sources 5/16 (31%) and 2/15 (13%; p = 0.23), from undefined sources 2/10 (20%) and 7/13 (54%; p = 0.1). In a logistic multivariate regression model the odds ratio for terlipressin adjusted for prognostic factors was 0.45 (p = 0.07). There were seven major side effects requiring treatment discontinuation in the vasopressin and one in the terlipressin group. These results suggest that terlipressin alone is as effective as vasopressin plus transdermal nitroglycerin, with less severe side effects, in 24-h control of upper gastrointestinal bleeding in patients with cirrhosis. The haemostatic effect of terlipressin (triglycyl-lysine vasopressin; Glypressin) on bleeding from oesophageal varices was evaluated in a placebo-controlled, double-blind, randomized clinical trial. Patients with clinically suspected liver cirrhosis were included in the study if they had been admitted to hospital with an extensive haemorrhage within the last 24h before diagnostic endoscopy. The patients randomized after stratification for severity of liver disease. Terlipressin or placebo was administered as intravenous bolus injections every 4th h during a period of 24 to 36 h or until the clinical course necessitated active intervention (failure or withdrawal). Sixty patients entered the study; 31 patients were allocated to receive terlipressin, and 29 patients to receive placebo. Bleeding from varices was arrested in 28 of the 31 receiving terlipressin, as compared with 17 of the 29 receiving placebo (p less than 0.01). Patients receiving active drug required significantly fewer blood transfusions (p less than 0.05). Most of the side effects were classified as mild and were registered in the terlipressin group. One hundred and six episodes of bleeding from esophageal or gastric varices in 72 patients with cirrhosis of the liver were randomized to treatment either with intravenous terlipressin 2 mg initially and 1 mg every four hours for 24 hours together with bolus injection and continuous infusion of placebo, or with somatostatin 250 micrograms as a bolus and continuous infusion of 250 micrograms/h somatostatin for 24 hours and placebo injections. Standard treatment with transfusions, fluid and electrolyte correction, and lactulose was administered in both groups. In the terlipressin group, 48 out of 53 bleeding episodes (91%) and in the somatostatin group 43 out of 53 bleeds (81%) were initially stopped by the vasoactive drugs. Four of the five bleeds not arrested by terlipressin, and nine of the ten bleeds not arrested by somatostatin, were stopped by balloon tamponade. In one patient in each group variceal bleeding could not be stopped initially, and both patients died. The failure rate of the vasoactive treatment alone, including rebleeds within the study period, was 17% in the terlipressin, and 28% in the somatostatin, group. The initial hemostasis, including balloon tamponade, were 98%, and the definitive bleeding control rates were 89% in both groups. The hospital mortality rate was 21% (11/53) in the terlipressin, and 21% (11/53) in the somatostatin, group. Blood transfusions and duration of bleeding did not differ significantly. The study indicates that a large proportion of bleeds from esophageal and fundic varices can be stopped initially (86%) and definitively controlled (77%) by vasoactive drugs alone. We undertook a multicenter randomized trial to compare the efficacy of terlipressin combined with transdermal nitroglycerin and that of octreotide in the emergency control of acute variceal hemorrhage in cirrhosis. Over 16 mo, 87 patients with endoscopically proved active bleeding from esophageal or cardiac varices were enrolled in five centers in France and randomly assigned to receive intravenous terlipressin (2 mg and then 1 mg/4 hr over 24 hr) and transdermal nitroglycerin (10 mg/12 hr over 24 hr) (group 1) or octreotide (continuous intravenous infusion of 25 micrograms/hr over 12 hr and then 100 micrograms at hr 12 and hr 18 subcutaneously) (group 2). Initial control of bleeding was assessed at the end of 12 hr of treatment on the basis of stability of blood pressure and hematocrit level with no further transfusion requirements. At 12 hr, bleeding was controlled in 59% (24 of 41) in group 1 and 78% (36/46) of group 2 patients (Fisher's exact test, p = 0.064). Mean transfusion requirements over this 12-hr period were significantly greater in group 1 (three blood units; range = 0 to 13) than in group 2 (one blood unit; range = 0 to 5) (p = 0.002). After the first 12 hr, 20% of patients (5 of 24) had repeat bleeding in group 1 compared with 27% (10 of 36) in group 2. During the first 48-hr period, five patients (12%) died in group 1, compared with 3 (6%) in group 2. Few side effects were noted in either group. However, in group 1 two patients experienced severe bradycardia; it resulted in death in one patient.(ABSTRACT TRUNCATED AT 250 WORDS) Upper gastrointestinal bleeding (GIB) is a major complication in cirrhotic patients. Endoscopy and oesophageal sclerosis are reference treatments and must be done as soon as possible. However, such treatment is not possible unless the patient is admitted to hospital. In a prospective, randomised, double-blind trial, we compared the efficacy of terlipressin combined with glyceryl trinitrate (TER-GTN), administered as early as possible to 76 patients with cirrhosis who had active GIB (84 bleeding episodes). Infusion was done at the patient's home by the physician on the emergency team (a mobile intensive care unit) if the patient had GIB and a history and clinical signs of cirrhosis. Patients received either an intravenous injection (1 to 2 mg) of TER-GTN or a double-placebo injection, and then another injection at 4 and 8 h. Control of bleeding, rebleeding, and mortality rate at days 15 and 42 were evaluated. In most patients, endoscopy confirmed the rupture of oesophageal varices (75.7%). Bleeding control was significantly better in the TER-GTN group (n = 41) than in the double-placebo group (n = 43) (p = 0.034). Mortality due to bleeding episodes was significantly lower in the TER-GTN group than in the double-placebo group at day 15 (p = 0.035) and at day 42 (p = 0.06). There were no serious side-effects. Early administration of TER-GTN lowers the deleterious consequences of prolonged hypovolaemia on the hepatic function of these patients. Hepatorenal syndrome (HRS) type 1 is a progressive functional renal failure in subjects with advanced liver disease. The aim of this study was to evaluate the efficacy and safety of terlipressin, a systemic arterial vasoconstrictor, for cirrhosis type 1 HRS.
                A prospective, randomized, double-blind, placebo-controlled clinical trial of terlipressin was performed. Subjects with type 1 HRS were randomized to terlipressin (1 mg intravenously every 6 hours) or placebo plus albumin in both groups. The dose was doubled on day 4 if the serum creatinine (SCr) level did not decrease by 30% of baseline. Treatment was continued to day 14 unless treatment success, death, dialysis, or transplantation occurred. Treatment success was defined by a decrease in SCr level to </=1.5 mg/dL for at least 48 hours by day 14 without dialysis, death, or relapse of HRS type 1.
                Fifty-six subjects were randomized to each arm. Treatment success with terlipressin was double that with placebo (25% vs 12.5%, P = .093). SCr level improved from baseline to day 14 on terlipressin (-0.7 mg/dL) as compared with placebo (0 mg/dL), P < .009. Terlipressin was superior to placebo for HRS reversal (34% vs 13%, P = .008), defined by decrease in SCr level </=1.5 mg/dL. Overall and transplantation-free survival was similar between study groups; HRS reversal significantly improved survival at day 180. One nonfatal myocardial infarction occurred with terlipressin, but the total adverse event rate was similar to placebo.
                Terlipressin is an effective treatment to improve renal function in HRS type 1. In a randomised controlled trial the effect of intermittent bolus injection of triglycyl lysine vasopressin (terlipressin 'Glypressin') (2 mg that 6-hourly), an analogue of vasopressin, was compared with that of a constant peripheral intravenous infusion of vasopressin (0.4 units/Min) in the initial management of bleeding oesophageal varices in nineteen patients. Failure of vasopressin therapy was defined as continued bleeding of sufficient severity to necessitate the passage of a Sengstaken tube. Bleeding was controlled in 70% of patients treated with glypressin but in only 9% of patients given vasopressin. The glypressin group required significantly less blood after randomisation than the vasopressin group. Because of its efficacy, lack of side-effects, and ease of administration, glypressin appears to be valuable in the management of bleeding varices. To evaluate the effect of terlipressin on oxygenation, PaO2/FIO2, heart rate, mean arterial pressure, and mortality in children with septic shock refractory to high doses of dopamine/dobutamine and adrenaline.
                A randomized, nonblind study in the pediatric intensive care unit of a university hospital.
                We studied 58 children with septic shock and refractory hypotension despite fluid loading and high doses of catecholamines, randomly enrolled to terlipressin (TP, n=30) or control (n=28). TP was administered as intravenous bolus doses of 20 microg/kg every 6 h for a maximum of 96 h. Hemodynamic changes, PaO2/FIO2 rates, length of stay, and mortality rate in PICU were recorded prospectively.
                Mean arterial pressure and PaO2/FIO2 significantly increased, and heart rate significantly decreased 30 min after each TP treatment, but mortality did not differ from control (67.3% vs. 71.4%). Mean stay in the PICU was shorter in the TP group (13.4+/-7.9 vs. 20.2+/-9.7 days and was longer among nonsurvivors of the TP group vs. control (10.4+/-6.9 vs. 6.2+/-3.4 days). Blood urea nitrogen, creatinine, AST, ALT, and urine output of patients in the TP group did not change after terlipressin.
                Although terlipressin infusion had no effect on mortality, it significantly increases mean arterial pressure, PaO2/FIO2, and survival time in nonsurvivors. Terlipressin seems to cause no adverse effect but warrants further evaluation as a rescue therapy in refractory septic shock. Sixty patients with endoscopically confirmed active variceal bleeding entered a randomized controlled clinical trial aimed at comparing the efficacy of octreotide vs. terlypressin in the control of acute variceal hemorrhage (period I, 24 h) and in the prevention of early rebleeding (period II, 6 days). Of the sixty 30 received octreotide (period I, 100 micrograms bolus followed by continuous intravenous infusion at 25 micrograms/h; period II, 100 micrograms t.i.d. subcutaneously), and 30 received terlypressin (period I, 2 mg intravenous bolus every 4 h; period II, 2nd day, 2 mg every 6 h; from 3th to 7th days, 1 mg every 6 h). Control of bleeding was achieved in 23 (76.6%) patients receiving octreotide and in 16 (53%) treated with terlypressin (NS); none of these patients suffered rebleeding during treatment. No significant difference in mortality was observed between the two groups during the hospitalization period. Complications due to therapy were lower with octreotide than with terlypressin (P < 0.01). Under the same effectiveness conditions the cost/benefit ratio must be taken into account.
On the basis of a 34% relative risk reduction in mortality, terlipressin should be considered to be effective in the treatment of acute variceal hemorrhage. Further, since no other vasoactive agent has been shown to reduce mortality in single studies or meta-analyses, terlipressin might be the vasoactive agent of choice in acute variceal bleeding.