Terlipressin in Bleeding Esophageal Varices: A Placebo–Controlled, Double–Blind Study

Abstract

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.

Multicenter Randomized Controlled Trial of Terlipressin Versus Sclerotherapy in the Treatment of Acute Variceal Bleeding: The TEST Study

“…5 This has encouraged the search for pharmacologic alternatives overcoming these limitations. Recent large randomized controlled trials (RCTs) showed that terlipressin effectively controls variceal bleeding with a low rate of side-effects [6][7][8][9][10][11][12] even when used for an extended period. 13,14 Terlipressin has optimal applicability, does not require specialized staff or sophisticated equipment, and is the only drug shown to improve survival from variceal bleeding in placebocontrolled trials 9,15 and meta-analyses.…”

“…The sample size calculation was based on the results of 10 published studies for terlipressin and 15 for emergency sclerotherapy (at the time the study was planned). The estimated overall failure rate for terlipressin was 40% (failure to control bleeding 20% ϩ development of early rebleeding 20%), [6][7][8][9][10][11][12][13]15,16 and 30% (10% ϩ 20%, respectively) for sclerotherapy. 3,14,[17][18][19] The sample size needed to detect clinical equivalence (a difference lower than the maximum expected, was established at 10%) in efficacy was calculated as 83 patients on each arm using a 2-sided test with 80% power at a significance level of 5%.…”

Effects of F-180, a new selective vasoconstrictor peptide, compared with terlipressin and vasopressin on systemic and splanchnic hemodynamics in a rat model of portal hypertension

“…14 Placebo-controlled trials have shown that TP is effective in controlling variceal bleeding and, more importantly, in reducing the mortality from variceal hemorrhage. [15][16][17][18] Additional randomized, controlled studies have further shown that TP is more effective and safer than VP (alone or combined with nitroglycerin), 19,20 and may prevent early rebleeding when administered for prolonged periods. 21 To date, TP is the only agent to have a significant effect on mortality from variceal hemorrhage.…”

Practical Aproach to Variceal Gastrointestinal Bleeding – Association of Polish Surgeons Guidelines

“…After this time, if the bleeding is controlled, the dosage should be reduced by half. Five days of dosing should not be exceeded (31,32,33).…”