A Randomized Trial of Terlipressin Plus Nitroglycerin Vs. Balloon Tamponade in the Control of Acute Variceal Hemorrhage

Abstract

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.

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%.…”

“…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%. The expected incidence of severe side effects was 4% for terlipressin [6][7][8][9][10][11][12][13]15,16 and 16% for EIS. 3,14 To detect such differences in the incidence of severe side effects (2-sided test, ␣ ϭ 0.05, ␤ ϭ 0.20), 95 patients were required in each group.…”

Management of Acute Variceal Bleeding

“…Its efficacy is similar to balloon tamponade [30], somatostatin [31], octreotide [32] or endoscopic sclerotherapy [33]. It is the only drug shown to decrease the mortality related to acute bleeding episode.…”

Pharmacological Treatment of Acute Variceal Bleeding

“…In the 4 fully published trials where drug treatment was There are 8 studies in the literature [60,62,63,[81][82][83][84][85]. However, comparing them is difficult, because of end compared with sclerotherapy [10][11][12]70], no statistical differences were observed between somatostatin/octreo-point definition.…”