Terlypressin and endoscopic sclerotherapy control variceal bleeding and prevent early rebleeding in cirrhotic patients

Fiaccadori, F; Pedretti, Giorgio; Biraghi, M.; Arcidiacono, R

doi:10.1016/s0011-393x(05)80671-x

Cited by 20 publications

(13 citation statements)

References 25 publications

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“…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. 3 This multicenter RCT was aimed at investigating whether, in cirrhotic patients with acute variceal bleeding, prolonged therapy with terlipressin is as effective as emergency EIS in (1) controlling bleeding, (2) preventing early rebleeding, (3) survival, and (4) incidence of side effects.…”

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confidence: 99%

“…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%.…”

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“…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.…”

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

et al. 2000

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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. (HEPATOLOGY 2000;32:471-476.)Variceal bleeding complicating cirrhosis results in a high mortality (24% to 35%), mainly determined by the impairment in liver function, the failure to control bleeding, and the development of early rebleeding. 1 The high frequency of early rebleeding (30% to 50%) 2 has led to the recommendation that treatments for variceal hemorrhage should be aimed, not only at arresting bleeding, but also at preventing early rebleeding. 3 Emergency endoscopic injection sclerotherapy (EIS) is widely considered as the best treatment for variceal bleeding. 3,4 However, EIS has limitations because of the difficulties in having an experienced endoscopist on a 24-hours-a-day basis and the risk of causing severe side effects, known to be more frequent following emergency than elective procedures. 5 It is doubtful that banding ligation is better than EIS in acute bleeding. 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 6-12 even when used for an extended period. 13,14 Terlipressin has optimal applicability, does not require specialized staff or sophistic...

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

et al. 2000

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“…[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. 15,22 At the second Baveno International Consensus Meeting (Bavero, Italy, April 1990), TP was placed first of the pharmacological options for the treatment of acute bleeding varices.…”

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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

Bernadich

Bandi

Melin³

et al. 1998

Hepatology

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The present study is aimed at characterizing the portal, splanchnic, and systemic circulatory effects of F-180, a new long-acting analog of vasopressin (VP) with selective effect on the vascular (V 1 ) receptor, both in normal rats and in portal-hypertensive animals. In preliminary vasopressor tests, F-180 was 18 times more potent than terlipressin (TP) (164 ؎ 10 IU ؋ mmol ؊1 vs. 9.2 ؎ 1.2 IU ؋ mmol ؊1 ) and four times less potent than arginine VP (614 ؎ 25 IU ؋ mmol ؊1 ). F-180 had negligible antidiuretic potency, resulting in vascular selectivity (V 1 /V 2 ) of 858 compared with 1.0 for VP and 2.2 for TP. In portal-hypertensive rats with partial portal vein ligation (PPVL), the vasopressor effect of F-180 was 19 times that of TP on a molar basis (ED 50 F-180: 0.54 vs. TP: 10.02 nmol ؋ kg ؊1 ). At low doses (0.405 nmol ؋ kg ؊1 ), F-180 significantly reduced portal pressure (PP) (؊13.8% ؎ 6.7%) and superior mesenteric artery blood flow (SMABF) (؊25.6% ؎ 4.5%), whereas TP at 8.10 nmol ؋ kg ؊1 was required to achieve comparable splanchnic effects; however, this dose caused a significantly greater increase in mean arterial pressure (MAP) than F-180 at 0.405 nmol ؋ kg ؊1 (28.2% ؎ 2.7% vs. 8.9% ؎ 2.7% at 20 minutes; P F .05). F-180 at 0.405 nmol ؋ kg ؊1 had effects on PP and SMABF similar to a 30-minute intravenous infusion of VP at 10 mU ؋ kg ؊1 in PPVL rats, but VP caused a significantly greater elevation in systemic vascular resistance (SVR) and MAP, and more pronounced reduction in cardiac index (P F .05). (HEPATOLOGY 1998;27:351-356.)

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“…[9][10] However, whether it significantly reduces 6-week rebleeding or not is still unclear. 9 Aiming at reducing early rebleeding, administration of somatostatin, 11 octreotide, [12][13] or terlipressin 14 has been prolonged for as long as 5 [11][12][13] to 7 14 days after bleeding control, and ␤-blockers have been administered as soon as 24 15 to 72 hours [16][17] after bleeding cessation. However, so far none of these treatments has been shown to significantly reduce the risk of rebleeding within 6 weeks.…”

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Octreotide compared with placebo in a treatment strategy for early rebleeding in cirrhosis. A double blind, randomized pragmatic trial

et al. 1998

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␤-Blockers and sclerotherapy prevent long-term upper digestive rebleeding in cirrhosis but they seem ineffective for early rebleeding. We compared octreotide with a placebo for the prevention of early rebleeding in cirrhotic patients. After control of acute upper digestive bleeding, 262 consecutive cirrhotic patients were randomized to octreotide 100 g subcutaneously three times a day for 15 days (n ‫؍‬ 131) or to the placebo (n ‫؍‬ 131), in a double blind pragmatic trial in which ␤-blockers and/or sclerotherapy were allowed together with the experimental treatment. Separate randomization and analysis were performed according to whether patients were eligible for ␤-blockers and/or sclerotherapy (101 placebo, 97 octreotide) or not (30 placebo, 34 octreotide). Rebleeding within 15 days was the primary measure of treatment efficacy; 6-week rebleeding rate was also assessed as a secondary measure. Fifteen-day cumulative proportions of patients rebleeding were 28% in the placebo group and 24% in the octreotide group (P ‫؍‬ .40); corresponding figures among the 198 patients eligible to ␤-blockers and/or sclerotherapy were 26% and 16% (P ‫؍‬ .05) and among the 64 not eligible for these treatments 33% and 49% (P ‫؍‬ .29). Among patients eligible to ␤-blockers and/or sclerotherapy, a significant reduction of rebleeding episodes (35 vs. 18, P ‫؍‬ .03), blood transfusions (75 vs. 50, P ‫؍‬ .04), and days of stay in hospital (1,544 vs. 1,190, P ‫؍‬ .0001) was also found in the octreotide group: this beneficial effect was confirmed 6 weeks after randomization. Following upper digestive bleeding in cirrhosis, almost 50% of patients rebleed and 30% die within 6 weeks.

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Terlypressin and endoscopic sclerotherapy control variceal bleeding and prevent early rebleeding in cirrhotic patients

Cited by 20 publications

References 25 publications

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

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

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

Octreotide compared with placebo in a treatment strategy for early rebleeding in cirrhosis. A double blind, randomized pragmatic trial

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