Comparison of 1-day versus 3-day intravenous terlipressin in cirrhosis patients with variceal bleeding: A pilot randomised controlled trial.
Journal
Alimentary pharmacology & therapeutics
ISSN: 1365-2036
Titre abrégé: Aliment Pharmacol Ther
Pays: England
ID NLM: 8707234
Informations de publication
Date de publication:
07 Jan 2024
07 Jan 2024
Historique:
revised:
18
10
2023
received:
24
09
2023
accepted:
24
12
2023
medline:
8
1
2024
pubmed:
8
1
2024
entrez:
8
1
2024
Statut:
aheadofprint
Résumé
In cirrhosis patients with acute variceal bleeding (AVB), the optimal duration of vasoconstrictor therapy after endoscopic haemostasis is unclear. We aimed to compare efficacy of 1-day versus 3-day terlipressin therapy in cirrhosis patients with AVB post-endoscopic intervention. The primary objective was to compare rebleeding at 5 days between the two arms. Secondary objectives included rebleeding and mortality rates at 6 weeks. In this open-label, randomised controlled trial, cirrhosis patients with AVB were randomised to either 1-day or 3-day terlipressin therapy. A total of 150 cirrhosis patients with AVB were recruited to receive either 1 day (n = 75) or 3 days (n = 75) of terlipressin therapy. One patient from 1-day arm was excluded. Modified intention-to-treat analysis included 149 patients. Baseline characteristics were comparable between the two groups. Rebleeding at 5 days: 3 (4.1%; 95% confidence interval [CI]: 0.4-9.0) versus 4 (5.3%; 95% CI: 2.0-10.0), risk difference (RD) p = 0.726 and 5-day mortality rates: 1 (1.4%; 95% CI: 0-7.3) versus 1 (1.3%; 95% CI: 0.2-7.0), RD p = 0.960 were similar. Rebleeding at 42 days: 9 (12.2%; 95% CI: 7.0-20.0) versus 10 (13.3%; 95% CI: 7.0-20.0), RD p = 0.842 and mortality at 42 days: 5 (6.8%; 95% CI: 3.0-10.0) versus 4 (5.3%; 95% CI: 2.0-10.0), RD p = 0.704 were also similar. Patients in the 1-day terlipressin therapy arm experienced significantly fewer adverse effects compared with those receiving 3 days of terlipressin therapy: 28 (37.8%) versus 42 (56%), p = 0.026. Our results suggest that 1 day of terlipressin therapy is associated with similar 5-day and 42-day rebleeding rates, 42-day mortality and an overall superior safety profile compared with 3-day of terlipressin therapy. These findings require to be validated in double-blinded, larger, multiethnic and multicentre studies across the various stages of cirrhosis (CTRI/2019/10/021771).
Sections du résumé
BACKGROUND
BACKGROUND
In cirrhosis patients with acute variceal bleeding (AVB), the optimal duration of vasoconstrictor therapy after endoscopic haemostasis is unclear.
AIMS
OBJECTIVE
We aimed to compare efficacy of 1-day versus 3-day terlipressin therapy in cirrhosis patients with AVB post-endoscopic intervention. The primary objective was to compare rebleeding at 5 days between the two arms. Secondary objectives included rebleeding and mortality rates at 6 weeks.
METHODS
METHODS
In this open-label, randomised controlled trial, cirrhosis patients with AVB were randomised to either 1-day or 3-day terlipressin therapy.
RESULTS
RESULTS
A total of 150 cirrhosis patients with AVB were recruited to receive either 1 day (n = 75) or 3 days (n = 75) of terlipressin therapy. One patient from 1-day arm was excluded. Modified intention-to-treat analysis included 149 patients. Baseline characteristics were comparable between the two groups. Rebleeding at 5 days: 3 (4.1%; 95% confidence interval [CI]: 0.4-9.0) versus 4 (5.3%; 95% CI: 2.0-10.0), risk difference (RD) p = 0.726 and 5-day mortality rates: 1 (1.4%; 95% CI: 0-7.3) versus 1 (1.3%; 95% CI: 0.2-7.0), RD p = 0.960 were similar. Rebleeding at 42 days: 9 (12.2%; 95% CI: 7.0-20.0) versus 10 (13.3%; 95% CI: 7.0-20.0), RD p = 0.842 and mortality at 42 days: 5 (6.8%; 95% CI: 3.0-10.0) versus 4 (5.3%; 95% CI: 2.0-10.0), RD p = 0.704 were also similar. Patients in the 1-day terlipressin therapy arm experienced significantly fewer adverse effects compared with those receiving 3 days of terlipressin therapy: 28 (37.8%) versus 42 (56%), p = 0.026.
CONCLUSIONS
CONCLUSIONS
Our results suggest that 1 day of terlipressin therapy is associated with similar 5-day and 42-day rebleeding rates, 42-day mortality and an overall superior safety profile compared with 3-day of terlipressin therapy. These findings require to be validated in double-blinded, larger, multiethnic and multicentre studies across the various stages of cirrhosis (CTRI/2019/10/021771).
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 John Wiley & Sons Ltd.
Références
Rout G, Sharma S, Gunjan D, Kedia S, Nayak B, Shalimar. Comparison of various prognostic scores in variceal and non-variceal upper gastrointestinal bleeding: a prospective cohort study. Indian J Gastroenterol. 2019;38(2):158-166. https://doi.org/10.1007/s12664-018-0928-8
The North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices. Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices. N Engl J Med. 1988;319(15):983-989. https://doi.org/10.1056/NEJM198810133191505
Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J. Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American association for the study of liver diseases. Hepatology. 2017;65(1):310-335. https://doi.org/10.1002/hep.28906
Reverter E, Tandon P, Augustin S, Turon F, Casu S, Bastiampillai R, et al. A MELD-based model to determine risk of mortality among patients with acute variceal bleeding. Gastroenterology. 2014;146(2):412-419.e3. https://doi.org/10.1053/j.gastro.2013.10.018
Lee HH, Park JM, Han S, Park SM, Kim HY, Oh JH, et al. A simplified prognostic model to predict mortality in patients with acute variceal bleeding. Dig Liver Dis. 2018;50(3):247-253. https://doi.org/10.1016/j.dld.2017.11.006
Seo YS, Park SY, Kim MY, Kim JH, Park JY, Yim HJ, et al. Lack of difference among terlipressin, somatostatin, and octreotide in the control of acute gastroesophageal variceal hemorrhage. Hepatology. 2014;60(3):954-963. https://doi.org/10.1002/hep.27006
Augustin S, Altamirano J, González A, Dot J, Abu-Suboh M, Armengol JR, et al. Effectiveness of combined pharmacologic and ligation therapy in high-risk patients with acute esophageal variceal bleeding. Am J Gastroenterol. 2011;106(10):1787-1795. https://doi.org/10.1038/ajg.2011.173
Lo GH, Chen WC, Wang HM, Lin CK, Chan HH, Tsai WL, et al. Low-dose terlipressin plus banding ligation versus low-dose terlipressin alone in the prevention of very early rebleeding of oesophageal varices. Gut. 2009;58(9):1275-1280. https://doi.org/10.1136/gut.2008.165910
de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C, Abraldes JG, et al. Baveno VII - renewing consensus in portal hypertension. J Hepatol. 2022;76(4):959-974. https://doi.org/10.1016/j.jhep.2021.12.022
Azam Z, Hamid S, Jafri W, Salih M, Abbas Z, Abid S, et al. Short course adjuvant terlipressin in acute variceal bleeding: a randomized double blind dummy controlled trial. J Hepatol. 2012;56(4):819-824. https://doi.org/10.1016/j.jhep.2011.11.019
Lo GH, Perng DS, Chang CY, Tai CM, Wang HM, Lin HC. Controlled trial of ligation plus vasoconstrictor versus proton pump inhibitor in the control of acute esophageal variceal bleeding: prevention of early variceal rebleeding. J Gastroenterol Hepatol. 2013;28(4):684-689. https://doi.org/10.1111/jgh.12107
Chitapanarux T, Ritdamrongthum P, Leerapun A, Pisespongsa P, Thongsawat S. Three-day versus five-day somatostatin infusion combination with endoscopic variceal ligation in the prevention of early rebleeding following acute variceal hemorrhage: a randomized controlled trial: early variceal rebleeding, somatostatin. Hepatol Res. 2015;45(13):1276-1282. https://doi.org/10.1111/hepr.12503
Common Terminology Criteria for Adverse Events (CTCAE). Published online 2017.
de Franchis R. Expanding consensus in portal hypertension. J Hepatol. 2015;63(3):743-752. https://doi.org/10.1016/j.jhep.2015.05.022
Bosch J, Abraldes JG, Berzigotti A, García-Pagan JC. The clinical use of HVPG measurements in chronic liver disease. Nat Rev Gastroenterol Hepatol. 2009;6(10):573-582. https://doi.org/10.1038/nrgastro.2009.149
Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94(446):496-509. https://doi.org/10.1080/01621459.1999.10474144
Garcia-Tsao G, Abraldes JG, Rich NE, Wong VWS. AGA clinical practice update on the use of vasoactive drugs and intravenous albumin in cirrhosis: expert review. Gastroenterology. 2024;166(1):202-210. https://doi.org/10.1053/j.gastro.2023.10.016
Bañares R, Albillos A, Rincón D, Alonso S, González M, Ruiz-del-Arbol L, et al. Endoscopic treatment versus endoscopic plus pharmacologic treatment for acute variceal bleeding: a meta-analysis. Hepatology. 2002;35(3):609-615. https://doi.org/10.1053/jhep.2002.31354
Zhou X, Tripathi D, Song T, Shao L, Han B, Zhu J, et al. Terlipressin for the treatment of acute variceal bleeding: a systematic review and meta-analysis of randomized controlled trials. Medicine. 2018;97(48):e13437. https://doi.org/10.1097/MD.0000000000013437
Yeh JH, Lo GH, Huang RY, Lin CW, Wang WL, Perng DS. Short-course vasoconstrictors are adequate for esophageal variceal bleeding after endoscopic variceal ligation: a systematic review and meta-analysis. Sci Prog. 2021;104(3). https://doi.org/10.1177/00368504211031711
Wang C, Han J, Xiao L, Jin CE, Li DJ, Yang Z. Efficacy of vasopressin/terlipressin and somatostatin/octreotide for the prevention of early variceal rebleeding after the initial control of bleeding: a systematic review and meta-analysis. Hepatol Int. 2015;9(1):120-129. https://doi.org/10.1007/s12072-014-9594-9
Li B, Chen J, Zhang CQ, Wang GC, Hu JH, Luo JJ, et al. The pharmacodynamic effect of terlipressin versus high-dose octreotide in reducing hepatic venous pressure gradient: a randomized controlled trial. Ann Transl Med. 2021;9(9):793. https://doi.org/10.21037/atm-20-6774
Villanueva C, Planella M, Aracil C, López-Balaguer JM, González B, Miñana J, et al. Hemodynamic effects of terlipressin and high somatostatin dose during acute variceal bleeding in nonresponders to the usual somatostatin dose. Am J Gastroenterol. 2005;100(3):624-630. https://doi.org/10.1111/j.1572-0241.2004.40665.x
Ioannou G, Doust J, Rockey DC. Terlipressin for acute esophageal variceal hemorrhage. Cochrane Database Syst Rev. 2003;(1):CD002147. https://doi.org/10.1002/14651858.CD002147
Bañares R, Moitinho E, Piqueras B, Casado M, García-Pagán JC, de Diego A, et al. Carvedilol, a new nonselective beta-blocker with intrinsic anti-alpha1-adrenergic activity, has a greater portal hypotensive effect than propranolol in patients with cirrhosis: carvedilol, a new nonselective beta-blocker with intrinsic anti-Alpha1-adrenergic activity, has a greater portal hypotensive effect than propranolol. Hepatology. 1999;30(1):79-83. https://doi.org/10.1002/hep.510300124
Tripathi D, Therapondos G, Lui HF, Stanley AJ, Hayes PC. Haemodynamic effects of acute and chronic administration of low-dose carvedilol, a vasodilating β-blocker, in patients with cirrhosis and portal hypertension: low-dose carvedilol and portal hypertension. Aliment Pharmacol Ther. 2002;16(3):373-380. https://doi.org/10.1046/j.1365-2036.2002.01190.x
Lin HC, Yang YY, Hou MC, Huang YT, Lee FY, Lee SD. Acute Administration of Carvedilol is more effective than propranolol plus Isosorbide-5-Mononitrate in the reduction of portal pressure in patients with viral cirrhosis. Am J Gastroenterology. 2004;99(10):1953-1958. https://doi.org/10.1111/j.1572-0241.2004.40179.x
Azam Z, Hamid S, Jafri W, Salih M, Abbas Z, Abid S, et al. Short course adjuvant terlipressin in acute variceal bleeding: a randomized double blind dummy controlled trial. J Hepatol. 2012;56(4):819-824. https://doi.org/10.1016/j.jhep.2011.11.019
Arora V, Choudhary SP, Maiwall R, Vijayaraghavan R, Jindal A, Kumar G, et al. Low-dose continuous terlipressin infusion is effective and safer than intravenous bolus injections in reducing portal pressure and control of acute variceal bleeding. Hepatol Int. 2023;17(1):131-138. https://doi.org/10.1007/s12072-022-10416-6