Vasoactive Drugs in Real World Practice

NCT02757703 | Completed Phase 4

• 1 other identifier: VGHKS99-CT4-20
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Various vasoactive drugs are recommended to use in combination with endoscopic variceal ligation (EVL) in treating acute esophageal variceal bleeding (EVB). The efficacy and drug choice of vasoactive agents under Taiwan's National Health Insurance program remain to be validated. The aim of this prospective cohort study was to assess the efficacy of somatostatin, compared with terlipressin in cirrhotic patients who have acute EVB and received EVL and the preference of vasoactive agents in real-world clinical practice. From April 2010 through April 2015, cirrhotic patients with significant upper gastrointestinal bleeding were screened. Eligible patients with acute EVB were non-randomly assigned to receive early administration of somatostatin (group S) or terlipressin (group T) infusion, followed by EVL. A decision to use vasoactive drugs depended on the physician's favorite. In group S, somatostatin by intravenous bolus (250 μg) followed by 250 μg/hour was continued for 3 days. In group T, terlipressin was started with 2mg bolus injection and followed by 1 mg infusion every 6 hours for 3 days.

Conditions

Vasoconstrictor Choice on Acute Variceal Bleeding

Keywords

somatostatin; variceal bleeding; terlipressin

Outcome Measures

Primary Outcomes (1)

• Incidence rate of early rebleeding

  Early rebleeding was defined as variceal hemorrhage occurs from day 3 till day 42 after initial bleeding arrest. An episode of clinically significant bleeding is being defined by blood transfusion \> 2 units of packed red blood cells.

  up to 42 days

Secondary Outcomes (3)

• Incidence rate of very early rebleeding

  up to 5 days

• Incidence rate of mortality

  up to 42 days

• Percentage of participants with treatment-related adverse effects assessed by CTCAE v4.0

  up to 42 days

Study Arms (2)

somatostatin group

ACTIVE COMPARATOR

Somatostatin (Somatosan, BAG Health Care GmbH, Lich, Germany) was given by intravenous bolus (250 μg) followed by 250 μg/hour and continued for 3 days in group S.

Drug: Somatostatin; Drug: Pantoprazole; Device: Endoscopic variceal ligation

terlipressin group

PLACEBO COMPARATOR

Terlipressin (Glypressin, Ferring GmbH, Kiel, Germany) was started at 2mg bolus injection and followed by 1 mg infusion every 6 hours for 3 days in group T.

Drug: Terlipressin; Drug: Pantoprazole; Device: Endoscopic variceal ligation

Interventions

Somatostatin DRUG

A decision to use vasoactive drugs (either somatostatin or terlipressin) depended on the favorite of participating attending physicians who were requested to fill out the enclosed questionnaires immediately after the administration of the first dose for further understanding the underlying reason of the chosen medication.

Also known as: somatostatin infusion

somatostatin group

Terlipressin DRUG

A decision to use vasoactive drugs (either somatostatin or terlipressin) depended on the favorite of participating attending physicians who were requested to fill out the enclosed questionnaires immediately after the administration of the first dose for further understanding the underlying reason of the chosen medication.

Also known as: terlipressin infusion

terlipressin group

Pantoprazole DRUG

Both study groups were administered with 40mg pantoprazole intravenously after EVL for 3 days, and following oral form for 12 days to hasten the process of healing of ulcers induced by ligation.

Also known as: pantoprazole therapy

somatostatin group; terlipressin group

Endoscopic variceal ligation DEVICE

Two experienced endoscopists performed emergent EVL for the enrolled patients with acute EVB. Pneumoactive ligation device (Sumitomo Bakelite Co., Ltd, Tokyo, Japan) and endoscopes (GIF XQ260; Olympus Co. Ltd, Tokyo, Japan) were applied. The targeted varix was suctioned and entrapped by a cap on endoscope. Ligation was aimed at active bleeding sites, red color spots or white nipple signs during the procedure.

Also known as: EVL therapy

somatostatin group; terlipressin group

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• acute hemorrhage from esophageal varice(s)
• portal hypertension attributed by cirrhosis
• age was between 20 and 80 years old

You may not qualify if:

• being associated with hepatocellular carcinoma (HCC) of Barcelona-Clinic Liver Cancer (BCLC) \> C
• being associated with severe illness such as chronic obstructive pulmonary disease (COPD), septic shock, cerebral vascular event, acute coronary syndrome and uremia
• with current gastric variceal bleeding
• ever underwent endoscopic injection sclerotherapy (EIS), EVL within 6 month prior to current bleeding episode
• ever received shunt or transjugular intrahepatic porto-systemic stent shunt (TIPS) procedure
• allergic to and/or with contraindications of vasopressors
• pregnancy.

Sponsors & Collaborators

• Kaohsiung Veterans General Hospital.: lead

Study Sites (1)

Division of Gastroenterology, Department of Internal Medicine

Kaohsiung City, 81362, Taiwan

Location

Related Publications (6)

• GARCEAU AJ, CHALMERS TC. The natural history of cirrhosis. I. Survival with esophageal varices. N Engl J Med. 1963 Feb 28;268:469-73. doi: 10.1056/NEJM196302282680905. No abstract available.

  PMID: 13946478 BACKGROUND

• Graham DY, Smith JL. The course of patients after variceal hemorrhage. Gastroenterology. 1981 Apr;80(4):800-9.

  PMID: 6970703 BACKGROUND

• Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W; Practice Guidelines Committee of the American Association for the Study of Liver Diseases; Practice Parameters Committee of the American College of Gastroenterology. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007 Sep;46(3):922-38. doi: 10.1002/hep.21907. No abstract available.

  PMID: 17879356 BACKGROUND

• de Franchis R. Evolving consensus in portal hypertension. Report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol. 2005 Jul;43(1):167-76. doi: 10.1016/j.jhep.2005.05.009. No abstract available.

  PMID: 15925423 BACKGROUND

• 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. Hepatol Res. 2015 Dec;45(13):1276-82. doi: 10.1111/hepr.12503. Epub 2015 Apr 6.

  PMID: 25676742 BACKGROUND

• Rengasamy S, Ali SM, Sistla SC, Lakshmi CP, Harichandra Kumar KT. Comparison of 2 days versus 5 days of octreotide infusion along with endoscopic therapy in preventing early rebleed from esophageal varices: a randomized clinical study. Eur J Gastroenterol Hepatol. 2015 Apr;27(4):386-92. doi: 10.1097/MEG.0000000000000300.

  PMID: 25874510 BACKGROUND

MeSH Terms

Interventions

Somatostatin; Terlipressin; Pantoprazole

Intervention Hierarchy (Ancestors)

Pituitary Hormone Release Inhibiting Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pancreatic Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins; Lypressin; Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Oligopeptides; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Jin-Shiung Cheng, MD

  Kaohsiung Veterans General Hospital.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Division of Gastroenterology and Hepatology

Study Record Dates

• First Submitted: April 16, 2016
• First Posted: May 2, 2016
• Study Start: May 1, 2010
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: May 3, 2016

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)