Comparison of Terlipressin, Somatostatin, and Octreotide for Control of Variceal Bleeding

• Sponsor: Korea University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00966355
• Collaborator: (none)
• Enrollment: 1,034
• Location: 1
• Arms: 3
• Duration (Months): 44
• Patients Per Site Per Month: 23.5

Study Details

Study Description

Brief Summary

This study is performed to compare the efficacy of terlipressin, somatostatin, and octreotide in patients with variceal bleeding for the control of variceal bleeding in combination with endoscopic therapy.

Condition or Disease	Intervention/Treatment	Phase
Variceal Bleeding, Cirrhosis	Drug: Terlipressin; Drug: Somatostatin; Drug: Octreotide	Phase 4

Detailed Description

In patients who are suspected to have variceal bleedings, pharmacologic therapy with vasoactive drugs such as terlipressin, somatostatin, and octreotide is recommended as soon as possible, even before endoscopy. However, it is still unclear whether the efficacies of these drugs are same or not. This study is performed to compare the efficacy of terlipressin, somatostatin, and octreotide in patients with variceal bleeding for the control of variceal bleeding in combination with endoscopic therapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1034 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: RCT for the Effect of Early Administration of Vasoactive Substances When Combined With Endoscopic Treatment in Acute Gastro-esophageal Variceal Bleeds: Comparisons Among Terlipressin, Somatostatin, and Octreotide
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Terlipressin treat with terlipressin IV for 5 days and endoscopic treatment	Drug: Terlipressin; loading with 2 mg IV, and then 1 mg IV every 4 hours for 5 days; Other Names: Glypressin
Active Comparator: Somatostatin treat with somatostatin IV for 5 days and endoscopic treatment	Drug: Somatostatin; loading with 250 microgram IV, and then 250 microgram/hour continuous IV for 5 days; Other Names: Somatosan
Active Comparator: Octreotide treat with octreotide IV for 5 days and endoscopic treatment	Drug: Octreotide; loading with 50 microgram IV, and then 25 microgram/hour continuous IV for 5 days; Other Names: Sandostatin

Outcome Measures

Primary Outcome Measures

1. 5-day Treatment Failure (Failure to Control Bleeding, Rebleeding, or Death) [5 days after enrollment]

Secondary Outcome Measures

1. Active Bleeding During the First Endoscopic Exam, Needing Blood Transfusion for 5 Days, Experiencing Adverse Effects [5 days after enrollment]

   at least one of the three criteria

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• liver cirrhosis

• age between 16 and 75 years

• Patients who have upper GI bleeding symptoms (hematemesis or melena) within 24 hours before enrollment

• Patients whose systolic blood pressure <100 mmHg or pulse rate >100/min at the enrollment

• Patients who were not performed endoscopic or pharmacologic therapy for varices

• Signed informed consent

Exclusion Criteria:

• Pregnancy

• Positive anti-HIV Ab

• A history of severe side-effects or contraindications to study drugs

• Severe cardiovascular diseases: acute myocardial infarction, A-V block, congestive heart failure, ischemic heart disease, hypertension (systolic blood pressure >170 mmHg or diastolic pressure >100 mmHg)

• Chronic renal failure

• Hepatocellular carcinoma with protal vein thrombosis

• Coexisting malignancy except hepatocellular carcinoma

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Korea University Anam Hospital	Seoul		Korea, Republic of	136-705

Sponsors and Collaborators

• Korea University

Investigators

• Principal Investigator: Soon Ho Um, Prof, Korea University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Soon Ho Um, Professor, Korea University
• ClinicalTrials.gov Identifier: NCT00966355
• Other Study ID Numbers: TPSTOT
• First Posted: Aug 26, 2009
• Last Update Posted: Mar 19, 2018
• Last Verified: Aug 1, 2017

• Keywords provided by Soon Ho Um, Professor, Korea University: Cirrhosis, Esophagus Disorders, Varicose Veins
• Additional relevant MeSH terms: Hemorrhage; Fibrosis; Octreotide; Terlipressin; Somatostatin

Study Results

Participant Flow

Recruitment Details	Patients with liver cirrhosis presenting with either hematemesis or melena between October 1, 2006 and May 31, 2010 at eleven medical centers distributed throughout Korea.
Pre-assignment Detail	failure to fulfill inclusion criteria, no cirrhosis, prior endoscopic therapy within 2 weeks, enrolled within 6 weeks before index bleed, severe cardiovascular diseases, chronic renal failure, hepatocellular carcinoma invading portal vein, other malignancy, pregnancy, HIV-positive, hypersensitivity to the study drugs, or refusal to participate.

Arm/Group Title	Octreotide	Somatostatin	Terlipressin
Arm/Group Description	treat with octreotide IV for 5 days and endoscopic treatment Octreotide : loading with 50 microgram IV, and then 25 microgram/hour continuous IV for 5 days	treat with somatostatin IV for 5 days and endoscopic treatment Somatostatin : loading with 250 microgram IV, and then 250 microgram/hour continuous IV for 5 days	treat with terlipressin IV for 5 days and endoscopic treatment Terlipressin : loading with 2 mg IV, and then 1 mg IV every 4 hours for 5 days
Period Title: Overall Study
STARTED	344	345	345
COMPLETED	260	259	261
NOT COMPLETED	84	86	84

Baseline Characteristics

Arm/Group Title	Octreotide	Somatostatin	Terlipressin	Total
Arm/Group Description	treat with octreotide IV for 5 days and endoscopic treatment Octreotide : loading with 50 microgram IV, and then 25 microgram/hour continuous IV for 5 days	treat with somatostatin IV for 5 days and endoscopic treatment Somatostatin : loading with 250 microgram IV, and then 250 microgram/hour continuous IV for 5 days	treat with terlipressin IV for 5 days and endoscopic treatment Terlipressin : loading with 2 mg IV, and then 1 mg IV every 4 hours for 5 days	Total of all reporting groups
Overall Participants	260	259	261	780
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	220 84.6%	218 84.2%	223 85.4%	661 84.7%
>=65 years	40 15.4%	41 15.8%	38 14.6%	119 15.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.8 (10.0)	53.1 (9.7)	52.9 (9.2)	53.3 (9.6)
Sex: Female, Male (Count of Participants)
Female	33 12.7%	43 16.6%	38 14.6%	114 14.6%
Male	227 87.3%	216 83.4%	223 85.4%	666 85.4%
Region of Enrollment (participants) [Number]
Korea, Republic of	260 100%	259 100%	261 100%	780 100%

Outcome Measures

1. Primary Outcome

Title	5-day Treatment Failure (Failure to Control Bleeding, Rebleeding, or Death)
Time Frame	5 days after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Octreotide	Somatostatin	Terlipressin
Arm/Group Description	treat with octreotide IV for 5 days and endoscopic treatment Octreotide : loading with 50 microgram IV, and then 25 microgram/hour continuous IV for 5 days	treat with somatostatin IV for 5 days and endoscopic treatment Somatostatin : loading with 250 microgram IV, and then 250 microgram/hour continuous IV for 5 days	treat with terlipressin IV for 5 days and endoscopic treatment Terlipressin : loading with 2 mg IV, and then 1 mg IV every 4 hours for 5 days
Measure Participants	260	259	261
Number [participants]	218 83.8%	216 83.4%	225 86.2%

2. Secondary Outcome

Title	Active Bleeding During the First Endoscopic Exam, Needing Blood Transfusion for 5 Days, Experiencing Adverse Effects
Description	at least one of the three criteria
Time Frame	5 days after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Octreotide	Somatostatin	Terlipressin
Arm/Group Description	treat with octreotide IV for 5 days and endoscopic treatment Octreotide : loading with 50 microgram IV, and then 25 microgram/hour continuous IV for 5 days	treat with somatostatin IV for 5 days and endoscopic treatment Somatostatin : loading with 250 microgram IV, and then 250 microgram/hour continuous IV for 5 days	treat with terlipressin IV for 5 days and endoscopic treatment Terlipressin : loading with 2 mg IV, and then 1 mg IV every 4 hours for 5 days
Measure Participants	260	259	261
Number [participants]	113 43.5%	115 44.4%	114 43.7%

Adverse Events

Arm/Group Title	Octreotide		Somatostatin		Terlipressin
Arm/Group Description	treat with octreotide IV for 5 days and endoscopic treatment Octreotide : loading with 50 microgram IV, and then 25 microgram/hour continuous IV for 5 days		treat with somatostatin IV for 5 days and endoscopic treatment Somatostatin : loading with 250 microgram IV, and then 250 microgram/hour continuous IV for 5 days		treat with terlipressin IV for 5 days and endoscopic treatment Terlipressin : loading with 2 mg IV, and then 1 mg IV every 4 hours for 5 days
All Cause Mortality
	Octreotide		Somatostatin		Terlipressin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Octreotide		Somatostatin		Terlipressin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/260 (0%)		0/259 (0%)		0/261 (0%)
Other (Not Including Serious) Adverse Events
	Octreotide		Somatostatin		Terlipressin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/260 (1.2%)		3/259 (1.2%)		4/261 (1.5%)
Gastrointestinal disorders
diarrhea	3/260 (1.2%)	3	3/259 (1.2%)	3	4/261 (1.5%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.