Variceal Bleeding, Cirrhosis
Conditions
Keywords
Cirrhosis, Esophagus Disorders, Varicose Veins
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.
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.
Interventions
DRUGTerlipressin
loading with 2 mg IV, and then 1 mg IV every 4 hours for 5 days
DRUGSomatostatin
loading with 250 microgram IV, and then 250 microgram/hour continuous IV for 5 days
DRUGOctreotide
loading with 50 microgram IV, and then 25 microgram/hour continuous IV for 5 days
Sponsors
Korea University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 5-day Treatment Failure (Failure to Control Bleeding, Rebleeding, or Death) | 5 days after enrollment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
South Korea
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Octreotide 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 | 260 |
| Somatostatin 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 | 259 |
| Terlipressin 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 | 261 |
| Total | 780 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 4 | 3 |
| Overall Study | newly diagnosed advanced HCC | 11 | 12 | 10 |
| Overall Study | non-variceal bleeding on endoscopy | 68 | 70 | 71 |
Baseline characteristics
| Characteristic | Somatostatin | Terlipressin | Octreotide | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 41 Participants | 38 Participants | 40 Participants | 119 Participants |
| Age, Categorical Between 18 and 65 years | 218 Participants | 223 Participants | 220 Participants | 661 Participants |
| Age, Continuous | 53.1 years STANDARD_DEVIATION 9.7 | 52.9 years STANDARD_DEVIATION 9.2 | 53.8 years STANDARD_DEVIATION 10 | 53.3 years STANDARD_DEVIATION 9.6 |
| Region of Enrollment Korea, Republic of | 259 participants | 261 participants | 260 participants | 780 participants |
| Sex: Female, Male Female | 43 Participants | 38 Participants | 33 Participants | 114 Participants |
| Sex: Female, Male Male | 216 Participants | 223 Participants | 227 Participants | 666 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 260 | 3 / 259 | 4 / 261 |
| serious Total, serious adverse events | 0 / 260 | 0 / 259 | 0 / 261 |
Outcome results
Primary
5-day Treatment Failure (Failure to Control Bleeding, Rebleeding, or Death)
Time frame: 5 days after enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Octreotide | 5-day Treatment Failure (Failure to Control Bleeding, Rebleeding, or Death) | 218 participants |
| Somatostatin | 5-day Treatment Failure (Failure to Control Bleeding, Rebleeding, or Death) | 216 participants |
| Terlipressin | 5-day Treatment Failure (Failure to Control Bleeding, Rebleeding, or Death) | 225 participants |
Secondary
Active Bleeding During the First Endoscopic Exam, Needing Blood Transfusion for 5 Days, Experiencing Adverse Effects
at least one of the three criteria
Time frame: 5 days after enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Octreotide | Active Bleeding During the First Endoscopic Exam, Needing Blood Transfusion for 5 Days, Experiencing Adverse Effects | 113 participants |
| Somatostatin | Active Bleeding During the First Endoscopic Exam, Needing Blood Transfusion for 5 Days, Experiencing Adverse Effects | 115 participants |
| Terlipressin | Active Bleeding During the First Endoscopic Exam, Needing Blood Transfusion for 5 Days, Experiencing Adverse Effects | 114 participants |