2- Day vs. 5- Day Terlipressin and Ceftriaxone in the Control Acute Gastroesophageal Variceal Hemorrhage

A Prospective, Randomized Controlled Trial of 2- Day vs. 5- Day Terlipressin and Ceftriaxone in the Prevention of Very Early Rebleeding in Patients With Acute Gastroesophageal Variceal Hemorrhage

The use of prophylactic antibiotics in cirrhotics with gastrointestinal bleeding has been a routine clinical practice . It is still unknown whether use of short term vasoconstrictors and antibiotics could have superior acute hemostatic rate.

Thus, the investigators conducted a trial to compare the effectiveness between participants receiving terlipressin and ceftriaxone 5 days and terlipressin and ceftriaxone 2 days after endoscopic therapy in cirrhotic patients presenting with acute gastro-esophageal variceal hemorrhage..

Study Overview

• Status: Unknown
• Conditions: Variceal Rebleeding Rate and Infections
• Intervention / Treatment: Drug: Terlipressin 1Mg Powder for Conventional Release Solution for Injection Vial

Detailed Description

Acute gastro-esophageal variceal hemorrhage is a dreadful complication of portal hypertension. Meta-analysis showed that the combination of vasoconstrictor and endoscopic therapy is superior to endoscopic therapy or vasoconstrictor alone in the control of acute esophageal variceal hemorrhage. Bacterial infections are frequently encountered in cirrhotic patients presenting with acute upper gastrointestinal bleeding. The association of bacterial infections to variceal bleeding may increase the occurrence of variceal rebleeding and mortality. A study has shown that antibiotic prophylaxis in patients with acute esophageal variceal hemorrhage may reduce infection as well as prevent rebleeding. Currently, most guidelines recommend that vasoactive drugs should be continued for 3 to 5 days after endoscopic therapy and antibiotics should be instituted for up to 7 days to manage patients with acute esophageal variceal hemorrhage . On the other hand, some studies in recent years implied that short term vasoconstrictors or antibiotics could achieve similar low variceal rebleeding rates. The use of prophylactic antibiotics in cirrhotics with gastrointestinal bleeding for only one single dose or 3 days appeared to be feasible. It is still unknown whether use of short term both vasoconstrictors and antibiotics could have similar acute hemostatic rate.

Thus, the investigators conducted a trial to compare the effectiveness between participants receiving terlipressin and ceftriaxone 5 days and terlipressin and ceftriaxone 2 days after endoscopic therapy in cirrhotic patients presenting with acute gastroesophageal variceal hemorrhage..

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Gin-Ho Lo, M.D.; Phone Number: 975-106-200; Email: ghlo@kimo.com

Study Locations

• Taiwan
  • Kaohsiung, Taiwan, 824
    • Recruiting
    • E-DA Hospital
    • Contact: Gin-Ho Lo; Phone Number: 975-106-200; Email: ghlo@kimo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients were diagnosed to have cirrhosis based on history, physical examinations, image studies or histological examination..
2. Age ranges between 20-80 y/o.
3. Patients presenting with hematemesis and /or melena within 24 hours of inclusion.

4. Esophageal variceal bleeding is controlled by esophageal variceal ligation (EVL). Gastric variceal bleeding is controlled by endoscopic glue ( histoacryl) injection.

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Exclusion Criteria:

1. Uncertain of bleeding source.
2. Failure in endoscopic therapy.
3. Had variceal bleeding or peptic ulcer bleeding in recent one month
4. has evidence of bacterial infections or possible infection at entry ( such as fever > 37.5。 C, white blood cells> 10000/cumm, urine leukocytes >10/ field, pneumonic patches on chest x-ray, ascitic polymorphonuclear cells > 250/cumm, cellulitis or other focal infections).

2) ever received antibiotics within 4 weeks before index upper gastrointestinal bleeding.

3) presence of cardiopulmonary embarrassment 4) association with uremia and receiving hemodialysis or peritoneal dialysis. 5) presence of deep jaundice (serum bilirubin > 10 mg/dl), hepatic encephalopathy stage III or IV, massive or refractory ascites 6) presence of chronic kidney disease ( serum creatinine > 2 mg/dl) or hepatorenal syndrome 7) Had history of cerebrovascular accident, coronary artery disease, complete AV block or peripheral vascular disorder 6) association with human immunodeficiency virus (HIV) infection, advanced carcinoma or hepatocellular carcinoma Barcelona Club Liver Cancer (BCLC) class C or D.

7) allergy to terlipressin, cephalosporins or penicillin 8) pregnancy. 9) Uncooperative or decline to be enrolled

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; receiving terlipressin 2mg bolus on enrollment followed by 1mg per 6 hours. Both Terlipressin infusion and Ceftriaxone continue till 48 hours after endoscopic therapy	Drug: Terlipressin 1Mg Powder for Conventional Release Solution for Injection Vial; efficacy comparison between 2 days and 5 days; Other Names: Ceftriaxone 1gm
Active Comparator: Gruoup B; receiving terlipressin 2mg bolus instituted on enrollment followed by 1mg per 6 hours. Ceftriaxone 1gm intravenously dose of ceftriaxone 1gm at 24 h interval. Both Terlipressin infusion and Ceftriaxone continue till 5 days after endoscopic therapy.	Drug: Terlipressin 1Mg Powder for Conventional Release Solution for Injection Vial; efficacy comparison between 2 days and 5 days; Other Names: Ceftriaxone 1gm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of very early rebleeding	The occurrence of variceal rebleeding after initial hemostasis	5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bacterial infections, 42-day rebleeding, mortality	Incidence of bacterial infections & rebleeding, mortality in 6 weeks	6 weeks

Collaborators and Investigators

• Sponsor: E-DA Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2019
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): August 1, 2022

Study Registration Dates

• First Submitted: August 6, 2019
• First Submitted That Met QC Criteria: August 13, 2019
• First Posted (Actual): August 14, 2019

Study Record Updates

• Last Update Posted (Actual): August 14, 2019
• Last Update Submitted That Met QC Criteria: August 13, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Antihypertensive Agents; Anti-Infective Agents; Anti-Bacterial Agents; Vasoconstrictor Agents; Ceftriaxone; Terlipressin
• Other Study ID Numbers: EMRP39107N

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No