Terlipressin Infusion in Variceal Hemorrhage (TT)

Terlipressin Bolus Versus Continuous Infusion in Patients With Variceal Hemorrhage

Randomized, open label study of intravenous terlipressin infusion vs. bolus for the treatment of variceal hemorrhage. 24 hour regimen consisting of intravenous terlipressin will be used either at a rate of 0.5mg/hour or 2mg bolus every 4 hourly. Participants will be randomized into intervention and control arm using block randomization by computer generated random numbers. Efficacy will be assessed by clinical improvement in symptoms and signs of GI bleed. To assess safety, frequency and degree of adverse reactions will be observed. Periodic assessments until 5 days will be done consisting of physical examination, safety assessments, vital signs and lab tests.

Study Overview

• Status: Unknown
• Conditions: Terlipressin Adverse Reaction
• Intervention / Treatment: Drug: Terlipressin Injectable Product

Detailed Description

Randomized, open label trial, conducted on patients admitted with acute variceal hemorrhage at The Aga Khan University Hospital, Karachi (AKUH). Patients will be followed in clinic after discharge to assess survival for 6 weeks.

Intravenous terlipressin will be obtained from Clinical Trials Unit, AKUH pharmacy in standard IV infusion form. Following complete clinical and laboratory evaluation, assessing the patient for eligibility, informed consent will be obtained from all the participants who are willing to be part of this study. After obtaining the informed consent, study participants will be randomized into the intervention arm (continuous infusion of Terlipressin) or the control arm (bolus form of Terlipressin). Participants who are randomized to the intervention arm will be administered a continuous infusion of Terlipressin at a rate of 0.5mg/hour for the first 24 hours. Participants randomized into the control group will be administered a bolus form of Terlipressin at a rate of 2mg every six hourly for the first 24 hours respectively. In case of weekends/public holidays intravenous terlipressin will be obtained from the main pharmacy of AKUH.

The trial will be conducted in in-patient units of AKUH where eligible patients are admitted. It may include emergency room, special care unit and general ward. Moreover, patients will be followed up by phone calls and in outpatient's clinics to assess survival six weeks post discharge.

• Study Type: Interventional
• Enrollment (Anticipated): 128
• Phase: Phase 3

Contacts and Locations

Study Locations

• Pakistan
  • Sindh
    • Karachi, Sindh, Pakistan, 74000
      • Recruiting
      • Aga Khan University Hospital
      • Contact: Dilshad Begum, MScN; Phone Number: 2303 +92213486; Email: dilshad.begum@aku.edu
      • Principal Investigator: shahab Abid, Phd,FRCP
      • Sub-Investigator: Adeel Khoja, MBBS,MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age between 18 to 60 years
2. Either gender
3. A diagnosis of liver cirrhosis;
4. Initial presentation with acute gastroesophageal variceal bleeding
5. Willing to provide informed consent to participate in the study (by study subject or next of kin)

Exclusion Criteria:

1. Age < 18 or > 60 years
2. Not willing to provide consent due to any reason
3. No liver cirrhosis
4. Acute upper gastrointestinal bleeding unrelated to varices;
5. Use of somatostatin or octreotide.
6. Hepatocellular Carcinoma (HCC)outside Milan's criteria
7. Advance cardiovascular, pulmonary or renal disease (e.g. asthma, hypertension, arrhythmia, renal insufficiency)
8. History of hypersensitivity to Terlipressin
9. Pregnancy
10. Patients already admitted at AKUH who develop upper GI bleed during admission.

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: Terlipressin Continuous Infusion; Standard of care being given at AKUH + Continuous infusion of Terlipressin (Terlipressin Injectable Product) at a rate of 0.5mg/hour for the first 24 hours	Drug: Terlipressin Injectable Product; Intravenous terlipressin will be obtained from Clinical Trials Unit, AKUH pharmacy in standard IV infusion form. Participants who are randomized to the intervention arm will be administered a continuous infusion of Terlipressin at a rate of 0.5mg/hour for the first 24 hours. Participants randomized into the control group will be administered a bolus form of Terlipressin at a rate of 2mg every six hourly for the first 24 hours respectively. In case of weekends/public holidays intravenous terlipressin will be obtained from the main pharmacy of AKUH.; Other Names: Novapressin
Active Comparator: Terlipressin Bolus Infusion; Standard of care being given at AKUH + Bolus infusion of Terlipressin (Terlipressin Injectable Product) at a frequency of 2mg every six hourly for first 24 hours	Drug: Terlipressin Injectable Product; Intravenous terlipressin will be obtained from Clinical Trials Unit, AKUH pharmacy in standard IV infusion form. Participants who are randomized to the intervention arm will be administered a continuous infusion of Terlipressin at a rate of 0.5mg/hour for the first 24 hours. Participants randomized into the control group will be administered a bolus form of Terlipressin at a rate of 2mg every six hourly for the first 24 hours respectively. In case of weekends/public holidays intravenous terlipressin will be obtained from the main pharmacy of AKUH.; Other Names: Novapressin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in tachycardia, measured through heart rate (>100 bpm) being displayed in the electronic monitors in wards, emergency room and out-patient clinics	It will be assessed by trained research coordinator as; the number of study participants with 20% reduction in tachycardia as compared to the baseline between the two arms.	6 weeks (Overall length of follow-up)
Improvement in mean arterial pressure, being displayed in the electronic monitors in wards, emergency room and out-patient clinics	It will be assessed by trained research coordinator as; the number of study participants with 20% improvement in mean arterial pressure as compared to the baseline between the two arms. Adverse events related to terlipressin, such as hyponatremia, diarrhea, abdominal pain; arterial hypertension should be reported to the primary gastroenterologist between the two arms.	6 weeks (Overall length of follow-up)
In-patient hospital mortality, assessed through medical records.	It will be assessed through medical records, by a trained research coordinator as the number of study participants dying within the hospital between the two arms.	Admission of patient till death in the hospital
Failure to control bleeding as assessed by physiological parameters in the blood	It will be assessed by a trained research coordinator as the number of participants having fresh hematemesis and 3 gm drop in hemoglobin (9% drop in hematocrit) within a 24 hours' time period between the two arms.	Admission of patient till discharge from the hospital
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)	It will be assessed by trained research coordinator as; the number of participants having experienced any adverse events such as hyponatremia, diarrhea, abdominal pain, arterial hypertension, 5 days after having terlipressin drug, between the two arms.	6 weeks (Overall length of follow-up)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Out of hospital mortality assessed through telephonic interviews from patient's caregiver	It will be assessed by trained research coordinator as; the number of participants dying after being discharged from the hospital between the two arms within the follow-up time period of the study.	5 weeks after being discharged from the hospital
Failure to control bleeding as assessed by physiological parameters in the blood	It will be assessed by trained research coordinator as the number of participants having fresh hematemesis and 3 gm drop in hemoglobin (9% drop in hematocrit) after being discharged from the hospital till three subsequent follow-up visits between the two arms.	5 weeks after being discharged from the hospital
Prolong hospital stay (> 5 days) as assessed through medical records and pre-designed questionnaire	It will be assessed by trained research coordinator as; the number of participants having stayed in the hospital for more than five days between the two arms.	5 days after admission till being discharged from the hospital

Collaborators and Investigators

• Sponsor: Aga Khan University
• Collaborators: Mallinckrodt
• Investigators: Principal Investigator: Shahab Abid, PhD,FRCP, Aga Khan University

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2018
• Primary Completion (Anticipated): April 25, 2020
• Study Completion (Anticipated): October 25, 2020

Study Registration Dates

• First Submitted: May 10, 2018
• First Submitted That Met QC Criteria: July 19, 2019
• First Posted (Actual): July 22, 2019

Study Record Updates

• Last Update Posted (Actual): July 22, 2019
• Last Update Submitted That Met QC Criteria: July 19, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Terlipressin Drug; Continuous Infusion; Bolus Form
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Antihypertensive Agents; Vasoconstrictor Agents; Terlipressin
• Other Study ID Numbers: 5209-Med-ERC-18

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
• product manufactured in and exported from the U.S.: No