Terlipressin Infusion in Variceal Hemorrhage

NCT04028505 | Unknown Phase 3 DMC

• 1 other identifier: 5209-Med-ERC-18
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Terlipressin Adverse Reaction

Keywords

Terlipressin Drug; Continuous Infusion; Bolus Form

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (3)

• Out of hospital mortality assessed through telephonic interviews from patient's caregiver

  5 weeks after being discharged from the hospital

• Failure to control bleeding as assessed by physiological parameters in the blood

  5 weeks after being discharged from the hospital

• Prolong hospital stay (> 5 days) as assessed through medical records and pre-designed questionnaire

  5 days after admission till being discharged from the hospital

Study Arms (2)

Terlipressin Continuous Infusion

EXPERIMENTAL

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

Terlipressin Bolus Infusion

ACTIVE COMPARATOR

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

Interventions

Terlipressin Injectable Product DRUG

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.

Also known as: Novapressin

Terlipressin Bolus Infusion; Terlipressin Continuous Infusion

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Aga Khan University: lead
• Mallinckrodt: collaborator

Study Sites (1)

Aga Khan University Hospital

Karachi, Sindh, 74000, Pakistan

RECRUITING

Study Officials

• Shahab Abid, PhD,FRCP

  Aga Khan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shahab Abid, Phd,FRCP

CONTACT

+92213486; shahab.abid@aku.edu

Adeel Khoja, MBBS,MSc

CONTACT

+92213486; adeel.khoja@aku.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Head Section of Gastroenterology, Department of Medicine

Model Details: Experimental Arm: Standard of care being given at AKUH + Continuous infusion of Terlipressin at a rate of 0.5mg/hour for the first 24 hours Comparator Arm: Standard of care being given at AKUH + Bolus infusion of Terlipressin at a frequency of 2mg every six hourly for first 24 hours

Study Record Dates

• First Submitted: May 10, 2018
• First Posted: July 22, 2019
• Study Start: October 25, 2018
• Primary Completion: April 25, 2020
• Study Completion: October 25, 2020
• Last Updated: July 22, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)