Efficacy of Terlipressin Therapy in Acute Variceal Haemorrhage After EVL (TEVL)

Efficacy of Terlipressin Therapy in Acute Variceal Haemorrhage After Endoscopic Variceal Ligation: A Randomised Controlled Clinical Trial

Upper gastrointestinal (UGI) bleed of variceal origin is a common medical emergency. Prompt endoscopic variceal ligation (EVL) is therapeutic as well as diagnostic. Terlipressin, a vasopressin analog (intravenous, 2 mg q 4 hourly), is widely used promptly in any suspicious case of variceal haemorrhage (VH) before endoscopic procedure, along with volume and blood resuscitative measures. As per guideline, after EVL Terlipressin therapy (1 mg IV q 4 hourly) is continued for 2-5 day to prevent re-bleed. But the prolong use of Terlipressin is not completely safe as well as it is expensive also in resource constraint setting. At present there is no clinical trial available to prove the efficacy of post-EVL Terlipressin therapy in preventing re-bleed and mortality in cases of acute variceal haemorrhage. During the post marketing surveillance Terlipressin therapy has been found to be associated with life threatening complication like cardiac arrhythmia, myocardial ischemia, critical vasoconstriction of peripheral as well as internal organ leading to ischemia or gangrene, severe hyponatremia, hypertension, fluid overload and pulmonary oedema. So the justification of continuing Terlipressin therapy for 5 days after EVL is questionable, as haemostasis is primarily achieved by EVL and the risk versus benefit of Terlipressin therapy after EVL is still unknown. Continue IV Terlipressin therapy also prolongs in-hospital care causing further increase of health care burden. There is still lack of data of Terlipressin therapy, regarding its efficacy in preventing post-EVL re-bleed, mortality, adverse drug events and cost effectiveness. The investigator will study to evaluate the utility of Terlipressin therapy after EVL, in acute variceal haemorrhage.

Study Overview

• Status: Completed
• Conditions: Acute Variceal Haemorrhage
• Intervention / Treatment: Drug: Normal Saline; Drug: Terlipressin

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Chandigarh, India, 160012
    • Post Graduate Institute of Medical Education and Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Irrespective of gender with age ≥ 18 years
• All the patients with endoscopy proven acute variceal haemorrhage (VH)
• Receiving Pre-EVL Terlipressin therapy
• EVL done within 24 hours of presentation
• Ready to give written informed consent

Exclusion Criteria:

• Patients with UGI bleed for more than 24 hours
• Not receiving pre-EVL Terlipressin therapy
• Pregnancy
• Past history of EVL
• Chronic kidney disease
• Patient's with EVL done beyond 24 hours of admission because of hemodynamic instability or encephalopathy
• Patients who are receiving blood thinners like anti-platelets, anti-coagulation agents within 4 weeks of presentation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: TG 0 (0Hr); TG0 will receive 10 ml of 0.9% normal saline (NS) IV bolus q 4 hourly in place of Terlipressin therapy after EVL.	Drug: Normal Saline; TG 0 (0Hr)
Active Comparator: TG 2 (48Hr); TG2 will receive Terlipressin (1mg, i.v. Bolus q 4 hourly) therapy for 48 hours after EVL .	Drug: Terlipressin; Duration of Terlipressin after EVL
Active Comparator: TG 5 (120Hr); TG5 will receive Terlipressin (1mg, i.v. Bolus q 4 hourly) therapy for 120 hours after EVL .	Drug: Terlipressin; Duration of Terlipressin after EVL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Early-Rebleed	To evaluate the efficacy of Terlipressin therapy to prevent re-bleed after EVL in acute variceal Haemorrhage (VH)	5 days
Number of participants with Rebleed	To evaluate the efficacy of Terlipressin therapy to prevent re-bleed after EVL in acute variceal Haemorrhage (VH)	Within 2 Months
Early-Mortality	To evaluate the efficacy of Terlipressin therapy to prevent mortality after EVL in acute VH	7 days
Mortality	To evaluate the efficacy of Terlipressin therapy to prevent mortality after EVL in acute VH	Within 2 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse drug events(ADE)	To evaluate ADE associated with Terlipressin therapy	5 days
Hospital Stay	Duration of hospital Stay	Maximum 2 Months
Number of units of Blood transfusion during Hospital Stay	Number of units of Blood transfusion during Hospital Stay	In hospital maximum upto 8 weeks
Cost of therapy	Total cost of therapy during hospitalization	In hospital maximum upto 8 weeks
Complication	Hepatic encephalopathy, need for mechanical ventilation, sepsis, shock, hospital acquired Pneumonia	In hospital maximum upto 8 weeks

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research
• Investigators: Principal Investigator: Deba P Dhibar, MD, Post Graduate Institute of Medical Education and Research

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2018
• Primary Completion (Actual): July 31, 2019
• Study Completion (Actual): July 31, 2019

Study Registration Dates

• First Submitted: May 26, 2018
• First Submitted That Met QC Criteria: July 10, 2018
• First Posted (Actual): July 12, 2018

Study Record Updates

• Last Update Posted (Actual): December 16, 2019
• Last Update Submitted That Met QC Criteria: December 13, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Terlipressin, Variceal Haemorrhage, EVL
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Antihypertensive Agents; Vasoconstrictor Agents; Terlipressin
• Other Study ID Numbers: IEC/2018/000684

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