Efficacy of Terlipressin Therapy in Acute Variceal Haemorrhage After EVL

Study Overview
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Brief Summary
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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.

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

Conditions
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Acute Variceal Haemorrhage

Intervention / Treatment
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* Drug: Normal Saline
* Drug: Terlipressin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: TG 0 (0Hr)<br>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<br>* TG 0 (0Hr)<br>|
| Active Comparator: TG 2 (48Hr)<br>TG2 will receive Terlipressin (1mg, i.v. Bolus q 4 hourly) therapy for 48 hours after EVL . | Drug: Terlipressin<br>* Duration of Terlipressin after EVL<br>|
| Active Comparator: TG 5 (120Hr)<br>TG5 will receive Terlipressin (1mg, i.v. Bolus q 4 hourly) therapy for 120 hours after EVL . | Drug: Terlipressin<br>* Duration of Terlipressin after EVL<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Terlipressin, Variceal Haemorrhage, EVL